Cancer development is frequently associated with dysregulation of mRNA translation to enhance both increased global protein synthesis and translation of specific mRNAs encoding oncoproteins. Thus, targeted inhibition of mRNA translation is viewed as a promising new approach for cancer therapy. In this article we review current progress in investigating dysregulation of mRNA translation initiation in mature B-cell neoplasms, focusing on chronic lymphocytic leukemia, follicular lymphoma and diffuse large B-cell lymphoma. We discuss mechanisms and regulation of mRNA translation, potential pathways by which genetic alterations and the tumor microenvironment alters mRNA translation in malignant B cells, preclinical evaluation of drugs targeted against specific eukaryotic initiation factors and current progress towards clinical development. Overall, inhibition of mRNA translation initiation factors is an exciting and promising area for development of novel targeted anti-tumor drugs.
[Names] => Joe Taylor ... Graham Packham [Doi] => 10.37349/etat.2020.00002 [Published] => February 29, 2020 [Viewed] => 5121 [Downloaded] => 116 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00002 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:3–25 [Recommend] => 0 [Keywords] => mRNA translation, initiation, lymphoma, leukemia, inhibitor, drug [DetailTitle] => [DetailUrl] => [Id] => 10022 [ris] => https://www.explorationpub.com/uploads/Article/A10022/8e296ffa62ee11f31d82e33243378bec.ris [bib] => https://www.explorationpub.com/uploads/Article/A10022/4fa5f09fa641897946924dd01f9bad7c.bib [ens] => [Cited] => 7 [Cited_Time] => 2024-04-27 [CitethisArticle] => Taylor J, Yeomans AM, Packham G. Targeted inhibition of mRNA translation initiation factors as a novel therapeutic strategy for mature B-cell neoplasms. Explor Target Antitumor Ther. 2020;1:3-25. https://doi.org/10.37349/etat.2020.00002 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Targeted inhibition of mRNA translation initiation factors as a novel therapeutic strategy for mature B-cell neoplasms, mRNA translation, initiation, lymphoma, leukemia, inhibitor, drug, Cancer development is frequently associated with dysregulation of mRNA translation to enhance both increased global protein synthesis and translation of specific mRNAs encoding oncoproteins. Thus, targeted inhibition of mRNA translation is viewed as a promising new approach for cancer therapy. In this article we review current progress in investigating dysregulation of mRNA translation initiation in mature B-cell neoplasms, focusing on chronic lymphocytic leukemia, follicular lymphoma and diffuse large B-cell lymphoma. We discuss mechanisms and regulation of mRNA translation, potential pathways by which genetic alterations and the tumor microenvironment alters mRNA translation in malignant B cells, preclinical evaluation of drugs targeted against specific eukaryotic initiation factors and current progress towards clinical development. Overall, inhibition of mRNA translation initiation factors is an exciting and promising area for development of novel targeted anti-tumor drugs. ,Joe Taylor ... Graham Packham [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [2] => Array ( [ArticleId] => 3 [Create_Time] => 2020-02-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202010/20201027054905.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A10023/10023.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A10023/10023.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A10023/10023_cover.png [JournalsId] => 4 [Title] => Inhibitors of the Fanconi anaemia pathway as potential antitumour agents for ovarian cancer [Abstract] => The Fanconi anaemia (FA) pathway is an important mechanism for cellular DNA damage repair, which functions to remove toxic DNA interstrand crosslinks. This is particularly relevant in the context of [AbstractComplete] =>The Fanconi anaemia (FA) pathway is an important mechanism for cellular DNA damage repair, which functions to remove toxic DNA interstrand crosslinks. This is particularly relevant in the context of ovarian and other cancers which rely extensively on interstrand cross-link generating platinum chemotherapy as standard of care treatment. These cancers often respond well to initial treatment, but reoccur with resistant disease and upregulation of DNA damage repair pathways. The FA pathway is therefore of great interest as a target for therapies that aim to improve the efficacy of platinum chemotherapies, and reverse tumour resistance to these. In this review, we discuss recent advances in understanding the mechanism of interstrand cross-link repair by the FA pathway, and the potential of the component parts as targets for therapeutic agents. We then focus on the current state of play of inhibitor development, covering both the characterisation of broad spectrum inhibitors and high throughput screening approaches to identify novel small molecule inhibitors. We also consider synthetic lethality between the FA pathway and other DNA damage repair pathways as a therapeutic approach.
[Names] => Sarah J Taylor ... Simon P Langdon [Doi] => 10.37349/etat.2020.00003 [Published] => February 29, 2020 [Viewed] => 6341 [Downloaded] => 181 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00003 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:26–52 [Recommend] => 0 [Keywords] => Fanconi anaemia protein, ovarian cancer, carboplatin, cisplatin, inhibitors, DNA repair [DetailTitle] => [DetailUrl] => [Id] => 10023 [ris] => https://www.explorationpub.com/uploads/Article/A10023/1480edaf41d6dc193af1b93ad5aabc3d.ris [bib] => https://www.explorationpub.com/uploads/Article/A10023/a0d176861d83a2fd809c0cd0cf90c41d.bib [ens] => [Cited] => 0 [Cited_Time] => 2021-02-01 [CitethisArticle] => Taylor SJ, Arends MJ, Langdon SP. Inhibitors of the Fanconi anaemia pathway as potential antitumour agents for ovarian cancer. Explor Target Antitumor Ther. 2020;1:26-52. https://doi.org/10.37349/etat.2020.00003 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Inhibitors of the Fanconi anaemia pathway as potential antitumour agents for ovarian cancer, Fanconi anaemia protein, ovarian cancer, carboplatin, cisplatin, inhibitors, DNA repair, The Fanconi anaemia (FA) pathway is an important mechanism for cellular DNA damage repair, which functions to remove toxic DNA interstrand crosslinks. This is particularly relevant in the context of ovarian and other cancers which rely extensively on interstrand cross-link generating platinum chemotherapy as standard of care treatment. These cancers often respond well to initial treatment, but reoccur with resistant disease and upregulation of DNA damage repair pathways. The FA pathway is therefore of great interest as a target for therapies that aim to improve the efficacy of platinum chemotherapies, and reverse tumour resistance to these. In this review, we discuss recent advances in understanding the mechanism of interstrand cross-link repair by the FA pathway, and the potential of the component parts as targets for therapeutic agents. We then focus on the current state of play of inhibitor development, covering both the characterisation of broad spectrum inhibitors and high throughput screening approaches to identify novel small molecule inhibitors. We also consider synthetic lethality between the FA pathway and other DNA damage repair pathways as a therapeutic approach. ,Sarah J Taylor ... Simon P Langdon [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [3] => Array ( [ArticleId] => 4 [Create_Time] => 2020-02-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202010/20201027055643.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A10024/10024.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A10024/10024.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A10024/10024_cover.png [JournalsId] => 4 [Title] => Colorectal cancer genomic biomarkers in the clinical management of patients with metastatic colorectal carcinoma [Abstract] => Colorectal carcinoma (CRC) is an heterogeneous disease in which different genetic alterations play a role in its pathogenesis and progression and offer potential for therapeutic intervention. The re [AbstractComplete] =>Colorectal carcinoma (CRC) is an heterogeneous disease in which different genetic alterations play a role in its pathogenesis and progression and offer potential for therapeutic intervention. The research on predictive biomarkers in metastatic CRC (mCRC) mainly focused on the identification of biomarkers of response or resistance to anti-epidermal growth factor receptor monoclonal antibodies. In this respect, international guidelines suggest testing mCRC patients only for KRAS, NRAS and BRAF mutations and for microsatellite instability. However, the use of novel testing methods is raising relevant issue related to these biomarkers, such as the presence of sub-clonal RAS mutations or the clinical interpretation of rare no-V600 BRAF variants. In addition, a number of novel biomarkers is emerging from recent studies including amplification of ERBB2, mutations in ERBB2, MAP2K1 and NF1 and rearrangements of ALK, ROS1, NTRK and RET. Mutations in POLE and the levels of tumor mutation burden also appear as possible biomarkers of response to immunotherapy in CRC. Finally, the consensus molecular subtypes classification of CRC based on gene expression profiling has prognostic and predictive implications. Integration of all these information will be likely necessary in the next future in order to improve precision/personalized medicine in mCRC patients.
[Names] => Anna Maria Rachiglio ... Nicola Normanno [Doi] => 10.37349/etat.2020.00004 [Published] => February 29, 2020 [Viewed] => 4719 [Downloaded] => 136 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00004 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:53–70 [Recommend] => 0 [Keywords] => Colorectal carcinoma, molecular biomarker, precision medicine [DetailTitle] => [DetailUrl] => [Id] => 10024 [ris] => https://www.explorationpub.com/uploads/Article/A10024/b3a122a3ec480f579809d86d2c3a9bdf.ris [bib] => https://www.explorationpub.com/uploads/Article/A10024/7a0f4826f5a08f71b91f9c47c0fa7f01.bib [ens] => [Cited] => 5 [Cited_Time] => 2024-04-27 [CitethisArticle] => Rachiglio AM, Sacco A, Forgione L, Esposito C, Chicchinelli N, Normanno N. Colorectal cancer genomic biomarkers in the clinical management of patients with metastatic colorectal carcinoma. Explor Target Antitumor Ther. 2020;1:53-70. https://doi.org/10.37349/etat.2020.00004 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Colorectal cancer genomic biomarkers in the clinical management of patients with metastatic colorectal carcinoma, Colorectal carcinoma, molecular biomarker, precision medicine, Colorectal carcinoma (CRC) is an heterogeneous disease in which different genetic alterations play a role in its pathogenesis and progression and offer potential for therapeutic intervention. The research on predictive biomarkers in metastatic CRC (mCRC) mainly focused on the identification of biomarkers of response or resistance to anti-epidermal growth factor receptor monoclonal antibodies. In this respect, international guidelines suggest testing mCRC patients only for KRAS, NRAS and BRAF mutations and for microsatellite instability. However, the use of novel testing methods is raising relevant issue related to these biomarkers, such as the presence of sub-clonal RAS mutations or the clinical interpretation of rare no-V600 BRAF variants. In addition, a number of novel biomarkers is emerging from recent studies including amplification of ERBB2, mutations in ERBB2, MAP2K1 and NF1 and rearrangements of ALK, ROS1, NTRK and RET. Mutations in POLE and the levels of tumor mutation burden also appear as possible biomarkers of response to immunotherapy in CRC. Finally, the consensus molecular subtypes classification of CRC based on gene expression profiling has prognostic and predictive implications. Integration of all these information will be likely necessary in the next future in order to improve precision/personalized medicine in mCRC patients. ,Anna Maria Rachiglio ... Nicola Normanno [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [4] => Array ( [ArticleId] => 15 [Create_Time] => 2020-04-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202010/20201027070903.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A10026/10026.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A10026/10026.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A10026/10026_cover.png [JournalsId] => 4 [Title] => Implementation of an NGS panel for clinical practice in paraffin-embedded tissue samples from locally advanced and metastatic melanoma patients [Abstract] => Aim: Single biomarker diagnostic test of BRAFV600 locus in metastatic melanoma is mandatory for treatment decision; however, multiple-gene based techniques, such as targeted next-generation sequenc [AbstractComplete] =>Single biomarker diagnostic test of BRAFV600 locus in metastatic melanoma is mandatory for treatment decision; however, multiple-gene based techniques, such as targeted next-generation sequencing (NGS) are being used to maximize the number of patients that can benefit from a targeted therapy. The main objective of this study is to investigate whether an NGS panel could be adopted in routine clinical care for advanced melanoma.
Patients diagnosed with advanced melanoma at our center from 2017 to 2019 were included. Presence of genetic alterations was performed using two methods: real-time polymerase chain reaction-based Idylla test (Biocartis) and NGS with the oncomine solid tumor DNA kit (Thermo Fisher Scientific). Total genomic DNA was extracted from formalin-fixed and paraffin embedded samples for sequencing.
A total of 155 samples were evaluated for molecular analysis but 40 samples (25.8%) were inadequate for sequencing. The clinical utility of BRAFV600 real-time polymerase chain reaction and targeted-NGS was compared in 29 samples and a very good concordance was observed (Kappa = 0.89, 95% confidence interval 0.68 ± 1.05). An oncogenic mutation by NGS was found in 75 samples (65%)–53% of whom were candidates for personalized therapies. The most prevalent mutated genes were BRAF (39%), TP53 (23%), and NRAS (14%). Other genes identified at lower incidence (< 5%) were: PIK3CA, ERBB4, CTNNB1, STK11, FGFR1, SMAD4, KRAS, FGFR3, PTEN and AKT. Co-occurrence of oncogenic mutations was detected in 40% of the samples. Among the mutations identified, TP53 was significantly more prevalent in men (men 31.8% versus women 12.2%, P = 0.03) and NRAS in women (men 9.1% versus women 24.4%, P = 0.03).
Targeted-NGS testing is a feasible technique to implement in the routine clinical practice. Based on our results, NGS has provided more information on target-genes than RT-PCR technique, maximizing the benefit for patients with advanced melanoma.
Dysregulation of cellular pH is frequent in solid tumours and provides potential opportunities for therapeutic intervention. The acidic microenvironment within a tumour can promote migration, invasion and metastasis of cancer cells through a variety of mechanisms. Pathways associated with the control of intracellular pH that are under consideration for intervention include carbonic anhydrase IX, the monocarboxylate transporters (MCT, MCT1 and MCT4), the vacuolar-type H+-ATPase proton pump, and the sodium-hydrogen exchanger 1. This review will describe progress in the development of inhibitors to these targets.
[Names] => Carol Ward ... Simon P Langdon [Doi] => 10.37349/etat.2020.00005 [Published] => April 28, 2020 [Viewed] => 14261 [Downloaded] => 667 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00005 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:71–100 [Recommend] => 0 [Keywords] => Tumour pH, acidosis, inhibitor, hypoxia, carbonic anhydrase IX, sodium-hydrogen exchanger 1, monocarboxylate transporter 1, monocarboxylate transporter 4, vacuolar-type H+-ATPase proton pump [DetailTitle] => [DetailUrl] => [Id] => 10025 [ris] => https://www.explorationpub.com/uploads/Article/A10025/e3db4ebc56942b2dfc401f9e33336235.ris [bib] => https://www.explorationpub.com/uploads/Article/A10025/37ab25104248a033f462d57f9fd7a81e.bib [ens] => [Cited] => 61 [Cited_Time] => 2024-04-27 [CitethisArticle] => Ward C, Meehan J, Gray ME, Murray AF, Argyle DJ, Kunkler IH, et al. The impact of tumour pH on cancer progression: strategies for clinical intervention. Explor Target Antitumor Ther. 2020;1:71-100. https://doi.org/10.37349/etat.2020.00005 [Jindex] => 0 [CName] => Simon PLangdon, [CEmail] => simon.langdon@ed.ac.uk, [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => The impact of tumour pH on cancer progression: strategies for clinical intervention, Tumour pH, acidosis, inhibitor, hypoxia, carbonic anhydrase IX, sodium-hydrogen exchanger 1, monocarboxylate transporter 1, monocarboxylate transporter 4, vacuolar-type H+-ATPase proton pump, Dysregulation of cellular pH is frequent in solid tumours and provides potential opportunities for therapeutic intervention. The acidic microenvironment within a tumour can promote migration, invasion and metastasis of cancer cells through a variety of mechanisms. Pathways associated with the control of intracellular pH that are under consideration for intervention include carbonic anhydrase IX, the monocarboxylate transporters (MCT, MCT1 and MCT4), the vacuolar-type H+-ATPase proton pump, and the sodium-hydrogen exchanger 1. This review will describe progress in the development of inhibitors to these targets. ,Carol Ward ... Simon P Langdon [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [6] => Array ( [ArticleId] => 23 [Create_Time] => 2020-04-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202010/20201029071711.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A10027/10027.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A10027/10027.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A10027/10027_cover.png [JournalsId] => 4 [Title] => Multiple adverse drug reactions during all-trans retinoic acid treatment for acute promyelocytic leukemia: differentiation syndrome, bradycardia, intestinal necrosis [Abstract] => All-trans retinoic acid (ATRA) induces complete remission in a high proportion of acute promyelocytic leukemia (APL). Nevertheless it is be associated with adverse drug reactions that might be life- [AbstractComplete] =>All-trans retinoic acid (ATRA) induces complete remission in a high proportion of acute promyelocytic leukemia (APL). Nevertheless it is be associated with adverse drug reactions that might be life-threatening including differentiation syndrome, myocarditis, myositis, Sweet’s syndrome and ulcers. We describe a case of APL who during induction therapy developed ATRA syndrome, cardiac arrhythmia and multiple episodes of intestinal necrosis that required surgery. In particular, we report here for the first intestinal necrosis attributable to ATRA treatment in the absence of histological evidence of promyelocytes infiltration or leukocytoclastic vasculitis.
[Names] => Valeria Ferla ... Nicola Stefano Fracchiolla [Doi] => 10.37349/etat.2020.00007 [Published] => April 28, 2020 [Viewed] => 2273 [Downloaded] => 23 [Subject] => Case Report [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00007 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:109–116 [Recommend] => 0 [Keywords] => Acute promyelocytic leukemia, all-trans retinoic acid, adverse drug reaction [DetailTitle] => [DetailUrl] => [Id] => 10027 [ris] => https://www.explorationpub.com/uploads/Article/A10027/24f11ec65fb073924b42a600dc492d5a.ris [bib] => https://www.explorationpub.com/uploads/Article/A10027/66dec0fd611ec2054fc09a928e6708c6.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Ferla V, Sciumè M, Gianelli U, Baldini L, Fracchiolla NS. Multiple adverse drug reactions during all-trans retinoic acid treatment for acute promyelocytic leukemia: differentiation syndrome, bradycardia, intestinal necrosis. Explor Target Antitumor Ther. 2020;1:109-16. https://doi.org/10.37349/etat.2020.00007 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Multiple adverse drug reactions during all-trans retinoic acid treatment for acute promyelocytic leukemia: differentiation syndrome, bradycardia, intestinal necrosis, Acute promyelocytic leukemia, all-trans retinoic acid, adverse drug reaction, All-trans retinoic acid (ATRA) induces complete remission in a high proportion of acute promyelocytic leukemia (APL). Nevertheless it is be associated with adverse drug reactions that might be life-threatening including differentiation syndrome, myocarditis, myositis, Sweet’s syndrome and ulcers. We describe a case of APL who during induction therapy developed ATRA syndrome, cardiac arrhythmia and multiple episodes of intestinal necrosis that required surgery. In particular, we report here for the first intestinal necrosis attributable to ATRA treatment in the absence of histological evidence of promyelocytes infiltration or leukocytoclastic vasculitis. ,Valeria Ferla ... Nicola Stefano Fracchiolla [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [7] => Array ( [ArticleId] => 26 [Create_Time] => 2020-04-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202010/20201029084000.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A10028/10028.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A10028/10028.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A10028/10028_cover.png [JournalsId] => 4 [Title] => Angiogenesis and epidermal growth factor receptor inhibitors in non-small cell lung cancer [Abstract] => Several preclinical studies suggested a potential benefit from combined treatment with inhibitors of epidermal growth factor receptor (EGFR) and angiogenesis, both effective in patients with advance [AbstractComplete] =>Several preclinical studies suggested a potential benefit from combined treatment with inhibitors of epidermal growth factor receptor (EGFR) and angiogenesis, both effective in patients with advanced non-small-cell lung cancer (NSCLC). In pretreated patients with advanced EGFR wild type NSCLC, bevacizumab plus erlotinib improved progression-free survival as second-line therapy in the BeTa study and as maintenance therapy in the ATLAS trial, although the benefit was modest and did not translate into an advantage in overall survival. Disappointing results were reported with oral VEGF inhibitors plus erlotinib in pretreated patients with EGFR wild type NSCLC. On the contrary, erlotinib plus bevacizumab or ramucirumab showed a clinically relevant improvement of progression-free survival in naïve patients with EGFR mutations, leading to the approval of these two regimens as first-line treatment of NSCLC patients with EGFR mutant tumors. Several clinical studies are evaluating the feasibility and activity of osimertinib plus bevacizumab or ramucirumab. However, limits that could affect its use in clinical practice are the need of an intravenous infusion for angiogenesis inhibitors, the increased incidence of treatment associated adverse events, the exclusion of patients with tumors located in central position or at risk of hemorrhage. The identification of predictive biomarkers is an important goal of research to optimize the combined use of these agents.
[Names] => Giuliano Palumbo ... Alessandro Morabito [Doi] => 10.37349/etat.2020.00008 [Published] => April 28, 2020 [Viewed] => 2391 [Downloaded] => 60 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00008 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:117–130 [Recommend] => 0 [Keywords] => Lung cancer, angiogenesis, tyrosine kinase inhibitor, erlotinib, bevacizumab [DetailTitle] => [DetailUrl] => [Id] => 10028 [ris] => https://www.explorationpub.com/uploads/Article/A10028/a03d820fd67c55e0e57e1a3933e33bf4.ris [bib] => https://www.explorationpub.com/uploads/Article/A10028/ab166ce4f4f5e30de72c097ff36a8eaa.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Palumbo G, Esposito G, Carillio G, Manzo A, Montanino A, Sforza V, et al. Angiogenesis and epidermal growth factor receptor inhibitors in non-small cell lung cancer. Explor Target Antitumor Ther. 2020;1:117-30. https://doi.org/10.37349/etat.2020.00008 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Angiogenesis and epidermal growth factor receptor inhibitors in non-small cell lung cancer, Lung cancer, angiogenesis, tyrosine kinase inhibitor, erlotinib, bevacizumab, Several preclinical studies suggested a potential benefit from combined treatment with inhibitors of epidermal growth factor receptor (EGFR) and angiogenesis, both effective in patients with advanced non-small-cell lung cancer (NSCLC). In pretreated patients with advanced EGFR wild type NSCLC, bevacizumab plus erlotinib improved progression-free survival as second-line therapy in the BeTa study and as maintenance therapy in the ATLAS trial, although the benefit was modest and did not translate into an advantage in overall survival. Disappointing results were reported with oral VEGF inhibitors plus erlotinib in pretreated patients with EGFR wild type NSCLC. On the contrary, erlotinib plus bevacizumab or ramucirumab showed a clinically relevant improvement of progression-free survival in naïve patients with EGFR mutations, leading to the approval of these two regimens as first-line treatment of NSCLC patients with EGFR mutant tumors. Several clinical studies are evaluating the feasibility and activity of osimertinib plus bevacizumab or ramucirumab. However, limits that could affect its use in clinical practice are the need of an intravenous infusion for angiogenesis inhibitors, the increased incidence of treatment associated adverse events, the exclusion of patients with tumors located in central position or at risk of hemorrhage. The identification of predictive biomarkers is an important goal of research to optimize the combined use of these agents. ,Giuliano Palumbo ... Alessandro Morabito [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [8] => Array ( [ArticleId] => 30 [Create_Time] => 2020-06-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202011/20201119090940.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A10029/10029.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A10029/10029.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A10029/10029_cover.png [JournalsId] => 4 [Title] => Development of PROTACs to address clinical limitations associated with BTK-targeted kinase inhibitors [Abstract] => Chronic lymphocytic leukemia is a common form of leukemia and is dependent on growth-promoting signaling via the B-cell receptor. The Bruton tyrosine kinase (BTK) is an important mediator of B-cell [AbstractComplete] =>Chronic lymphocytic leukemia is a common form of leukemia and is dependent on growth-promoting signaling via the B-cell receptor. The Bruton tyrosine kinase (BTK) is an important mediator of B-cell receptor signaling and the irreversible BTK inhibitor ibrutinib can trigger dramatic clinical responses in treated patients. However, emergence of resistance and toxicity are major limitations which lead to treatment discontinuation. There remains, therefore, a clear need for new therapeutic options. In this review, we discuss recent progress in the development of BTK-targeted proteolysis targeting chimeras (PROTACs) describing how such agents may provide advantages over ibrutinib and highlighting features of PROTACs that are important for the development of effective BTK degrading agents. Overall, PROTACs appear to be an exciting new approach to target BTK. However, development is at a very early stage and considerable progress is required to refine these agents and optimize their drug-like properties before progression to clinical testing.
[Names] => Rachael Arthur ... Graham Packham [Doi] => 10.37349/etat.2020.00009 [Published] => June 29, 2020 [Viewed] => 6993 [Downloaded] => 277 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00009 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 27 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:131–152 [Recommend] => 0 [Keywords] => Chronic lymphocytic leukemia, B-cell receptor, signaling, BTK, ibrutinib, proteolysis targeting chimera [DetailTitle] => Proteolysis Targeting Chimera (PROTAC) [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/27 [Id] => 10029 [ris] => https://www.explorationpub.com/uploads/Article/A10029/3a8177c4fa0e737ba794a369cea12931.ris [bib] => https://www.explorationpub.com/uploads/Article/A10029/a2e3c9edb35bdde53c7ea5c2761965f2.bib [ens] => [Cited] => 14 [Cited_Time] => 2024-04-27 [CitethisArticle] => Arthur R, Valle-Argos B, Steele AJ, Packham G. Development of PROTACs to address clinical limitations associated with BTK-targeted kinase inhibitors. Explor Target Antitumor Ther. 2020;1:131-52. https://doi.org/10.37349/etat.2020.00009 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Development of PROTACs to address clinical limitations associated with BTK-targeted kinase inhibitors, Chronic lymphocytic leukemia, B-cell receptor, signaling, BTK, ibrutinib, proteolysis targeting chimera, Chronic lymphocytic leukemia is a common form of leukemia and is dependent on growth-promoting signaling via the B-cell receptor. The Bruton tyrosine kinase (BTK) is an important mediator of B-cell receptor signaling and the irreversible BTK inhibitor ibrutinib can trigger dramatic clinical responses in treated patients. However, emergence of resistance and toxicity are major limitations which lead to treatment discontinuation. There remains, therefore, a clear need for new therapeutic options. In this review, we discuss recent progress in the development of BTK-targeted proteolysis targeting chimeras (PROTACs) describing how such agents may provide advantages over ibrutinib and highlighting features of PROTACs that are important for the development of effective BTK degrading agents. Overall, PROTACs appear to be an exciting new approach to target BTK. However, development is at a very early stage and considerable progress is required to refine these agents and optimize their drug-like properties before progression to clinical testing. ,Rachael Arthur ... Graham Packham [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [9] => Array ( [ArticleId] => 34 [Create_Time] => 2020-06-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202011/20201119091528.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100210/100210.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100210/100210.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100210/100210_cover.png [JournalsId] => 4 [Title] => An overview of the anti-cancer actions of Tanshinones, derived from Salvia miltiorrhiza (Danshen) [Abstract] => Tanshinone is a herbal medicinal compound described in Chinese medicine, extracted from the roots of Salvia miltiorrhiza (Danshen). This family of compounds, including Tanshinone IIA and Tanshinone [AbstractComplete] =>Tanshinone is a herbal medicinal compound described in Chinese medicine, extracted from the roots of Salvia miltiorrhiza (Danshen). This family of compounds, including Tanshinone IIA and Tanshinone I, have shown remarkable potential as anti-cancer molecules, especially against breast, cervical, colorectal, gastric, lung, and prostate cancer cell lines, as well as leukaemia, melanoma, and hepatocellular carcinoma among others. Recent data has indicated that Tanshinones can modulate multiple molecular pathways such as PI3K/Akt, MAPK and JAK/STAT3, and exert their pharmacological effects against different malignancies. In addition, preclinical and clinical data, together with the safety profile of Tanshinones, encourage further applications of these compounds in cancer therapeutics. In this review article, the effect of Tanshinones on different cancers, challenges in their pharmacological development, and opportunities to harness their clinical potential have been documented.
[Names] => Irum Naz ... Kwang Seok Ahn [Doi] => 10.37349/etat.2020.00010 [Published] => June 29, 2020 [Viewed] => 3957 [Downloaded] => 87 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00010 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 31 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:153–170 [Recommend] => 0 [Keywords] => Tanshinone, cancer, signalling pathways, apoptosis, angiogenesis, pharmacokinetics [DetailTitle] => Targeting Transcription Factors for Cancer Therapy [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/31 [Id] => 100210 [ris] => https://www.explorationpub.com/uploads/Article/A100210/0611f0d45821ef5be43049b99c98ceb3.ris [bib] => https://www.explorationpub.com/uploads/Article/A100210/3be412f4c3abd7cdf19354ee0530153d.bib [ens] => [Cited] => 9 [Cited_Time] => 2024-04-27 [CitethisArticle] => Naz I, Merarchi M, Ramchandani S, Khan MR, Malik MN, Sarwar S, et al. An overview of the anti-cancer actions of Tanshinones, derived from Salvia miltiorrhiza (Danshen). Explor Target Antitumor Ther. 2020;1:153-70. https://doi.org/10.37349/etat.2020.00010 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => An overview of the anti-cancer actions of Tanshinones, derived from Salvia miltiorrhiza (Danshen), Tanshinone, cancer, signalling pathways, apoptosis, angiogenesis, pharmacokinetics, Tanshinone is a herbal medicinal compound described in Chinese medicine, extracted from the roots of Salvia miltiorrhiza (Danshen). This family of compounds, including Tanshinone IIA and Tanshinone I, have shown remarkable potential as anti-cancer molecules, especially against breast, cervical, colorectal, gastric, lung, and prostate cancer cell lines, as well as leukaemia, melanoma, and hepatocellular carcinoma among others. Recent data has indicated that Tanshinones can modulate multiple molecular pathways such as PI3K/Akt, MAPK and JAK/STAT3, and exert their pharmacological effects against different malignancies. In addition, preclinical and clinical data, together with the safety profile of Tanshinones, encourage further applications of these compounds in cancer therapeutics. In this review article, the effect of Tanshinones on different cancers, challenges in their pharmacological development, and opportunities to harness their clinical potential have been documented. ,Irum Naz ... Kwang Seok Ahn [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [10] => Array ( [ArticleId] => 36 [Create_Time] => 2020-06-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202011/20201119093541.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100212/100212.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100212/100212.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100212/100212_cover.png [JournalsId] => 4 [Title] => Role of liquid biopsy for thoracic cancers immunotherapy [Abstract] => Immunotherapy has shifted the therapeutic landscape in thoracic cancers. However, assessment of biomarkers for patient selection and disease monitoring remain challenging, especially considering the [AbstractComplete] =>Immunotherapy has shifted the therapeutic landscape in thoracic cancers. However, assessment of biomarkers for patient selection and disease monitoring remain challenging, especially considering the lack of tissue sample availability for clinical and research purposes. In this scenario, liquid biopsy (LB), defined as the study and characterization of biomarkers in body fluids, represents a useful alternative strategy. In other malignancies such as colorectal cancer, breast cancer or melanoma, the potential of LB has been more extensively explored for monitoring minimal residual disease or response to treatment, and to investigate mechanisms of resistance to targeted agents. Even if various experiences have already been published about the applications of LB in immunotherapy in thoracic cancers, the standardization of methodology and assessment of its clinical utility is still pending. In this review, the authors will focus on the applications of LB in immunotherapy in non-small cell lung cancer, small cell lung cancer, and malignant pleural mesothelioma, describing available data and future perspectives.
[Names] => Raimondo Di Liello ... Paloma Martín-Martorell [Doi] => 10.37349/etat.2020.00012 [Published] => June 29, 2020 [Viewed] => 3308 [Downloaded] => 59 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00012 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 23 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:183–199 [Recommend] => 0 [Keywords] => Liquid biopsy, thoracic cancer, non-small cell lung cancer, small cell lung cancer, mesothelioma, circulating tumor cells, tumor mutational burden, programmed cell death ligand 1 [DetailTitle] => Liquid Biopsy in Thoracic Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/23 [Id] => 100212 [ris] => https://www.explorationpub.com/uploads/Article/A100212/d7e26b8396a35684140e08219dc2dc07.ris [bib] => https://www.explorationpub.com/uploads/Article/A100212/cbdb175de0bdeffe0b4f72bdd9730e87.bib [ens] => [Cited] => 5 [Cited_Time] => 2024-04-26 [CitethisArticle] => Di Liello R, Cimmino F, Simón S, Giunta EF, De Falco V, Martín-Martorell P. Role of liquid biopsy for thoracic cancers immunotherapy. Explor Target Antitumor Ther. 2020;1:183-99. https://doi.org/10.37349/etat.2020.00012 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Role of liquid biopsy for thoracic cancers immunotherapy, Liquid biopsy, thoracic cancer, non-small cell lung cancer, small cell lung cancer, mesothelioma, circulating tumor cells, tumor mutational burden, programmed cell death ligand 1, Immunotherapy has shifted the therapeutic landscape in thoracic cancers. However, assessment of biomarkers for patient selection and disease monitoring remain challenging, especially considering the lack of tissue sample availability for clinical and research purposes. In this scenario, liquid biopsy (LB), defined as the study and characterization of biomarkers in body fluids, represents a useful alternative strategy. In other malignancies such as colorectal cancer, breast cancer or melanoma, the potential of LB has been more extensively explored for monitoring minimal residual disease or response to treatment, and to investigate mechanisms of resistance to targeted agents. Even if various experiences have already been published about the applications of LB in immunotherapy in thoracic cancers, the standardization of methodology and assessment of its clinical utility is still pending. In this review, the authors will focus on the applications of LB in immunotherapy in non-small cell lung cancer, small cell lung cancer, and malignant pleural mesothelioma, describing available data and future perspectives. ,Raimondo Di Liello ... Paloma Martín-Martorell [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [11] => Array ( [ArticleId] => 37 [Create_Time] => 2020-06-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202207/20220720102535.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100211/100211.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100211/100211.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100211/100211_cover.png [JournalsId] => 4 [Title] => Integration of PARP-inhibitors in ovarian cancer therapy [Abstract] => Poly-ADP-ribose polymerase inhibitors (PARP-I) represent one of the most attractive and promising class of biological agents studied both in relapsed ovarian cancer (OC) and in the advanced setting. [AbstractComplete] =>Poly-ADP-ribose polymerase inhibitors (PARP-I) represent one of the most attractive and promising class of biological agents studied both in relapsed ovarian cancer (OC) and in the advanced setting. The availability of this new class of drugs has changed the clinical management of OC ensuring an unprecedented advance in such an aggressive cancer. Three oral PARP-I are currently available: olaparib, niraparib and rucaparib. Another two are in active clinical exploration: veliparib and talazoparib. Here the authors report clinical data with PARP-I with a particular emphasis on the phase II and III trials that support PARP-I approval by regulatory agencies in OC patients.
[Names] => Antonella Pietragalla ... Gennaro Daniele [Doi] => 10.37349/etat.2020.00011 [Published] => June 29, 2020 [Viewed] => 2201 [Downloaded] => 37 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00011 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:171–182 [Recommend] => 0 [Keywords] => PARP-inhibitors, ovarian cancer, BRCA1 and 2, homologous recombination deficiency, DNA repair [DetailTitle] => [DetailUrl] => [Id] => 100211 [ris] => https://www.explorationpub.com/uploads/Article/A100211/d6ffa71522fdd8872d928357b4cd02a7.ris [bib] => https://www.explorationpub.com/uploads/Article/A100211/73e3b69e4715769bde893cb18423aa86.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-26 [CitethisArticle] => Pietragalla A, Ciccarone F, Nero C, Scambia G, Lorusso D, Daniele G. Integration of PARP-inhibitors in ovarian cancer therapy. Explor Target Antitumor Ther. 2020;1:171-82. https://doi.org/10.37349/etat.2020.00011 [Jindex] => 0 [CName] => GennaroDaniele, [CEmail] => gennaro.daniele@policlinicogemelli.it, [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Integration of PARP-inhibitors in ovarian cancer therapy, PARP-inhibitors, ovarian cancer, BRCA1 and 2, homologous recombination deficiency, DNA repair, Poly-ADP-ribose polymerase inhibitors (PARP-I) represent one of the most attractive and promising class of biological agents studied both in relapsed ovarian cancer (OC) and in the advanced setting. The availability of this new class of drugs has changed the clinical management of OC ensuring an unprecedented advance in such an aggressive cancer. Three oral PARP-I are currently available: olaparib, niraparib and rucaparib. Another two are in active clinical exploration: veliparib and talazoparib. Here the authors report clinical data with PARP-I with a particular emphasis on the phase II and III trials that support PARP-I approval by regulatory agencies in OC patients. ,Antonella Pietragalla ... Gennaro Daniele [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [12] => Array ( [ArticleId] => 57 [Create_Time] => 2020-07-22 [zipUrl] => https://www.explorationpub.com/uploads/zip/202011/20201119094405.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100213/100213.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100213/100213.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100213/100213-cover.png [JournalsId] => 4 [Title] => A brief overview of antitumoral actions of bruceine D [Abstract] => Cancer remains the second leading cause of mortality globally. In combating cancer, conventional chemotherapy and/or radiotherapy are administered as first-line therapy. However, these are usually a [AbstractComplete] =>Cancer remains the second leading cause of mortality globally. In combating cancer, conventional chemotherapy and/or radiotherapy are administered as first-line therapy. However, these are usually accompanied with adverse side effects that decrease the quality of patient’s lives. As such, natural bioactive compounds have gained an attraction in the scientific and medical community as evidence of their anticancer properties and attenuation of side effects mounted. In particular, quassinoids have been found to exhibit a plethora of inhibitory activities such as anti-proliferative effects on tumor development and metastasis. Recently, bruceine D, a quassinoid isolated from the shrub Brucea javanica (L.) Merr. (Simaroubaceae), has come under immense investigation on its antineoplastic properties in various human cancers including pancreas, breast, lung, blood, bone, and liver. In this review, we have highlighted the antineoplastic effects of bruceine D and its mode of actions in different tumor models.
[Names] => Zi Wayne Sin ... Manoj Garg [Doi] => 10.37349/etat.2020.00013 [Published] => August 31, 2020 [Viewed] => 2973 [Downloaded] => 62 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00013 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 31 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:200–217 [Recommend] => 0 [Keywords] => Cancer, bruceine D, epithelial-to-mesenchymal transition, cancer stem cells, metastasis, apoptosis, anti-inflammatory, PI3K/AKT/ERK pathway [DetailTitle] => Targeting Transcription Factors for Cancer Therapy [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/31 [Id] => 100213 [ris] => https://www.explorationpub.com/uploads/Article/A100213/2417aaf815feda1d01d8dafbedac82de.ris [bib] => https://www.explorationpub.com/uploads/Article/A100213/17c9a9a5181ce7148ff2d53639ca0ab6.bib [ens] => [Cited] => 7 [Cited_Time] => 2024-04-27 [CitethisArticle] => Sin ZW, Bhardwaj V, Pandey AK, Garg M. A brief overview of antitumoral actions of bruceine D. Explor Target Antitumor Ther. 2020;1:200-17. https://doi.org/10.37349/etat.2020.00013 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => A brief overview of antitumoral actions of bruceine D, Cancer, bruceine D, epithelial-to-mesenchymal transition, cancer stem cells, metastasis, apoptosis, anti-inflammatory, PI3K/AKT/ERK pathway, Cancer remains the second leading cause of mortality globally. In combating cancer, conventional chemotherapy and/or radiotherapy are administered as first-line therapy. However, these are usually accompanied with adverse side effects that decrease the quality of patient’s lives. As such, natural bioactive compounds have gained an attraction in the scientific and medical community as evidence of their anticancer properties and attenuation of side effects mounted. In particular, quassinoids have been found to exhibit a plethora of inhibitory activities such as anti-proliferative effects on tumor development and metastasis. Recently, bruceine D, a quassinoid isolated from the shrub Brucea javanica (L.) Merr. (Simaroubaceae), has come under immense investigation on its antineoplastic properties in various human cancers including pancreas, breast, lung, blood, bone, and liver. In this review, we have highlighted the antineoplastic effects of bruceine D and its mode of actions in different tumor models. ,Zi Wayne Sin ... Manoj Garg [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [13] => Array ( [ArticleId] => 60 [Create_Time] => 2020-08-14 [zipUrl] => https://www.explorationpub.com/uploads/zip/202011/20201119100809.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100215/100215.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100215/100215.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100215/100215-cover.png [JournalsId] => 4 [Title] => Future directions and management of liquid biopsy in non-small cell lung cancer [Abstract] => Lung cancer represents the world’s most common cause of cancer death. In recent years, we moved from a generic therapeutic strategy to a personalized approach, based on the molecular char [AbstractComplete] =>Lung cancer represents the world’s most common cause of cancer death. In recent years, we moved from a generic therapeutic strategy to a personalized approach, based on the molecular characterization of the tumor. In this view, liquid biopsy is becoming an important tool for assessing the progress or onset of lung disease. Liquid biopsy is a non-invasive procedure able to isolate circulating tumor cells, tumor educated platelets, exosomes and free circulating tumor DNA from body fluids. The characterization of these liquid biomarkers can help to choose the therapeutic strategy for each different case. In this review, the authors will analyze the main aspects of lung cancer and the applications currently in use focusing on the benefits associated with this approach for predicting the prognosis and monitoring the clinical conditions of lung cancer disease.
[Names] => Alessia Maria Cossu ... Marco Bocchetti [Doi] => 10.37349/etat.2020.00015 [Published] => August 31, 2020 [Viewed] => 2762 [Downloaded] => 59 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00015 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 23 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:239–252 [Recommend] => 0 [Keywords] => Non-small cell lung cancer, biomarkers, liquid biopsy, circulating cell-free tumor DNA, molecular analysis [DetailTitle] => Liquid Biopsy in Thoracic Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/23 [Id] => 100215 [ris] => https://www.explorationpub.com/uploads/Article/A100215/4b6f6c6ee0b07cf6f94650373fcbb5ba.ris [bib] => https://www.explorationpub.com/uploads/Article/A100215/3f9574e11867957b28e2270e3a512e7e.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-27 [CitethisArticle] => Cossu AM, Scrima M, Lombardi A, Grimaldi A, Russo M, Ottaiano A, et al. Future directions and management of liquid biopsy in non-small cell lung cancer. Explor Target Antitumor Ther. 2020;1:239-52. https://doi.org/10.37349/etat.2020.00015 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Future directions and management of liquid biopsy in non-small cell lung cancer, Non-small cell lung cancer, biomarkers, liquid biopsy, circulating cell-free tumor DNA, molecular analysis, Lung cancer represents the world’s most common cause of cancer death. In recent years, we moved from a generic therapeutic strategy to a personalized approach, based on the molecular characterization of the tumor. In this view, liquid biopsy is becoming an important tool for assessing the progress or onset of lung disease. Liquid biopsy is a non-invasive procedure able to isolate circulating tumor cells, tumor educated platelets, exosomes and free circulating tumor DNA from body fluids. The characterization of these liquid biomarkers can help to choose the therapeutic strategy for each different case. In this review, the authors will analyze the main aspects of lung cancer and the applications currently in use focusing on the benefits associated with this approach for predicting the prognosis and monitoring the clinical conditions of lung cancer disease. ,Alessia Maria Cossu ... Marco Bocchetti [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [14] => Array ( [ArticleId] => 61 [Create_Time] => 2020-08-14 [zipUrl] => https://www.explorationpub.com/uploads/zip/202009/20200925023549.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100216/100216.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100216/100216.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100216/100216-cover.png [JournalsId] => 4 [Title] => Circulating cancer stem cells: an interesting niche to explore [Abstract] => [AbstractComplete] => [Names] => Federica Papaccio [Doi] => 10.37349/etat.2020.00016 [Published] => August 31, 2020 [Viewed] => 2529 [Downloaded] => 81 [Subject] => Commentary [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00016 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 23 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:253–258 [Recommend] => 0 [Keywords] => [DetailTitle] => Liquid Biopsy in Thoracic Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/23 [Id] => 100216 [ris] => https://www.explorationpub.com/uploads/Article/A100216/19cb0e5c0c884aea31451eb5f4777ac1.ris [bib] => https://www.explorationpub.com/uploads/Article/A100216/dbb2aa62cdbe3b560a71961b95165854.bib [ens] => [Cited] => 5 [Cited_Time] => 2024-04-27 [CitethisArticle] => Papaccio F. Circulating cancer stem cells: an interesting niche to explore. Explor Target Antitumor Ther. 2020;1:253-8. https://doi.org/10.37349/etat.2020.00016 [Jindex] => 1 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Circulating cancer stem cells: an interesting niche to explore,,,Federica Papaccio [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [15] => Array ( [ArticleId] => 62 [Create_Time] => 2020-08-18 [zipUrl] => https://www.explorationpub.com/uploads/zip/202011/20201119103127.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100217/100217.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100217/100217.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100217/100217_cover.png [JournalsId] => 4 [Title] => PROTACs are effective in addressing the platelet toxicity associated with BCL-XL inhibitors [Abstract] => BCL-XL is an anti-apoptotic protein that plays an important role in tumorigenesis, metastasis, and intrinsic or therapy-induced cancer drug resistance. More recently, BCL-XL has also been identified [AbstractComplete] =>BCL-XL is an anti-apoptotic protein that plays an important role in tumorigenesis, metastasis, and intrinsic or therapy-induced cancer drug resistance. More recently, BCL-XL has also been identified as a key survival factor in senescent cells. Accumulation of senescent cells has been indicated as a causal factor of aging and many age-related diseases and contributes to tumor relapse and metastasis. Thus, inhibition of BCL-XL is an attractive strategy for the treatment of cancer and extension of healthspan. However, development of BCL-XL inhibitors such as navitoclax for clinical use has been challenging because human platelets depend on BCL-XL for survival. In this review, the authors discuss how BCL-XL-targeted proteolysis targeting chimeras (PROTACs) afford a novel approach to mitigate the on-target thrombocytopenia associated with BCL-XL inhibition. The authors summarize the progress in the development of BCL-XL PROTACs. The authors highlight the in vitro and in vivo data supporting that by hijacking the ubiquitin protein ligase (E3) that are poorly expressed in human platelets, BCL-XL PROTACs can significantly improve the therapeutic window compared to conventional BCL-XL inhibitors. These findings demonstrated the potentially broad utility of PROTAC technology to achieve tissue selectivity through recruiting differentially expressed E3 ligases and to reduce on-target toxicity.
[Names] => Peiyi Zhang ... Guangrong Zheng [Doi] => 10.37349/etat.2020.00017 [Published] => August 31, 2020 [Viewed] => 5473 [Downloaded] => 282 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00017 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 27 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:259–272 [Recommend] => 0 [Keywords] => Apoptosis, BCL-XL, navitoclax, proteolysis targeting chimera, thrombocytopenia [DetailTitle] => Proteolysis Targeting Chimera (PROTAC) [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/27 [Id] => 100217 [ris] => https://www.explorationpub.com/uploads/Article/A100217/3a2003edc6bab3c5b84cedcf1dbeb969.ris [bib] => https://www.explorationpub.com/uploads/Article/A100217/1d6d33cb3b094725d7b3ab572a404274.bib [ens] => [Cited] => 14 [Cited_Time] => 2024-04-27 [CitethisArticle] => Zhang P, Zhang X, Liu X, Khan S, Zhou D, Zheng G. PROTACs are effective in addressing the platelet toxicity associated with BCL-X L inhibitors. Explor Target Antitumor Ther. 2020;1:259-72. https://doi.org/10.37349/etat.2020.00017 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => PROTACs are effective in addressing the platelet toxicity associated with BCL-XL inhibitors, Apoptosis, BCL-XL, navitoclax, proteolysis targeting chimera, thrombocytopenia, BCL-XL is an anti-apoptotic protein that plays an important role in tumorigenesis, metastasis, and intrinsic or therapy-induced cancer drug resistance. More recently, BCL-XL has also been identified as a key survival factor in senescent cells. Accumulation of senescent cells has been indicated as a causal factor of aging and many age-related diseases and contributes to tumor relapse and metastasis. Thus, inhibition of BCL-XL is an attractive strategy for the treatment of cancer and extension of healthspan. However, development of BCL-XL inhibitors such as navitoclax for clinical use has been challenging because human platelets depend on BCL-XL for survival. In this review, the authors discuss how BCL-XL-targeted proteolysis targeting chimeras (PROTACs) afford a novel approach to mitigate the on-target thrombocytopenia associated with BCL-XL inhibition. The authors summarize the progress in the development of BCL-XL PROTACs. The authors highlight the in vitro and in vivo data supporting that by hijacking the ubiquitin protein ligase (E3) that are poorly expressed in human platelets, BCL-XL PROTACs can significantly improve the therapeutic window compared to conventional BCL-XL inhibitors. These findings demonstrated the potentially broad utility of PROTAC technology to achieve tissue selectivity through recruiting differentially expressed E3 ligases and to reduce on-target toxicity. ,Peiyi Zhang ... Guangrong Zheng [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [16] => Array ( [ArticleId] => 65 [Create_Time] => 2020-08-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202011/20201119095555.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100214/100214.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100214/100214.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100214/100214-cover.png [JournalsId] => 4 [Title] => Possible applications of salvianolic acid B against different cancers [Abstract] => Cancer is the second death causing disease worldwide after cardiovascular abnormalities. The difficulty in treating tumor cells with more precise targeted interventions and recurrence of cancer afte [AbstractComplete] =>Cancer is the second death causing disease worldwide after cardiovascular abnormalities. The difficulty in treating tumor cells with more precise targeted interventions and recurrence of cancer after treatment may pose great difficulty in developing sustainable therapeutic regimens. These limitations have prompted the need to explore several compounds with ability to cease tumor growth while at the same time induce apoptosis of tumor cells. Several studies have emphasized the use of natural compounds as antitumor agents due to their high efficacy against cancer cells and low toxicity in normal cells. Salvianolic acid B (SAB), a naturally occurring phenolic compound extracted from the radix of Chinese herb Salvia miltiorrhiza can induce apoptosis in different types of tumor cells. It can be used to treat cardiovascular and neurodegenerative disorders, hepatic fibrosis, and cancers. Several studies have shown that SAB can mitigate tumorigenesis by modulating MAPK, PI3K/AKT, and NF-ĸB signaling pathways. It also sensitizes the tumor cells to different anti-cancer agents by reversing the multi-drug resistance mechanisms found in tumor cells. This review summarizes the studies showing antitumor potential of SAB in different types of cancer cell lines, animal models and highlights the possible mechanisms through which SAB can induce apoptosis, inhibit growth and metastasis in tumor cells. Moreover, the possible role of nano-technological approaches to induce targeted delivery of SAB to eradicate tumor cells has been also discussed.
[Names] => Iram Shahzadi ... Reza Mohammadinejad [Doi] => 10.37349/etat.2020.00014 [Published] => August 31, 2020 [Viewed] => 2894 [Downloaded] => 38 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00014 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 31 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:218–238 [Recommend] => 0 [Keywords] => Salvianolic acid B, polyphenols, apoptosis, molecular targets, cancer [DetailTitle] => Targeting Transcription Factors for Cancer Therapy [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/31 [Id] => 100214 [ris] => https://www.explorationpub.com/uploads/Article/A100214/22dc9d75038fc370406dbffada7d5038.ris [bib] => https://www.explorationpub.com/uploads/Article/A100214/fc59c56de6295f41f91a0ff937029771.bib [ens] => [Cited] => 6 [Cited_Time] => 2024-04-26 [CitethisArticle] => Shahzadi I, Ali Z, Bukhari S, Narula AS, Mirza B, Mohammadinejad R. Possible applications of salvianolic acid B against different cancers. Explor Target Antitumor Ther. 2020;1:218-38. https://doi.org/10.37349/etat.2020.00014 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Possible applications of salvianolic acid B against different cancers, Salvianolic acid B, polyphenols, apoptosis, molecular targets, cancer, Cancer is the second death causing disease worldwide after cardiovascular abnormalities. The difficulty in treating tumor cells with more precise targeted interventions and recurrence of cancer after treatment may pose great difficulty in developing sustainable therapeutic regimens. These limitations have prompted the need to explore several compounds with ability to cease tumor growth while at the same time induce apoptosis of tumor cells. Several studies have emphasized the use of natural compounds as antitumor agents due to their high efficacy against cancer cells and low toxicity in normal cells. Salvianolic acid B (SAB), a naturally occurring phenolic compound extracted from the radix of Chinese herb Salvia miltiorrhiza can induce apoptosis in different types of tumor cells. It can be used to treat cardiovascular and neurodegenerative disorders, hepatic fibrosis, and cancers. Several studies have shown that SAB can mitigate tumorigenesis by modulating MAPK, PI3K/AKT, and NF-ĸB signaling pathways. It also sensitizes the tumor cells to different anti-cancer agents by reversing the multi-drug resistance mechanisms found in tumor cells. This review summarizes the studies showing antitumor potential of SAB in different types of cancer cell lines, animal models and highlights the possible mechanisms through which SAB can induce apoptosis, inhibit growth and metastasis in tumor cells. Moreover, the possible role of nano-technological approaches to induce targeted delivery of SAB to eradicate tumor cells has been also discussed. ,Iram Shahzadi ... Reza Mohammadinejad [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [17] => Array ( [ArticleId] => 69 [Create_Time] => 2020-10-09 [zipUrl] => https://www.explorationpub.com/uploads/zip/202010/20201030110534.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100220/100220.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100220/100220.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100220/100220-cover.png [JournalsId] => 4 [Title] => Diagnostic and prognostic role of liquid biopsy in non-small cell lung cancer: evaluation of circulating biomarkers [Abstract] => Lung cancer is still one of the main causes of cancer-related death, together with prostate and colorectal cancers in males and breast and colorectal cancers in females. The prognosis for non-small [AbstractComplete] =>Lung cancer is still one of the main causes of cancer-related death, together with prostate and colorectal cancers in males and breast and colorectal cancers in females. The prognosis for non-small cell lung cancer (NSCLC) is strictly dependent on feasibility of a complete surgical resection of the tumor at diagnosis. Since surgery is indicated only in early stages tumors, it is necessary to anticipate the timing of diagnosis in clinical practice. In the diagnostic and therapeutic pathway for NSCLC, sampling of neoplastic tissue is usually obtained using invasive methods that are not free from disadvantages and complications. A valid alternative to the standard biopsy is the liquid biopsy (LB), that is, the analysis of samples from peripheral blood, urine, and other biological fluids, with a simple and non-invasive collection. In particular, it is possible to detect in the blood different tumor derivatives, such as cell-free DNA (cfDNA) with its subtype circulating tumor DNA (ctDNA), cell-free RNA (cfRNA), and circulating tumor cells (CTCs). Plasma-based testing seems to have several advantages over tumor tissue biopsy; firstly, it reduces medical costs, risk of complications related to invasive procedures, and turnaround times; moreover, the analysis of genes alteration, such as EGFR, ALK, ROS1, and BRAF is faster and safer with this method, compared to tissue biopsy. Despite all these advantages, the evidences in literatures indicate that assays performed on liquid biopsies have a low sensitivity, making them unsuitable for screening in lung cancer at the current state. This is caused by lack of standardization in sampling and preparation of specimen and by the low concentration of biomarkers in the bloodstream. Instead, routinely use of LB should be preferred in revaluation of patients with advanced NSCLC resistant to chemotherapy, due to onset of new mutations.
[Names] => Giovanni Vicidomini ... Mario Santini [Doi] => 10.37349/etat.2020.00020 [Published] => October 30, 2020 [Viewed] => 2131 [Downloaded] => 33 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00020 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 23 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:343–354 [Recommend] => 0 [Keywords] => Liquid biopsy, lung cancer, circulating tumor cells, circulating tumor DNA, exosomes [DetailTitle] => Liquid Biopsy in Thoracic Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/23 [Id] => 100220 [ris] => https://www.explorationpub.com/uploads/Article/A100220/6b900a83395ca7004446fdd1f87afc09.ris [bib] => https://www.explorationpub.com/uploads/Article/A100220/2a25aa02ea7c7b3293479fd7587766ea.bib [ens] => [Cited] => 4 [Cited_Time] => 2024-04-26 [CitethisArticle] => Vicidomini G, Cascone R, Carlucci A, Fiorelli A, Di Denico M, Santini M. Diagnostic and prognostic role of liquid biopsy in non-small cell lung cancer: evaluation of circulating biomarkers. Explor Target Antitumor Ther. 2020;1:343-54. https://doi.org/10.37349/etat.2020.00020 [Jindex] => 1 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Diagnostic and prognostic role of liquid biopsy in non-small cell lung cancer: evaluation of circulating biomarkers, Liquid biopsy, lung cancer, circulating tumor cells, circulating tumor DNA, exosomes, Lung cancer is still one of the main causes of cancer-related death, together with prostate and colorectal cancers in males and breast and colorectal cancers in females. The prognosis for non-small cell lung cancer (NSCLC) is strictly dependent on feasibility of a complete surgical resection of the tumor at diagnosis. Since surgery is indicated only in early stages tumors, it is necessary to anticipate the timing of diagnosis in clinical practice. In the diagnostic and therapeutic pathway for NSCLC, sampling of neoplastic tissue is usually obtained using invasive methods that are not free from disadvantages and complications. A valid alternative to the standard biopsy is the liquid biopsy (LB), that is, the analysis of samples from peripheral blood, urine, and other biological fluids, with a simple and non-invasive collection. In particular, it is possible to detect in the blood different tumor derivatives, such as cell-free DNA (cfDNA) with its subtype circulating tumor DNA (ctDNA), cell-free RNA (cfRNA), and circulating tumor cells (CTCs). Plasma-based testing seems to have several advantages over tumor tissue biopsy; firstly, it reduces medical costs, risk of complications related to invasive procedures, and turnaround times; moreover, the analysis of genes alteration, such as EGFR, ALK, ROS1, and BRAF is faster and safer with this method, compared to tissue biopsy. Despite all these advantages, the evidences in literatures indicate that assays performed on liquid biopsies have a low sensitivity, making them unsuitable for screening in lung cancer at the current state. This is caused by lack of standardization in sampling and preparation of specimen and by the low concentration of biomarkers in the bloodstream. Instead, routinely use of LB should be preferred in revaluation of patients with advanced NSCLC resistant to chemotherapy, due to onset of new mutations. ,Giovanni Vicidomini ... Mario Santini [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [18] => Array ( [ArticleId] => 70 [Create_Time] => 2020-10-12 [zipUrl] => https://www.explorationpub.com/uploads/zip/202010/20201030105054.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100218/100218.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100218/100218.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100218/100218_cover.png [JournalsId] => 4 [Title] => Current strategies for the design of PROTAC linkers: a critical review [Abstract] => PROteolysis TArgeting Chimeras (PROTACs) are heterobifunctional molecules consisting of two ligands; an “anchor” to bind to an E3 ubiquitin ligase and a “warhead” [AbstractComplete] =>PROteolysis TArgeting Chimeras (PROTACs) are heterobifunctional molecules consisting of two ligands; an “anchor” to bind to an E3 ubiquitin ligase and a “warhead” to bind to a protein of interest, connected by a chemical linker. Targeted protein degradation by PROTACs has emerged as a new modality for the knock down of a range of proteins, with the first agents now reaching clinical evaluation. It has become increasingly clear that the length and composition of the linker play critical roles on the physicochemical properties and bioactivity of PROTACs. While linker design has historically received limited attention, the PROTAC field is evolving rapidly and currently undergoing an important shift from synthetically tractable alkyl and polyethylene glycol to more sophisticated functional linkers. This promises to unlock a wealth of novel PROTAC agents with enhanced bioactivity for therapeutic intervention. Here, the authors provide a timely overview of the diverse linker classes in the published literature, along with their underlying design principles and overall influence on the properties and bioactivity of the associated PROTACs. Finally, the authors provide a critical analysis of current strategies for PROTAC assembly. The authors highlight important limitations associated with the traditional “trial and error” approach around linker design and selection, and suggest potential future avenues to further inform rational linker design and accelerate the identification of optimised PROTACs. In particular, the authors believe that advances in computational and structural methods will play an essential role to gain a better understanding of the structure and dynamics of PROTAC ternary complexes, and will be essential to address the current gaps in knowledge associated with PROTAC design.
[Names] => Robert I. Troup ... Matthias G. J. Baud [Doi] => 10.37349/etat.2020.00018 [Published] => October 30, 2020 [Viewed] => 23217 [Downloaded] => 2918 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00018 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 27 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:273–312 [Recommend] => 0 [Keywords] => PROTAC, protein degradation, linker design [DetailTitle] => Proteolysis Targeting Chimera (PROTAC) [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/27 [Id] => 100218 [ris] => https://www.explorationpub.com/uploads/Article/A100218/e790b256cea0a68f272fff257dbe4129.ris [bib] => https://www.explorationpub.com/uploads/Article/A100218/b5e11d211abd653e8c840f5829fa7aec.bib [ens] => [Cited] => 137 [Cited_Time] => 2024-04-27 [CitethisArticle] => Troup RI, Fallan C, Baud MGJ. Current strategies for the design of PROTAC linkers: a critical review. Explor Target Antitumor Ther. 2020;1:273-312. https://doi.org/10.37349/etat.2020.00018 [Jindex] => 1 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Current strategies for the design of PROTAC linkers: a critical review, PROTAC, protein degradation, linker design, PROteolysis TArgeting Chimeras (PROTACs) are heterobifunctional molecules consisting of two ligands; an “anchor” to bind to an E3 ubiquitin ligase and a “warhead” to bind to a protein of interest, connected by a chemical linker. Targeted protein degradation by PROTACs has emerged as a new modality for the knock down of a range of proteins, with the first agents now reaching clinical evaluation. It has become increasingly clear that the length and composition of the linker play critical roles on the physicochemical properties and bioactivity of PROTACs. While linker design has historically received limited attention, the PROTAC field is evolving rapidly and currently undergoing an important shift from synthetically tractable alkyl and polyethylene glycol to more sophisticated functional linkers. This promises to unlock a wealth of novel PROTAC agents with enhanced bioactivity for therapeutic intervention. Here, the authors provide a timely overview of the diverse linker classes in the published literature, along with their underlying design principles and overall influence on the properties and bioactivity of the associated PROTACs. Finally, the authors provide a critical analysis of current strategies for PROTAC assembly. The authors highlight important limitations associated with the traditional “trial and error” approach around linker design and selection, and suggest potential future avenues to further inform rational linker design and accelerate the identification of optimised PROTACs. In particular, the authors believe that advances in computational and structural methods will play an essential role to gain a better understanding of the structure and dynamics of PROTAC ternary complexes, and will be essential to address the current gaps in knowledge associated with PROTAC design. ,Robert I. Troup ... Matthias G. J. Baud [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [19] => Array ( [ArticleId] => 71 [Create_Time] => 2020-10-20 [zipUrl] => https://www.explorationpub.com/uploads/zip/202010/20201030105728.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100221/100221.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100221/100221.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100221/100221_cover.png [JournalsId] => 4 [Title] => Downregulation of 15-hydroxyprostaglandin dehydrogenase during acquired tamoxifen resistance and association with poor prognosis in ERα-positive breast cancer [Abstract] => Aim: Tamoxifen (TAM) resistance remains a clinical issue in breast cancer. The authors previously reported that 15-hydroxyprostaglandin dehydrogenase (HPGD) was significantly downregulated in tamox [AbstractComplete] =>Tamoxifen (TAM) resistance remains a clinical issue in breast cancer. The authors previously reported that 15-hydroxyprostaglandin dehydrogenase (HPGD) was significantly downregulated in tamoxifen-resistant (TAMr) breast cancer cell lines. Here, the authors investigated the relationship between HPGD expression, TAM resistance and prediction of outcome in breast cancer.
HPGD overexpression and silencing studies were performed in isogenic TAMr and parental human breast cancer cell lines to establish the impact of HPGD expression on TAM resistance. HPGD expression and clinical outcome relationships were explored using immunohistochemistry and in silico analysis.
Restoration of HPGD expression and activity sensitised TAMr MCF-7 cells to TAM and 17β-oestradiol, whilst HPGD silencing in parental MCF-7 cells reduced TAM sensitivity. TAMr cells released more prostaglandin E2 (PGE2) than controls, which was reduced in TAMr cells stably transfected with HPGD. Exogenous PGE2 signalled through the EP4 receptor to reduce breast cancer cell sensitivity to TAM. Decreased HPGD expression was associated with decreased overall survival in ERα-positive breast cancer patients.
HPGD downregulation in breast cancer is associated with reduced response to TAM therapy via PGE2-EP4 signalling and decreases patient survival. The data offer a potential target to develop combination therapies that may overcome acquired tamoxifen resistance.
Immunotherapy dramatically changed the management of several malignancies including non-small cell lung cancer (NSCLC). Since immune checkpoint inhibitors have a different mechanism of action from cytotoxic agents or small molecules against NSCLC, also tumor response may present with atypical features. Pseudoprogression (PP) is a distinct response pattern defined by a transient enlargement of the tumor burden, sustained by inflammatory cells and usually not associated with worsening of performance status (PS). Here the authors describe the case of a lung adenocarcinoma patient treated with pembrolizumab, who developed an early symptomatic PP with a dramatic global worsening of PS. Subsequently an improvement in general condition and a brilliant tumor response were observed. Tumor re-biopsy was collected after the treatment in order to support the identification of PP and to describe microenvironment modifications induce by immunotherapy.
[Names] => Giulia Meoni ... Angela Stefania Ribecco [Doi] => 10.37349/etat.2020.00022 [Published] => October 30, 2020 [Viewed] => 2626 [Downloaded] => 43 [Subject] => Case Report [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00022 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 34 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:372–380 [Recommend] => 0 [Keywords] => Non-small cell lung cancer, immunotherapy, pseudoprogression, performance status, kirsten rat sarcoma [DetailTitle] => Immunotherapy in Cancer Patients [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/34 [Id] => 100222 [ris] => https://www.explorationpub.com/uploads/Article/A100222/8059bd17c33e92ca6d6e133ac0cd7cca.ris [bib] => https://www.explorationpub.com/uploads/Article/A100222/e63ea39254800884fb4b8102019c65dc.bib [ens] => [Cited] => 0 [Cited_Time] => 2021-02-01 [CitethisArticle] => Meoni G, Decarli NL, Benucci M, Raspanti C, Ribecco AS. Pseudoprogression in lung cancer: a case report. Explor Target Antitumor Ther. 2020;1:372-80. https://doi.org/10.37349/etat.2020.00022 [Jindex] => 1 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Pseudoprogression in lung cancer: a case report, Non-small cell lung cancer, immunotherapy, pseudoprogression, performance status, kirsten rat sarcoma, Immunotherapy dramatically changed the management of several malignancies including non-small cell lung cancer (NSCLC). Since immune checkpoint inhibitors have a different mechanism of action from cytotoxic agents or small molecules against NSCLC, also tumor response may present with atypical features. Pseudoprogression (PP) is a distinct response pattern defined by a transient enlargement of the tumor burden, sustained by inflammatory cells and usually not associated with worsening of performance status (PS). Here the authors describe the case of a lung adenocarcinoma patient treated with pembrolizumab, who developed an early symptomatic PP with a dramatic global worsening of PS. Subsequently an improvement in general condition and a brilliant tumor response were observed. Tumor re-biopsy was collected after the treatment in order to support the identification of PP and to describe microenvironment modifications induce by immunotherapy. ,Giulia Meoni ... Angela Stefania Ribecco [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [21] => Array ( [ArticleId] => 74 [Create_Time] => 2020-10-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202010/20201030105315.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100219/100219.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100219/100219.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100219/100219_cover.png [JournalsId] => 4 [Title] => Potential of guggulsterone, a farnesoid X receptor antagonist, in the prevention and treatment of cancer [Abstract] => Cancer is one of the most dreadful diseases in the world with a mortality of 9.6 million annually. Despite the advances in diagnosis and treatment during the last couple of decades, it still remains [AbstractComplete] =>Cancer is one of the most dreadful diseases in the world with a mortality of 9.6 million annually. Despite the advances in diagnosis and treatment during the last couple of decades, it still remains a serious concern due to the limitations associated with currently available cancer management strategies. Therefore, alternative strategies are highly required to overcome these glitches. The importance of medicinal plants as primary healthcare has been well-known from time immemorial against various human diseases, including cancer. Commiphora wightii that belongs to Burseraceae family is one such plant which has been used to cure various ailments in traditional systems of medicine. This plant has diverse pharmacological properties such as antioxidant, antibacterial, antimutagenic, and antitumor which mostly owes to the presence of its active compound guggulsterone (GS) that exists in the form of Z- and E-isomers. Mounting evidence suggests that this compound has promising anticancer activities and was shown to suppress several cancer signaling pathways such as NF-κB/ERK/MAPK/AKT/STAT and modulate the expression of numerous signaling molecules such as the farnesoid X receptor, cyclin D1, survivin, caspases, HIF-1α, MMP-9, EMT proteins, tumor suppressor proteins, angiogenic proteins, and apoptotic proteins. The current review is an attempt to summarize the biological activities and diverse anticancer activities (both in vitro and in vivo) of the compound GS and its derivatives, along with its associated mechanism against various cancers.
[Names] => Sosmitha Girisa ... Ajaikumar B. Kunnumakkara [Doi] => 10.37349/etat.2020.00019 [Published] => October 30, 2020 [Viewed] => 3523 [Downloaded] => 69 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00019 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 31 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:313–342 [Recommend] => 0 [Keywords] => Cancer, Commiphora wightii, guggulsterone, Z and E isomers, anticancer activities [DetailTitle] => Targeting Transcription Factors for Cancer Therapy [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/31 [Id] => 100219 [ris] => https://www.explorationpub.com/uploads/Article/A100219/c8f76272c441a0e251b7596a445c29d4.ris [bib] => https://www.explorationpub.com/uploads/Article/A100219/bb3320b02820a623e58ef791771c2584.bib [ens] => [Cited] => 14 [Cited_Time] => 2024-04-27 [CitethisArticle] => Girisa S, Parama D, Harsha C, Banik K, Kunnumakkara AB. Potential of guggulsterone, a farnesoid X receptor antagonist, in the prevention and treatment of cancer. Explor Target Antitumor Ther. 2020;1:313-42. https://doi.org/10.37349/etat.2020.00019 [Jindex] => 1 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Potential of guggulsterone, a farnesoid X receptor antagonist, in the prevention and treatment of cancer, Cancer, Commiphora wightii, guggulsterone, Z and E isomers, anticancer activities, Cancer is one of the most dreadful diseases in the world with a mortality of 9.6 million annually. Despite the advances in diagnosis and treatment during the last couple of decades, it still remains a serious concern due to the limitations associated with currently available cancer management strategies. Therefore, alternative strategies are highly required to overcome these glitches. The importance of medicinal plants as primary healthcare has been well-known from time immemorial against various human diseases, including cancer. Commiphora wightii that belongs to Burseraceae family is one such plant which has been used to cure various ailments in traditional systems of medicine. This plant has diverse pharmacological properties such as antioxidant, antibacterial, antimutagenic, and antitumor which mostly owes to the presence of its active compound guggulsterone (GS) that exists in the form of Z- and E-isomers. Mounting evidence suggests that this compound has promising anticancer activities and was shown to suppress several cancer signaling pathways such as NF-κB/ERK/MAPK/AKT/STAT and modulate the expression of numerous signaling molecules such as the farnesoid X receptor, cyclin D1, survivin, caspases, HIF-1α, MMP-9, EMT proteins, tumor suppressor proteins, angiogenic proteins, and apoptotic proteins. The current review is an attempt to summarize the biological activities and diverse anticancer activities (both in vitro and in vivo) of the compound GS and its derivatives, along with its associated mechanism against various cancers. ,Sosmitha Girisa ... Ajaikumar B. Kunnumakkara [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [22] => Array ( [ArticleId] => 75 [Create_Time] => 2020-10-30 [zipUrl] => https://www.explorationpub.com/uploads/zip/202011/20201119114344.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100223/100223.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100223/100223.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100223/100223_cover.png [JournalsId] => 4 [Title] => Novel approaches for the rational design of PROTAC linkers [Abstract] => Proteolysis targeting chimeras (PROTACs) represent a promising class of hetero-bivalent molecules that facilitate ubiquitination of a target protein by simultaneously binding and bringing together b [AbstractComplete] =>Proteolysis targeting chimeras (PROTACs) represent a promising class of hetero-bivalent molecules that facilitate ubiquitination of a target protein by simultaneously binding and bringing together both the E3 enzyme and the target. These compounds consist of three structural components: two ligands one of which binds the protein of interest (POI) while the other binds an E3 ubiquitin ligase to promote POI ubiquitination, and a linker connecting both moieties. Recent developments in the field highlight the fact that linker composition and length play a crucial role in achieving optimal PROTAC properties, modulate binding kinetics and substantially impacts the potency and selectivity. In this review, the authors briefly discuss the recent findings in PROTAC design approaches with focus on the linker. For each PROTAC such linker parameters as chemical nature, length, hydrophilicity and rigidity have to be optimized to achieve improved stability, bioavailability cell membrane permeability and suitable spatial orientation between the target POI and the E3 ubiquitin ligase. Thus rational linker design with respect to composition, length and attachment sites is essential for the development of potent PROTAC compounds. Computer-aided design and novel innovative linker strategies, such as PROTAC shortening, photo-switchable PROTACs, in-cell click-formed CLIPTACs, “click chemistry” approaches are also discussed in the review.
[Names] => Almaz Zagidullin ... Emil Bulatov [Doi] => 10.37349/etat.2020.00023 [Published] => October 30, 2020 [Viewed] => 5391 [Downloaded] => 379 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00023 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 27 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:381–390 [Recommend] => 0 [Keywords] => PROTAC, protein degradation, linker chemistry [DetailTitle] => Proteolysis Targeting Chimera (PROTAC) [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/27 [Id] => 100223 [ris] => https://www.explorationpub.com/uploads/Article/A100223/64acc6a98be4f3eb3f9f3f31317fc7c1.ris [bib] => https://www.explorationpub.com/uploads/Article/A100223/a7fb84c0d6c26864f60455d2dc3d33b0.bib [ens] => [Cited] => 17 [Cited_Time] => 2024-04-27 [CitethisArticle] => Zagidullin A, Milyukov V, Rizvanov A, Bulatov E. Novel approaches for the rational design of PROTAC linkers. Explor Target Antitumor Ther. 2020;1:381-90. https://doi.org/10.37349/etat.2020.00023 [Jindex] => 1 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Novel approaches for the rational design of PROTAC linkers, PROTAC, protein degradation, linker chemistry, Proteolysis targeting chimeras (PROTACs) represent a promising class of hetero-bivalent molecules that facilitate ubiquitination of a target protein by simultaneously binding and bringing together both the E3 enzyme and the target. These compounds consist of three structural components: two ligands one of which binds the protein of interest (POI) while the other binds an E3 ubiquitin ligase to promote POI ubiquitination, and a linker connecting both moieties. Recent developments in the field highlight the fact that linker composition and length play a crucial role in achieving optimal PROTAC properties, modulate binding kinetics and substantially impacts the potency and selectivity. In this review, the authors briefly discuss the recent findings in PROTAC design approaches with focus on the linker. For each PROTAC such linker parameters as chemical nature, length, hydrophilicity and rigidity have to be optimized to achieve improved stability, bioavailability cell membrane permeability and suitable spatial orientation between the target POI and the E3 ubiquitin ligase. Thus rational linker design with respect to composition, length and attachment sites is essential for the development of potent PROTAC compounds. Computer-aided design and novel innovative linker strategies, such as PROTAC shortening, photo-switchable PROTACs, in-cell click-formed CLIPTACs, “click chemistry” approaches are also discussed in the review. ,Almaz Zagidullin ... Emil Bulatov [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [23] => Array ( [ArticleId] => 80 [Create_Time] => 2020-11-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202012/20201229031903.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100224/100224.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100224/100224.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100224/100224_cover.png [JournalsId] => 4 [Title] => Use of liquid biopsy in monitoring therapeutic resistance in EGFR oncogene addicted NSCLC [Abstract] => Liquid biopsy has emerged as a minimally invasive alternative to tumor tissue analysis for the management of lung cancer patients, especially for epidermal growth factor receptor (EGFR) oncogene add [AbstractComplete] =>Liquid biopsy has emerged as a minimally invasive alternative to tumor tissue analysis for the management of lung cancer patients, especially for epidermal growth factor receptor (EGFR) oncogene addicted tumor. In these patients, despite the clear benefits of tyrosine kinase inhibitors therapy, the development of acquired resistance and progressive disease is inevitable in most cases and liquid biopsy is important for molecular characterization at resistance and, being non-invasive, may be useful for disease monitoring. In this review, the authors will focus on the applications of liquid biopsy in EGFR-mutated non small cells lung cancer at diagnosis, during treatment and at progression, describing available data and possible future scenarios.
[Names] => Marialucia Iacovino ... Francesca Sparano [Doi] => 10.37349/etat.2020.00024 [Published] => December 28, 2020 [Viewed] => 2313 [Downloaded] => 62 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00024 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 23 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:391–400 [Recommend] => 0 [Keywords] => Liquid biopsy, non small cells lung cancer, osimertinib, EGFR resistance, T790M [DetailTitle] => Liquid Biopsy in Thoracic Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/23 [Id] => 100224 [ris] => https://www.explorationpub.com/uploads/Article/A100224/f16bad2ebdfc99f7a9613110561274df.ris [bib] => https://www.explorationpub.com/uploads/Article/A100224/df356b81db96d916801a8da2cd28417b.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-26 [CitethisArticle] => Iacovino M, Ciaramella V, Paragliola F, Suarato G, Busiello G, Sparano F. Use of liquid biopsy in monitoring therapeutic resistance in EGFR oncogene addicted NSCLC. Explor Target Antitumor Ther. 2020;1:391-400. https://doi.org/10.37349/etat.2020.00024 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Use of liquid biopsy in monitoring therapeutic resistance in EGFR oncogene addicted NSCLC, Liquid biopsy, non small cells lung cancer, osimertinib, EGFR resistance, T790M, Liquid biopsy has emerged as a minimally invasive alternative to tumor tissue analysis for the management of lung cancer patients, especially for epidermal growth factor receptor (EGFR) oncogene addicted tumor. In these patients, despite the clear benefits of tyrosine kinase inhibitors therapy, the development of acquired resistance and progressive disease is inevitable in most cases and liquid biopsy is important for molecular characterization at resistance and, being non-invasive, may be useful for disease monitoring. In this review, the authors will focus on the applications of liquid biopsy in EGFR-mutated non small cells lung cancer at diagnosis, during treatment and at progression, describing available data and possible future scenarios. ,Marialucia Iacovino ... Francesca Sparano [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [24] => Array ( [ArticleId] => 83 [Create_Time] => 2020-12-04 [zipUrl] => https://www.explorationpub.com/uploads/zip/202012/20201229032330.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100225/100225.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100225/100225.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100225/100225_cover.png [JournalsId] => 4 [Title] => Targeting transcription factors in cancer drug discovery [Abstract] => Cancer drug discovery is currently dominated by clinical trials or clinical research. Several potential drug candidates have been brought into the pipeline of drug discovery after showing very promi [AbstractComplete] =>Cancer drug discovery is currently dominated by clinical trials or clinical research. Several potential drug candidates have been brought into the pipeline of drug discovery after showing very promising results at the pre-clinical level and are waiting to be tested in human clinical trials. Interestingly, among the potential drug candidates, a few of them have targeted transcription factors highlighting the fundamental undruggable nature of these molecules. However, using advanced technologies, researchers were recently successful in partly unlocking this undruggable nature, which was considered as a ‘grey area’ in the early days of drug discovery, and as a result, several potential candidates have emerged recently. The purpose of the review is to highlight some of the recently reported studies of targeting transcription factors in cancer and their promising outcomes.
[Names] => Partha Mitra [Doi] => 10.37349/etat.2020.00025 [Published] => December 28, 2020 [Viewed] => 3982 [Downloaded] => 199 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00025 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 31 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:401–412 [Recommend] => 0 [Keywords] => Transcription factor, drug discovery, gene expression, protein-protein interaction [DetailTitle] => Targeting Transcription Factors for Cancer Therapy [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/31 [Id] => 100225 [ris] => https://www.explorationpub.com/uploads/Article/A100225/2c25ef66518707d84bf3201ce21e6ad6.ris [bib] => https://www.explorationpub.com/uploads/Article/A100225/996a2b8f570f523ee489e3b7fa4d965a.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-27 [CitethisArticle] => Mitra P. Targeting transcription factors in cancer drug discovery. Explor Target Antitumor Ther. 2020;1:401-12. https://doi.org/10.37349/etat.2020.00025 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Targeting transcription factors in cancer drug discovery, Transcription factor, drug discovery, gene expression, protein-protein interaction, Cancer drug discovery is currently dominated by clinical trials or clinical research. Several potential drug candidates have been brought into the pipeline of drug discovery after showing very promising results at the pre-clinical level and are waiting to be tested in human clinical trials. Interestingly, among the potential drug candidates, a few of them have targeted transcription factors highlighting the fundamental undruggable nature of these molecules. However, using advanced technologies, researchers were recently successful in partly unlocking this undruggable nature, which was considered as a ‘grey area’ in the early days of drug discovery, and as a result, several potential candidates have emerged recently. The purpose of the review is to highlight some of the recently reported studies of targeting transcription factors in cancer and their promising outcomes. ,Partha Mitra [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [25] => Array ( [ArticleId] => 86 [Create_Time] => 2020-12-21 [zipUrl] => https://www.explorationpub.com/uploads/zip/202103/20210309012929.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100226/100226.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100226/100226.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100226/100226_cover.png [JournalsId] => 4 [Title] => An overview of the potential anticancer properties of cardamonin [Abstract] => Cancer is one of the leading causes of mortality, contributing to 9.6 million deaths globally in 2018 alone. Although several cancer treatments exist, they are often associated with severe side effe [AbstractComplete] =>Cancer is one of the leading causes of mortality, contributing to 9.6 million deaths globally in 2018 alone. Although several cancer treatments exist, they are often associated with severe side effects and high toxicities, leaving room for significant advancements to be made in the field. In recent years, several phytochemicals from plants and natural bioresources have been extracted and tested against various human malignancies using both in vitro and in vivo preclinical model systems. Cardamonin, a chalcone extracted from the Alpinia species, is an example of a natural therapeutic agent that has anti-cancer and anti-inflammatory effects against human cancer cell lines, including breast, lung, colon, and gastric, in both in vitro culture systems as well as xenograft mouse models. Earlier, cardamonin was used as a natural medicine against stomach related issues, diarrhea, insulin resistance, nephroprotection against cisplatin treatment, vasorelaxant and antinociceptive. The compound is well-known to inhibit proliferation, migration, invasion, and induce apoptosis, through the involvement of Wnt/β-catenin, NF-κB, and PI3K/Akt pathways. The good biosafety and pharmacokinetic profiling of cardamonin satisfy it as an attractive molecule for the development of an anticancer agent. The present review has summarized the chemo-preventive ability of cardamonin as an anticancer agent against numerous human malignancies.
[Names] => Shanaya Ramchandani ... Manoj Garg [Doi] => 10.37349/etat.2020.00026 [Published] => December 28, 2020 [Viewed] => 3427 [Downloaded] => 57 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00026 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 31 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:413–426 [Recommend] => 0 [Keywords] => Cancer, cardamonin, chalcone, apoptosis, proliferation, Wnt/β-catenin, NF-κB, PI3K/Akt [DetailTitle] => Targeting Transcription Factors for Cancer Therapy [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/31 [Id] => 100226 [ris] => https://www.explorationpub.com/uploads/Article/A100226/52c07e24f4df7c32e19ecd1db76756d4.ris [bib] => https://www.explorationpub.com/uploads/Article/A100226/f284e8b1df67388db9aac7ea091c56b8.bib [ens] => [Cited] => 5 [Cited_Time] => 2024-04-27 [CitethisArticle] => Ramchandani S, Naz I, Dhudha N, Garg M. An overview of the potential anticancer properties of cardamonin. Explor Target Antitumor Ther. 2020;1:413-26. https://doi.org/10.37349/etat.2020.00026 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => An overview of the potential anticancer properties of cardamonin, Cancer, cardamonin, chalcone, apoptosis, proliferation, Wnt/β-catenin, NF-κB, PI3K/Akt, Cancer is one of the leading causes of mortality, contributing to 9.6 million deaths globally in 2018 alone. Although several cancer treatments exist, they are often associated with severe side effects and high toxicities, leaving room for significant advancements to be made in the field. In recent years, several phytochemicals from plants and natural bioresources have been extracted and tested against various human malignancies using both in vitro and in vivo preclinical model systems. Cardamonin, a chalcone extracted from the Alpinia species, is an example of a natural therapeutic agent that has anti-cancer and anti-inflammatory effects against human cancer cell lines, including breast, lung, colon, and gastric, in both in vitro culture systems as well as xenograft mouse models. Earlier, cardamonin was used as a natural medicine against stomach related issues, diarrhea, insulin resistance, nephroprotection against cisplatin treatment, vasorelaxant and antinociceptive. The compound is well-known to inhibit proliferation, migration, invasion, and induce apoptosis, through the involvement of Wnt/β-catenin, NF-κB, and PI3K/Akt pathways. The good biosafety and pharmacokinetic profiling of cardamonin satisfy it as an attractive molecule for the development of an anticancer agent. The present review has summarized the chemo-preventive ability of cardamonin as an anticancer agent against numerous human malignancies. ,Shanaya Ramchandani ... Manoj Garg [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [26] => Array ( [ArticleId] => 90 [Create_Time] => 2020-12-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202201/20220111084715.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100227/100227.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100227/100227.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100227/100227_cover.png [JournalsId] => 4 [Title] => Is hyperprogressive disease a specific phenomenom of immunotherapy? [Abstract] => Hyperprogressive disease (HPD) is a novel pattern of response during immunotherapy treatment. Several retrospective studies have evaluated its prevalence among various cancer types and, in particula [AbstractComplete] =>Hyperprogressive disease (HPD) is a novel pattern of response during immunotherapy treatment. Several retrospective studies have evaluated its prevalence among various cancer types and, in particular, in non-small cell lung cancer patients, based on different definition criteria. If HPD is a just a typical phenomenon of immunotherapy is still an unsolved concern. This paper summarized the available data about HPD in other cancer treatments.
[Names] => Marta Brambilla ... Mario Occhipinti [Doi] => 10.37349/etat.2020.00027 [Published] => December 28, 2020 [Viewed] => 2001 [Downloaded] => 29 [Subject] => Letter to the Editor [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00027 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 34 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:427–433 [Recommend] => 0 [Keywords] => Hyperprogressive disease, immunotherapy, chemotherapy-immunotherapy [DetailTitle] => Immunotherapy in Cancer Patients [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/34 [Id] => 100227 [ris] => https://www.explorationpub.com/uploads/Article/A100227/05b7f614ca54568aa8efce32e8b6e624.ris [bib] => https://www.explorationpub.com/uploads/Article/A100227/5d57c88db1b9cfbccec3f247af19da33.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Brambilla M, Lo Russo G, Ferrara R, Manglaviti S, Garassino MC, Occhipinti M. Is hyperprogressive disease a specific phenomenom of immunotherapy. Explor Target Antitumor Ther. 2020;1:427-33. https://doi.org/10.37349/etat.2020.00027 [Jindex] => 0 [CName] => MarioOcchipinti, [CEmail] => mario.occhipinti@istitutotumori.mi.it, [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Is hyperprogressive disease a specific phenomenom of immunotherapy?, Hyperprogressive disease, immunotherapy, chemotherapy-immunotherapy, Hyperprogressive disease (HPD) is a novel pattern of response during immunotherapy treatment. Several retrospective studies have evaluated its prevalence among various cancer types and, in particular, in non-small cell lung cancer patients, based on different definition criteria. If HPD is a just a typical phenomenon of immunotherapy is still an unsolved concern. This paper summarized the available data about HPD in other cancer treatments. ,Marta Brambilla ... Mario Occhipinti [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [27] => Array ( [ArticleId] => 91 [Create_Time] => 2020-12-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202102/20210208061057.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100228/100228.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100228/100228.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100228/100228_cover.png [JournalsId] => 4 [Title] => Circulating biomarkers in malignant pleural mesothelioma [Abstract] => Malignant pleural mesothelioma (MPM) is an aggressive tumor strictly connected to asbestos exposure. Prognosis is dismal as diagnosis commonly occurs in advanced stage. Radiological screenings have [AbstractComplete] =>Malignant pleural mesothelioma (MPM) is an aggressive tumor strictly connected to asbestos exposure. Prognosis is dismal as diagnosis commonly occurs in advanced stage. Radiological screenings have not proven to be effective and also pathological diagnosis may be challenging. In the era of precision oncology, validation of robust non-invasive biomarkers for screening of asbestos-exposed individuals, assessment of prognosis and prediction of response to treatments remains an important unmet clinical need. This review provides an overview on current understanding and possible applications of liquid biopsy in MPM, mostly focused on the utility as diagnostic and prognostic test.
[Names] => Giuseppe Viscardi ... Giulia Galli [Doi] => 10.37349/etat.2020.00028 [Published] => December 28, 2020 [Viewed] => 2742 [Downloaded] => 64 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00028 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 23 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:434–451 [Recommend] => 0 [Keywords] => Mesothelioma, malignant pleural mesothelioma, liquid biopsy, biomarkers, mesothelin, miRNAs, CTC, ctDNA [DetailTitle] => Liquid Biopsy in Thoracic Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/23 [Id] => 100228 [ris] => https://www.explorationpub.com/uploads/Article/A100228/f618889fe22f3fa2ba86550fa8739361.ris [bib] => https://www.explorationpub.com/uploads/Article/A100228/e96540bd3c469063658d11e1b818cf9e.bib [ens] => [Cited] => 5 [Cited_Time] => 2024-04-26 [CitethisArticle] => Viscardi G, Di Natale D, Fasano M, Brambilla M, Lobefaro R, De Toma A, et al. Circulating biomarkers in malignant pleural mesothelioma. Explor Target Antitumor Ther. 2020;1:434-51. https://doi.org/10.37349/etat.2020.00028 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Circulating biomarkers in malignant pleural mesothelioma, Mesothelioma, malignant pleural mesothelioma, liquid biopsy, biomarkers, mesothelin, miRNAs, CTC, ctDNA, Malignant pleural mesothelioma (MPM) is an aggressive tumor strictly connected to asbestos exposure. Prognosis is dismal as diagnosis commonly occurs in advanced stage. Radiological screenings have not proven to be effective and also pathological diagnosis may be challenging. In the era of precision oncology, validation of robust non-invasive biomarkers for screening of asbestos-exposed individuals, assessment of prognosis and prediction of response to treatments remains an important unmet clinical need. This review provides an overview on current understanding and possible applications of liquid biopsy in MPM, mostly focused on the utility as diagnostic and prognostic test. ,Giuseppe Viscardi ... Giulia Galli [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [28] => Array ( [ArticleId] => 92 [Create_Time] => 2020-12-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202012/20201229095840.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100229/100229.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100229/100229.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100229/100229_cover.png [JournalsId] => 4 [Title] => An overview of immune checkpoint inhibitors in breast cancer [Abstract] => Although breast cancer is not traditionally considered an immunogenic type of tumor, the combination of immunotherapy and chemotherapy has recently emerged as a novel treatment option in triple-nega [AbstractComplete] =>Although breast cancer is not traditionally considered an immunogenic type of tumor, the combination of immunotherapy and chemotherapy has recently emerged as a novel treatment option in triple-negative subtype in the advanced setting and other similar combinations of immune checkpoint inhibitors with chemotherapy are expected to become part of the neoadjuvant management in the near future. In addition, encouraging results have been observed with the combination of immune checkpoint blockade with diverse biological agents, including anti-HER2 agents, CDK 4/6 inhibitors, PARP-inhibitors. The present review summarized the available evidence coming from clinical trials on the role of immune checkpoint inhibitors in the management of breast cancer, both in advanced and early setting.
[Names] => Federica Miglietta ... Nicla La Verde [Doi] => 10.37349/etat.2020.00029 [Published] => December 28, 2020 [Viewed] => 3432 [Downloaded] => 110 [Subject] => Review [Year] => 2020 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2020.00029 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 34 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2020;1:452–472 [Recommend] => 0 [Keywords] => Early breast cancer, metastatic breast cancer, immunotherapy, immune checkpoint inhibitors [DetailTitle] => Immunotherapy in Cancer Patients [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/34 [Id] => 100229 [ris] => https://www.explorationpub.com/uploads/Article/A100229/750df53fcbcb2ef2765ccf4cf0f905bc.ris [bib] => https://www.explorationpub.com/uploads/Article/A100229/4aa18589d55f5973c8a8505464a5e103.bib [ens] => [Cited] => 4 [Cited_Time] => 2024-04-26 [CitethisArticle] => Miglietta F, Cona MS, Dieci MV, Guarneri V, La Verde N. An overview of immune checkpoint inhibitors in breast cancer. Explor Target Antitumor Ther. 2020;1:452-72. https://doi.org/10.37349/etat.2020.00029 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => An overview of immune checkpoint inhibitors in breast cancer, Early breast cancer, metastatic breast cancer, immunotherapy, immune checkpoint inhibitors, Although breast cancer is not traditionally considered an immunogenic type of tumor, the combination of immunotherapy and chemotherapy has recently emerged as a novel treatment option in triple-negative subtype in the advanced setting and other similar combinations of immune checkpoint inhibitors with chemotherapy are expected to become part of the neoadjuvant management in the near future. In addition, encouraging results have been observed with the combination of immune checkpoint blockade with diverse biological agents, including anti-HER2 agents, CDK 4/6 inhibitors, PARP-inhibitors. The present review summarized the available evidence coming from clinical trials on the role of immune checkpoint inhibitors in the management of breast cancer, both in advanced and early setting. ,Federica Miglietta ... Nicla La Verde [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [29] => Array ( [ArticleId] => 97 [Create_Time] => 2021-01-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202305/20230525061009.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100230/100230.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100230/100230.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100230/100230_cover.png [JournalsId] => 4 [Title] => Old but gold: the role of drug combinations in improving response to immune check-point inhibitors in thoracic malignancies beyond NSCLC [Abstract] => The introduction of immune checkpoint inhibitors (ICIs) in non-oncogene addicted non-small cell lung cancer (NSCLC) has revolutionized the treatment scenario and led to a meaningful improvement in p [AbstractComplete] =>The introduction of immune checkpoint inhibitors (ICIs) in non-oncogene addicted non-small cell lung cancer (NSCLC) has revolutionized the treatment scenario and led to a meaningful improvement in patient prognosis. Disappointingly, the success of ICI therapy in NSCLC has not been fully replicated in other thoracic malignancies as small cell lung cancer (SCLC), malignant pleural mesothelioma (MPM), and thymic epithelial tumors (TETs), due to the peculiar biological features of these disease and to the difficulties in the conduction of well-designed, biomarker-driven clinical trials. Therefore, combination strategies of ICIs plus conventional therapies (either chemotherapy, alternative ICIs or targeted agents) have been implemented. Although first approvals of ICI therapy have been recently granted in SCLC and MPM (in combination with chemotherapy and different ICIs), results remain somewhat modest and limited to a small proportion of patients. This work reviews the trial results of ICI therapy in mesothelioma, SCLC, and TETs and discusses the potential of combining ICIs with old drugs.
[Names] => Luca Cantini ... Rossana Berardi [Doi] => 10.37349/etat.2021.00030 [Published] => February 28, 2021 [Viewed] => 2061 [Downloaded] => 36 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00030 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 34 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:1–25 [Recommend] => 0 [Keywords] => Immune checkpoint inhibitors, small cell lung cancer, mesothelioma, thymic epithelial tumor, immuno-oncology, immune modulating [DetailTitle] => Immunotherapy in Cancer Patients [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/34# [Id] => 100230 [ris] => https://www.explorationpub.com/uploads/Article/A100230/268b7b5dcb9340d1928114a689ad3b69.ris [bib] => https://www.explorationpub.com/uploads/Article/A100230/aef771f2d4d8a6efc3e9386442a9ccbf.bib [ens] => [Cited] => 0 [Cited_Time] => 2021-02-01 [CitethisArticle] => Cantini L, Pecci F, Merloni F, Lanese A, Lenci E, Paoloni F, et al. Old but gold: the role of drug combinations in improving response to immune check-point inhibitors in thoracic malignancies beyond NSCLC. Explor Target Antitumor Ther. 2021;2:1-25. https://doi.org/10.37349/etat.2021.00030 [Jindex] => 0 [CName] => RossanaBerardi, [CEmail] => rossana.berardi.it@gmail.com, [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Old but gold: the role of drug combinations in improving response to immune check-point inhibitors in thoracic malignancies beyond NSCLC, Immune checkpoint inhibitors, small cell lung cancer, mesothelioma, thymic epithelial tumor, immuno-oncology, immune modulating, The introduction of immune checkpoint inhibitors (ICIs) in non-oncogene addicted non-small cell lung cancer (NSCLC) has revolutionized the treatment scenario and led to a meaningful improvement in patient prognosis. Disappointingly, the success of ICI therapy in NSCLC has not been fully replicated in other thoracic malignancies as small cell lung cancer (SCLC), malignant pleural mesothelioma (MPM), and thymic epithelial tumors (TETs), due to the peculiar biological features of these disease and to the difficulties in the conduction of well-designed, biomarker-driven clinical trials. Therefore, combination strategies of ICIs plus conventional therapies (either chemotherapy, alternative ICIs or targeted agents) have been implemented. Although first approvals of ICI therapy have been recently granted in SCLC and MPM (in combination with chemotherapy and different ICIs), results remain somewhat modest and limited to a small proportion of patients. This work reviews the trial results of ICI therapy in mesothelioma, SCLC, and TETs and discusses the potential of combining ICIs with old drugs. ,Luca Cantini ... Rossana Berardi [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [30] => Array ( [ArticleId] => 100 [Create_Time] => 2021-02-10 [zipUrl] => https://www.explorationpub.com/uploads/zip/202102/20210228100237.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100231/100231.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100231/100231.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100231/100231_cover.png [JournalsId] => 4 [Title] => Emerging role of pioneer transcription factors in targeted ERα positive breast cancer [Abstract] => Transcription factors (TFs) are modular protein groups that preferably bind to DNA sequences and guide genomic expression through transcription. Among these key regulators, “pioneer facto [AbstractComplete] =>Transcription factors (TFs) are modular protein groups that preferably bind to DNA sequences and guide genomic expression through transcription. Among these key regulators, “pioneer factors” are an emerging class of TFs that specifically interact with nucleosomal DNA and facilitate accessible genomic binding sites for the additional TFs. There is growing evidence of these specialized modulators in particular malignancies, as highlighted by agents’ clinical efficacy, specifically targeting nuclear hormone receptors. They have been implicated in multiple cancers more recently, with a high proportion inculpating on hormone influential cancers. Moreover, extended crosstalk and cooperation between ERα pioneering factors in estrogen-dependent breast cancer (BC) remain elucidated. This review discusses on the recent advances in our understanding of pioneer TFs in cancer, especially highlighting its potentiality to modulate chromatin condensation to permit ERα recruitment in BC cells. Through the study it was concluded that the highly prospected pioneer TFs in BC, including FOXA1, TLE1, PBX1, and GATA3, possess the potential therapeutic significance and further innovations in the field could yield targeted therapy in cancer treatment.
[Names] => Honey Pavithran, Ranjith Kumavath [Doi] => 10.37349/etat.2021.00031 [Published] => February 28, 2021 [Viewed] => 2560 [Downloaded] => 59 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00031 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 31 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:26–35 [Recommend] => 0 [Keywords] => Transcription factor, pioneer transcription factors, ERα signaling, breast cancer [DetailTitle] => Targeting Transcription Factors for Cancer Therapy [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/31 [Id] => 100231 [ris] => https://www.explorationpub.com/uploads/Article/A100231/f7fe6e09bf32b3405e4220386e164e91.ris [bib] => https://www.explorationpub.com/uploads/Article/A100231/3a51d27f909c01132bdc107d20183f21.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Pavithran H, Kumavath R. Emerging role of pioneer transcription factors in targeted ERα positive breast cancer. Explor Target Antitumor Ther. 2021;2:26-35. https://doi.org/10.37349/etat.2021.00031 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Emerging role of pioneer transcription factors in targeted ERα positive breast cancer, Transcription factor, pioneer transcription factors, ERα signaling, breast cancer, Transcription factors (TFs) are modular protein groups that preferably bind to DNA sequences and guide genomic expression through transcription. Among these key regulators, “pioneer factors” are an emerging class of TFs that specifically interact with nucleosomal DNA and facilitate accessible genomic binding sites for the additional TFs. There is growing evidence of these specialized modulators in particular malignancies, as highlighted by agents’ clinical efficacy, specifically targeting nuclear hormone receptors. They have been implicated in multiple cancers more recently, with a high proportion inculpating on hormone influential cancers. Moreover, extended crosstalk and cooperation between ERα pioneering factors in estrogen-dependent breast cancer (BC) remain elucidated. This review discusses on the recent advances in our understanding of pioneer TFs in cancer, especially highlighting its potentiality to modulate chromatin condensation to permit ERα recruitment in BC cells. Through the study it was concluded that the highly prospected pioneer TFs in BC, including FOXA1, TLE1, PBX1, and GATA3, possess the potential therapeutic significance and further innovations in the field could yield targeted therapy in cancer treatment. ,Honey Pavithran, Ranjith Kumavath [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [31] => Array ( [ArticleId] => 102 [Create_Time] => 2021-02-19 [zipUrl] => https://www.explorationpub.com/uploads/zip/202102/20210228103050.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100233/100233.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100233/100233.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100233/cover.png [JournalsId] => 4 [Title] => Immunotherapy in gynecological cancers [Abstract] => Immunotherapy has changed the natural history of several malignancies that, a decade ago, had a very poor prognosis, such as lung cancer and melanoma. Consequently, many attempts have been done to e [AbstractComplete] =>Immunotherapy has changed the natural history of several malignancies that, a decade ago, had a very poor prognosis, such as lung cancer and melanoma. Consequently, many attempts have been done to expand the indications of immunotherapy agents, predominantly immune checkpoint inhibitors (ICIs), in other cancers, including gynecological malignancies. Alongside promising results in cervical and endometrial neoplasms, there are not clear data on the benefit of ICIs as single agent or in combination with antiangiogenic agents in ovarian cancer (OC) and ongoing trials are focusing on combining ICIs with standard chemotherapy or PARP inhibitors. This chapter summarized the evidences of ICIs in gynecological malignancies and report the ongoing trials in cervical, endometrial and OC.
[Names] => Domenica Lorusso ... Giovanni Scambia [Doi] => 10.37349/etat.2021.00033 [Published] => February 28, 2021 [Viewed] => 1853 [Downloaded] => 42 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00033 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 34 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:48–64 [Recommend] => 0 [Keywords] => Immunotherapy, ovarian cancer, endometrial cancer, cervical cancer [DetailTitle] => Immunotherapy in Cancer Patients [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/34 [Id] => 100233 [ris] => https://www.explorationpub.com/uploads/Article/A100233/e19df4f5717c0fecb8c262cd7b59ab84.ris [bib] => https://www.explorationpub.com/uploads/Article/A100233/c5bfe4e7bd5e34959b6f80e11e4bafa0.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Lorusso D, Ceni V, Daniele G, Pietragalla A, Salutari V, Muratore M, et al. Immunotherapy in gynecological cancers. Explor Target Antitumor Ther. 2021;2:48-64. https://doi.org/10.37349/etat.2021.00033 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Immunotherapy in gynecological cancers, Immunotherapy, ovarian cancer, endometrial cancer, cervical cancer, Immunotherapy has changed the natural history of several malignancies that, a decade ago, had a very poor prognosis, such as lung cancer and melanoma. Consequently, many attempts have been done to expand the indications of immunotherapy agents, predominantly immune checkpoint inhibitors (ICIs), in other cancers, including gynecological malignancies. Alongside promising results in cervical and endometrial neoplasms, there are not clear data on the benefit of ICIs as single agent or in combination with antiangiogenic agents in ovarian cancer (OC) and ongoing trials are focusing on combining ICIs with standard chemotherapy or PARP inhibitors. This chapter summarized the evidences of ICIs in gynecological malignancies and report the ongoing trials in cervical, endometrial and OC. ,Domenica Lorusso ... Giovanni Scambia [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [32] => Array ( [ArticleId] => 104 [Create_Time] => 2021-02-19 [zipUrl] => https://www.explorationpub.com/uploads/zip/202103/20210325040852.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100232/100232.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100232/100232.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100232/cover.png [JournalsId] => 4 [Title] => Non-invasive detection of epithelial mesenchymal transition phenotype and metastatic dissemination of lung cancer by liquid biopsy [Abstract] => The occurrence of phenotype switch from an epithelial to a mesenchymal cell state during the activation of the epithelial mesenchymal transition (EMT) program in cancer cells has been closely associ [AbstractComplete] =>The occurrence of phenotype switch from an epithelial to a mesenchymal cell state during the activation of the epithelial mesenchymal transition (EMT) program in cancer cells has been closely associated with the generation of invasive tumor cells that contribute to metastatic dissemination and treatment failure. Liquid biopsy represents an emergent non-invasive tool that may improve our understanding of the molecular events leading to cancer progression and initiating the metastatic cascade through the dynamic analysis of tumor-derived components isolated from body fluids. The present review will primarily focus on the applications of liquid biopsy in lung cancer patients for identifying EMT signature, elucidating molecular mechanisms underlying the acquisition of an invasive phenotype and detecting new targets for therapy.
[Names] => Viviana De Rosa ... Francesca Iommelli [Doi] => 10.37349/etat.2021.00032 [Published] => February 28, 2021 [Viewed] => 1671 [Downloaded] => 32 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00032 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 23 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:36–47 [Recommend] => 0 [Keywords] => EMT, metastatic dissemination, lung cancer, liquid biopsy [DetailTitle] => Liquid Biopsy in Thoracic Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/23 [Id] => 100232 [ris] => https://www.explorationpub.com/uploads/Article/A100232/12f22533a0077792c7dc928406e00c99.ris [bib] => https://www.explorationpub.com/uploads/Article/A100232/67e61c96b2c666db302d268b0cdfeac4.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => De Rosa V, Fonti R, Del Vecchio S, Iommelli F. Non-invasive detection of epithelial mesenchymal transition phenotype and metastatic dissemination of lung cancer by liquid biopsy. Explor Target Antitumor Ther. 2021;2:36-47. https://doi.org/10.37349/etat.2021.00032 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Non-invasive detection of epithelial mesenchymal transition phenotype and metastatic dissemination of lung cancer by liquid biopsy, EMT, metastatic dissemination, lung cancer, liquid biopsy, The occurrence of phenotype switch from an epithelial to a mesenchymal cell state during the activation of the epithelial mesenchymal transition (EMT) program in cancer cells has been closely associated with the generation of invasive tumor cells that contribute to metastatic dissemination and treatment failure. Liquid biopsy represents an emergent non-invasive tool that may improve our understanding of the molecular events leading to cancer progression and initiating the metastatic cascade through the dynamic analysis of tumor-derived components isolated from body fluids. The present review will primarily focus on the applications of liquid biopsy in lung cancer patients for identifying EMT signature, elucidating molecular mechanisms underlying the acquisition of an invasive phenotype and detecting new targets for therapy. ,Viviana De Rosa ... Francesca Iommelli [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [33] => Array ( [ArticleId] => 107 [Create_Time] => 2021-02-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202102/20210228084954.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100234/100234.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100234/100234.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100234/100234_cover.png [JournalsId] => 4 [Title] => Multi-omics tumor profiling technologies to develop precision medicine in multiple myeloma [Abstract] => Multiple myeloma (MM), the second most common hematologic cancer, is caused by accumulation of aberrant plasma cells in the bone marrow. Its molecular causes are not fully understood and its great h [AbstractComplete] =>Multiple myeloma (MM), the second most common hematologic cancer, is caused by accumulation of aberrant plasma cells in the bone marrow. Its molecular causes are not fully understood and its great heterogeneity among patients complicates therapeutic decision-making. In the past decades, development of new therapies and drugs have significantly improved survival of MM patients. However, resistance to drugs and relapse remain the most common causes of mortality and are the major challenges to overcome. The advent of high throughput omics technologies capable of analyzing big amount of clinical and biological data has changed the way to diagnose and treat MM. Integration of omics data (gene mutations, gene expression, epigenetic information, and protein and metabolite levels) with clinical histories of thousands of patients allows to build scores to stratify the risk at diagnosis and predict the response to treatment, helping clinicians to make better educated decisions for each particular case. There is no doubt that the future of MM treatment relies on personalized therapies based on predictive models built from omics studies. This review summarizes the current treatments and the use of omics technologies in MM, and their importance in the implementation of personalized medicine.
[Names] => Sara Ovejero, Jerome Moreaux [Doi] => 10.37349/etat.2021.00034 [Published] => February 28, 2021 [Viewed] => 3029 [Downloaded] => 58 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00034 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 32 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:65–106 [Recommend] => 0 [Keywords] => Multiple myeloma, omics data, drugs, biomarkers, predictive models, personalized medicine [DetailTitle] => Off-Label Drugs and -Omics Data in Cancer Treatment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/32 [Id] => 100234 [ris] => https://www.explorationpub.com/uploads/Article/A100234/c675206781d428a99da4793fcf893eb5.ris [bib] => https://www.explorationpub.com/uploads/Article/A100234/dacd76ae6a20bebe64732c89cf222c08.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Ovejero S, Moreaux J. Multi-omics tumor profiling technologies to develop precision medicine in multiple myeloma. Explor Target Antitumor Ther. 2021;2:65-106. https://doi.org/10.37349/etat.2021.00034 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Multi-omics tumor profiling technologies to develop precision medicine in multiple myeloma, Multiple myeloma, omics data, drugs, biomarkers, predictive models, personalized medicine, Multiple myeloma (MM), the second most common hematologic cancer, is caused by accumulation of aberrant plasma cells in the bone marrow. Its molecular causes are not fully understood and its great heterogeneity among patients complicates therapeutic decision-making. In the past decades, development of new therapies and drugs have significantly improved survival of MM patients. However, resistance to drugs and relapse remain the most common causes of mortality and are the major challenges to overcome. The advent of high throughput omics technologies capable of analyzing big amount of clinical and biological data has changed the way to diagnose and treat MM. Integration of omics data (gene mutations, gene expression, epigenetic information, and protein and metabolite levels) with clinical histories of thousands of patients allows to build scores to stratify the risk at diagnosis and predict the response to treatment, helping clinicians to make better educated decisions for each particular case. There is no doubt that the future of MM treatment relies on personalized therapies based on predictive models built from omics studies. This review summarizes the current treatments and the use of omics technologies in MM, and their importance in the implementation of personalized medicine. ,Sara Ovejero, Jerome Moreaux [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [34] => Array ( [ArticleId] => 108 [Create_Time] => 2021-02-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202102/20210228095341.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100235/100235.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100235/100235.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100235/100235_cover.png [JournalsId] => 4 [Title] => Aptamers and antibodies: rivals or allies in cancer targeted therapy? [Abstract] => The goal of an efficacious cancer therapy is to specifically target diseased cells at high accuracy while sparing normal, healthy cells. Over the past three decades, immunotherapy, based on the use [AbstractComplete] =>The goal of an efficacious cancer therapy is to specifically target diseased cells at high accuracy while sparing normal, healthy cells. Over the past three decades, immunotherapy, based on the use of monoclonal antibodies (mAbs) directed against tumor-associated antigens, to inhibit their oncogenic function, or against immune checkpoints, to modulate specific T cell responses against cancer, has proven to be an important strategy for cancer therapy. Nevertheless, the number of mAbs approved for clinical use is still limited because of significant drawbacks to their applicability. Oligonucleotide aptamers, similarly to antibodies, form high-affinity bonds with their specific protein targets, thus representing an effective tool for active cancer targeting. Compared to antibodies, aptamers’ use as therapeutic agents benefits from their low size, low/no immunogenicity, simple synthesis and design flexibility for improving efficacy and stability. This review intends to highlight recently emerged applications of aptamers as recognition elements, from biomarker discovery to targeted drug delivery and targeted treatment, showing aptamers’ potential to work in conjunction with antibodies for attacking cancer from multiple flanks.
[Names] => Lisa Agnello ... Laura Cerchia [Doi] => 10.37349/etat.2021.00035 [Published] => February 28, 2021 [Viewed] => 2890 [Downloaded] => 105 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00035 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:107–121 [Recommend] => 0 [Keywords] => Aptamers, monoclonal antibodies, targeted therapy, theranostics, SELEX [DetailTitle] => [DetailUrl] => [Id] => 100235 [ris] => https://www.explorationpub.com/uploads/Article/A100235/137e518587b01ef49156fe10badd0f32.ris [bib] => https://www.explorationpub.com/uploads/Article/A100235/a4a5232d37da6f799bf6ac52f9c0989f.bib [ens] => [Cited] => 4 [Cited_Time] => 2024-04-26 [CitethisArticle] => Agnello L, Camorani S, Fedele M, Cerchia L. Aptamers and antibodies: rivals or allies in cancer targeted therapy? Explor Target Antitumor Ther. 2021;2:107-21. https://doi.org/10.37349/etat.2021.00035 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Aptamers and antibodies: rivals or allies in cancer targeted therapy?, Aptamers, monoclonal antibodies, targeted therapy, theranostics, SELEX, The goal of an efficacious cancer therapy is to specifically target diseased cells at high accuracy while sparing normal, healthy cells. Over the past three decades, immunotherapy, based on the use of monoclonal antibodies (mAbs) directed against tumor-associated antigens, to inhibit their oncogenic function, or against immune checkpoints, to modulate specific T cell responses against cancer, has proven to be an important strategy for cancer therapy. Nevertheless, the number of mAbs approved for clinical use is still limited because of significant drawbacks to their applicability. Oligonucleotide aptamers, similarly to antibodies, form high-affinity bonds with their specific protein targets, thus representing an effective tool for active cancer targeting. Compared to antibodies, aptamers’ use as therapeutic agents benefits from their low size, low/no immunogenicity, simple synthesis and design flexibility for improving efficacy and stability. This review intends to highlight recently emerged applications of aptamers as recognition elements, from biomarker discovery to targeted drug delivery and targeted treatment, showing aptamers’ potential to work in conjunction with antibodies for attacking cancer from multiple flanks. ,Lisa Agnello ... Laura Cerchia [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [35] => Array ( [ArticleId] => 115 [Create_Time] => 2021-03-09 [zipUrl] => https://www.explorationpub.com/uploads/zip/202104/20210430093912.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100236/100236.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100236/100236.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100236/100236_cover.png [JournalsId] => 4 [Title] => Potential benefit of β-glucans as adjuvant therapy in immuno-oncology: a review [Abstract] => Fungal compounds have long been used for centuries as food supplements. β-glucans have been identified as the most interesting molecules with beneficial effects in several chronic diseas [AbstractComplete] =>Fungal compounds have long been used for centuries as food supplements. β-glucans have been identified as the most interesting molecules with beneficial effects in several chronic diseases. In vitro studies have shown that they are able to elicit the immune cells maturation and activation with the result of an increased release of proinflammatory cytokines and chemokines and a stimulation of anti-bacterial activity of macrophages and neutrophils. As β-glucans enhance pathogen elimination through non-self antigens identification, they can also direct immune response against tumor cells. These compounds also stimulate the activity on adaptive immune cells and they have been regarded as biological response modifiers. In this way, β-glucans can be exploited as adjuvant cancer therapy, in particular by a synergic action with chemotherapy or immunotherapy. In the immuno-oncology era, the need is to identify innovative drugs that can simultaneously target and inhibit different biological processes relevant for cancer cells survivors. Recent clinical studies showed promising results about the combination of β-glucans and immune checkpoint inhibitors for patients affected by different solid tumors. This review aims to investigate molecular mechanisms of action of β-glucans and is focused on their application in clinical practice as immune-adjuvants for treatment of cancer patients.
[Names] => Valeria Cognigni ... Rossana Berardi [Doi] => 10.37349/etat.2021.00036 [Published] => April 30, 2021 [Viewed] => 3736 [Downloaded] => 157 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00036 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 34 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:122–138 [Recommend] => 0 [Keywords] => β-glucans, mushrooms, immuno-oncology, immune-modulating, immune checkpoint inhibitors [DetailTitle] => Immunotherapy in Cancer Patients [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/34 [Id] => 100236 [ris] => https://www.explorationpub.com/uploads/Article/A100236/a55f2f25985148ab1254272e54d0b42e.ris [bib] => https://www.explorationpub.com/uploads/Article/A100236/e44f4ed77d51cdf3c9ce5c040f8db8d8.bib [ens] => [Cited] => 4 [Cited_Time] => 2024-04-27 [CitethisArticle] => Cognigni V, Ranallo N, Tronconi F, Morgese F, Berardi R. Potential benefit of β-glucans as adjuvant therapy in immuno-oncology: a review. Explor Target Antitumor Ther. 2021;2:122-38. https://doi.org/10.37349/etat.2021.00036 [Jindex] => 0 [CName] => RossanaBerardi, [CEmail] => r.berardi@staff.univpm.it, [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Potential benefit of β-glucans as adjuvant therapy in immuno-oncology: a review, β-glucans, mushrooms, immuno-oncology, immune-modulating, immune checkpoint inhibitors, Fungal compounds have long been used for centuries as food supplements. β-glucans have been identified as the most interesting molecules with beneficial effects in several chronic diseases. In vitro studies have shown that they are able to elicit the immune cells maturation and activation with the result of an increased release of proinflammatory cytokines and chemokines and a stimulation of anti-bacterial activity of macrophages and neutrophils. As β-glucans enhance pathogen elimination through non-self antigens identification, they can also direct immune response against tumor cells. These compounds also stimulate the activity on adaptive immune cells and they have been regarded as biological response modifiers. In this way, β-glucans can be exploited as adjuvant cancer therapy, in particular by a synergic action with chemotherapy or immunotherapy. In the immuno-oncology era, the need is to identify innovative drugs that can simultaneously target and inhibit different biological processes relevant for cancer cells survivors. Recent clinical studies showed promising results about the combination of β-glucans and immune checkpoint inhibitors for patients affected by different solid tumors. This review aims to investigate molecular mechanisms of action of β-glucans and is focused on their application in clinical practice as immune-adjuvants for treatment of cancer patients. ,Valeria Cognigni ... Rossana Berardi [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [36] => Array ( [ArticleId] => 117 [Create_Time] => 2021-03-23 [zipUrl] => https://www.explorationpub.com/uploads/zip/202104/20210430095132.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100237/100237.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100237/100237.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100237/100237_cover.png [JournalsId] => 4 [Title] => Targeting HER2 in breast cancer: new drugs and paradigms on the horizon [Abstract] => About 15–20% of all breast cancers (BCs) are defined human epidermal growth factor receptor 2 (HER2)-positive, based on the overexpression of HER2 protein and/or amplification [AbstractComplete] =>About 15–20% of all breast cancers (BCs) are defined human epidermal growth factor receptor 2 (HER2)-positive, based on the overexpression of HER2 protein and/or amplification of ERBB2 gene. Such alterations lead to a more aggressive behavior of the disease, but also predict response to treatments targeting HER2. Indeed, several anti-HER2 compounds have been developed and approved in the last two decades, significantly improving our ability to cure patients in the early setting, and greatly extending their survival in the advanced setting. However, recent evolutions in this field promise to improve outcomes even further, through advancements in established HER2-targeting strategies, as well as the exploration of novel strategies. In particular, the engineering of new antibody-drug conjugates, with higher drug-to-antibody ratios (DARs) and cleavable linkers, has already led to the development of a highly effective drug, namely trastuzumab deruxtecan, recently approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of advanced HER2-positive (HER2+) BC, and currently in study in the early setting. Moreover, the novel tyrosine kinase inhibitor tucatinib was recently approved by FDA and EMA, showing to improve survival of HER2+ advanced BC patients, particularly in those with brain metastasis. Immunotherapy is also being investigated in the HER2+ subtype, through immune-checkpoint inhibition, cancer vaccines and adoptive-cell therapies. Overall, the enlarging arsenal of promising anti-HER2 compounds is expected to deliver significant improvements in the prognosis of both early and advanced HER2+ BC in the years to come. Moreover, some of such agents are showing encouraging activity in the much wider population of HER2-low advanced BC patients, challenging current BC classifications. If confirmed, this new paradigm would potentially expand the population deriving benefit from HER2-targeted treatments to up to 70% of all advanced BC patients, leading to a revolution in current treatment algorithms, and possibly to a redefinition of HER2 classification.
[Names] => Paolo Tarantino ... Giuseppe Curigliano [Doi] => 10.37349/etat.2021.00037 [Published] => April 30, 2021 [Viewed] => 4586 [Downloaded] => 201 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00037 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:139–155 [Recommend] => 0 [Keywords] => Breast cancer, HER2, antibody-drug conjugates, tyrosine-kinase inhibitors, bispecific antibodies, immunotherapy, HER2-low [DetailTitle] => [DetailUrl] => [Id] => 100237 [ris] => https://www.explorationpub.com/uploads/Article/A100237/9e489d911842ddba08a5c4e4f1810272.ris [bib] => https://www.explorationpub.com/uploads/Article/A100237/1302d992db41c7c7e9f3020444ef50ff.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-27 [CitethisArticle] => Tarantino P, Morganti S, Curigliano G. Targeting HER2 in breast cancer: new drugs and paradigms on the horizon. Explor Target Antitumor Ther. 2021;2:139-55. https://doi.org/10.37349/etat.2021.00037 [Jindex] => 0 [CName] => GiuseppeCurigliano, [CEmail] => Giuseppe.curigliano@ieo.it, [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Targeting HER2 in breast cancer: new drugs and paradigms on the horizon, Breast cancer, HER2, antibody-drug conjugates, tyrosine-kinase inhibitors, bispecific antibodies, immunotherapy, HER2-low, About 15–20% of all breast cancers (BCs) are defined human epidermal growth factor receptor 2 (HER2)-positive, based on the overexpression of HER2 protein and/or amplification of ERBB2 gene. Such alterations lead to a more aggressive behavior of the disease, but also predict response to treatments targeting HER2. Indeed, several anti-HER2 compounds have been developed and approved in the last two decades, significantly improving our ability to cure patients in the early setting, and greatly extending their survival in the advanced setting. However, recent evolutions in this field promise to improve outcomes even further, through advancements in established HER2-targeting strategies, as well as the exploration of novel strategies. In particular, the engineering of new antibody-drug conjugates, with higher drug-to-antibody ratios (DARs) and cleavable linkers, has already led to the development of a highly effective drug, namely trastuzumab deruxtecan, recently approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of advanced HER2-positive (HER2+) BC, and currently in study in the early setting. Moreover, the novel tyrosine kinase inhibitor tucatinib was recently approved by FDA and EMA, showing to improve survival of HER2+ advanced BC patients, particularly in those with brain metastasis. Immunotherapy is also being investigated in the HER2+ subtype, through immune-checkpoint inhibition, cancer vaccines and adoptive-cell therapies. Overall, the enlarging arsenal of promising anti-HER2 compounds is expected to deliver significant improvements in the prognosis of both early and advanced HER2+ BC in the years to come. Moreover, some of such agents are showing encouraging activity in the much wider population of HER2-low advanced BC patients, challenging current BC classifications. If confirmed, this new paradigm would potentially expand the population deriving benefit from HER2-targeted treatments to up to 70% of all advanced BC patients, leading to a revolution in current treatment algorithms, and possibly to a redefinition of HER2 classification. ,Paolo Tarantino ... Giuseppe Curigliano [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [37] => Array ( [ArticleId] => 119 [Create_Time] => 2021-04-13 [zipUrl] => https://www.explorationpub.com/uploads/zip/202104/20210430103602.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100238/100238.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100238/100238.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100238/100238_cover.png [JournalsId] => 4 [Title] => Liquid biopsy in NSCLC: a new challenge in radiation therapy [Abstract] => Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide. To date, tissue biopsy has been the gold standard for the diagnosis and the identification of specific mole [AbstractComplete] =>Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide. To date, tissue biopsy has been the gold standard for the diagnosis and the identification of specific molecular mutations, to guide choice of therapy. However, this procedure has several limitations. Liquid biopsy could represent a solution to the intrinsic limits of traditional biopsy. It can detect cancer markers such as circulating tumor DNA or RNA (ctDNA, ctRNA), and circulating tumor cells, in plasma, serum or other biological fluids. This procedure is minimally invasive, reproducible and can be used repeatedly. The main clinical applications of liquid biopsy in non-small cell lung cancer (NSCLC) patients are the early diagnosis, stratification of the risk of relapse, identification of mutations to guide application of targeted therapy and the evaluation of the minimum residual disease. In this review, the current role of liquid biopsy and associated markers in the management of NSCLC patients was analyzed, with emphasis on ctDNA and CTCs, and radiotherapy.
[Names] => Annarita Perillo ... Ida Rosalia Scognamiglio [Doi] => 10.37349/etat.2021.00038 [Published] => April 30, 2021 [Viewed] => 2007 [Downloaded] => 41 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00038 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 23 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:156–173 [Recommend] => 0 [Keywords] => Lung cancer, liquid biopsy, personalized therapy, radiotherapy, tissue biopsy [DetailTitle] => Liquid Biopsy in Thoracic Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/23 [Id] => 100238 [ris] => https://www.explorationpub.com/uploads/Article/A100238/81d3b126673a636d7696943aa45c3352.ris [bib] => https://www.explorationpub.com/uploads/Article/A100238/465496458a5e0c461655bdc0beee0163.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Perillo A, Agbaje Olufemi MV, De Robbio J, Mancuso RM, Roscigno A, Tirozzi M, et al. Liquid biopsy in NSCLC: a new challenge in radiation therapy. Explor Target Antitumor Ther. 2021;2:156-73. https://doi.org/10.37349/etat.2021.00038 [Jindex] => 0 [CName] => AnnaritaPerillo, [CEmail] => annaritap@live.it, [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Liquid biopsy in NSCLC: a new challenge in radiation therapy, Lung cancer, liquid biopsy, personalized therapy, radiotherapy, tissue biopsy, Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide. To date, tissue biopsy has been the gold standard for the diagnosis and the identification of specific molecular mutations, to guide choice of therapy. However, this procedure has several limitations. Liquid biopsy could represent a solution to the intrinsic limits of traditional biopsy. It can detect cancer markers such as circulating tumor DNA or RNA (ctDNA, ctRNA), and circulating tumor cells, in plasma, serum or other biological fluids. This procedure is minimally invasive, reproducible and can be used repeatedly. The main clinical applications of liquid biopsy in non-small cell lung cancer (NSCLC) patients are the early diagnosis, stratification of the risk of relapse, identification of mutations to guide application of targeted therapy and the evaluation of the minimum residual disease. In this review, the current role of liquid biopsy and associated markers in the management of NSCLC patients was analyzed, with emphasis on ctDNA and CTCs, and radiotherapy. ,Annarita Perillo ... Ida Rosalia Scognamiglio [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [38] => Array ( [ArticleId] => 120 [Create_Time] => 2021-04-13 [zipUrl] => https://www.explorationpub.com/uploads/zip/202104/20210430095544.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100239/100239.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100239/100239.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100239/100239-cover.png [JournalsId] => 4 [Title] => Gastrointestinal disorders as immune-related adverse events [Abstract] => Immune checkpoint inhibitors, such as cytotoxic T-lymphocyte antigen 4 inhibitors, programmed cell death 1 inhibitors and programmed cell death-ligand 1 inhibitors, have recently emerged as novel dr [AbstractComplete] =>Immune checkpoint inhibitors, such as cytotoxic T-lymphocyte antigen 4 inhibitors, programmed cell death 1 inhibitors and programmed cell death-ligand 1 inhibitors, have recently emerged as novel drugs in the anti-cancer therapy. Their use in different types of advanced cancer has shown good results and an increase in survival rates. However, immune-related adverse events (irAEs) are frequent and often require special care. IrAEs may affect all the organs, but they are most commonly seen in skin, lungs, endocrine glands and in the gastrointestinal tract where small bowel, colon, the liver and/or the pancreas can be involved. Despite being usually mild and self-resolving, irAEs may present in severe and life-threatening forms, causing the withdrawal of anti-cancer therapy. IrAEs, therefore, represent a challenging condition to manage that often requires the cooperation between the oncologists and the gastroenterologists in order to identify and treat them adequately.
[Names] => Daniele Balducci ... Luca Maroni [Doi] => 10.37349/etat.2021.00039 [Published] => April 30, 2021 [Viewed] => 1758 [Downloaded] => 28 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00039 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 34 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:174–186 [Recommend] => 0 [Keywords] => Cytotoxic T-lymphocyte antigen 4, programmed cell death 1, programmed cell death-ligand 1, immune checkpoint, gastrointestinal toxicity [DetailTitle] => Immunotherapy in Cancer Patients [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/34 [Id] => 100239 [ris] => https://www.explorationpub.com/uploads/Article/A100239/814b79b49715fb7a514a549770f804b2.ris [bib] => https://www.explorationpub.com/uploads/Article/A100239/c699c65640017eb61c989bd92e02fb10.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Balducci D, Quatraccioni C, Benedetti A, Marzioni M, Maroni L. Gastrointestinal disorders as immune-related adverse events. Explor Target Antitumor Ther. 2021;2:174-86. https://doi.org/10.37349/etat.2021.00039 [Jindex] => 0 [CName] => LucaMaroni, [CEmail] => l.maroni@univpm.it, [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Gastrointestinal disorders as immune-related adverse events, Cytotoxic T-lymphocyte antigen 4, programmed cell death 1, programmed cell death-ligand 1, immune checkpoint, gastrointestinal toxicity, Immune checkpoint inhibitors, such as cytotoxic T-lymphocyte antigen 4 inhibitors, programmed cell death 1 inhibitors and programmed cell death-ligand 1 inhibitors, have recently emerged as novel drugs in the anti-cancer therapy. Their use in different types of advanced cancer has shown good results and an increase in survival rates. However, immune-related adverse events (irAEs) are frequent and often require special care. IrAEs may affect all the organs, but they are most commonly seen in skin, lungs, endocrine glands and in the gastrointestinal tract where small bowel, colon, the liver and/or the pancreas can be involved. Despite being usually mild and self-resolving, irAEs may present in severe and life-threatening forms, causing the withdrawal of anti-cancer therapy. IrAEs, therefore, represent a challenging condition to manage that often requires the cooperation between the oncologists and the gastroenterologists in order to identify and treat them adequately. ,Daniele Balducci ... Luca Maroni [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [39] => Array ( [ArticleId] => 123 [Create_Time] => 2021-04-20 [zipUrl] => https://www.explorationpub.com/uploads/zip/202104/20210430095814.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100240/100240.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100240/100240.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100240/100240-cover.png [JournalsId] => 4 [Title] => Nuclear factor erythroid 2-related factor 2 modulates HER4 receptor in ovarian cancer cells to influence their sensitivity to tyrosine kinase inhibitors [Abstract] => Aim: Nuclear factor erythroid 2-related factor 2 (NRF2) is a key component in the cell’s response to oxidative and electrophilic stress and is a transcription factor regulating the expre [AbstractComplete] =>Nuclear factor erythroid 2-related factor 2 (NRF2) is a key component in the cell’s response to oxidative and electrophilic stress and is a transcription factor regulating the expression of a collection of anti-oxidative and cytoprotective genes. Human epidermal growth factor receptor 4 (HER4/erbB4) regulates growth and differentiation in many cancer types. Here, NRF2 and HER4 receptor interactions were investigated in a panel of ovarian cancer cell lines.
Pharmacological [tert-butylhydroquinone (tBHQ) and retinoid/rexinoid, bexarotene] and genetic [small interfering RNA (siRNA)] manipulations were used to activate or inhibit NRF2 function in the cell line panel (PE01, OVCAR3, SKOV3). Activity of the HER-targeted tyrosine kinase inhibitors, erlotinib (ERL) and lapatinib (LAP), was evaluated after NRF2 activation.
While tBHQ increased the levels of both phosphorylated-NRF2 (pNRF2) and HER4 in PE01, OVCAR3 and SKOV3 cells, bexatorene and NRF2-target siRNA treatment decreased pNRF2 and total HER4 levels. The tBHQ-dependent pharmacological activation of NRF2 attenuated the therapeutic effectiveness of ERL and LAP. Analyses of gene expression data from a HER4 driven reporter system and in vitro or in vivo cancer models, support NRF2 regulation of HER4 expression.
These results support the presence of signaling interaction between the NRF2 and HER4 receptor pathways and suggest that intervention modulating this cross-talk could have anticancer therapeutic value.
Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer with high heterogeneity, rapid progression, and paucity of treatment options. The most effective chemotherapeutic drug used to treat TNBC is doxorubicin (Doxo) which is an anthracycline antibiotic. However, Doxo treatment alters cytosolic calcium dynamics leading to drug-resistance condition. The aim of this study is to capture the alterations in the activity of various calcium channels and pumps during Doxo treatment and their consequences on cytosolic calcium dynamics that ultimately result in drug resistance.
In the present study, a mathematical model is proposed to capture the complex dynamical landscape of intracellular calcium during Doxo treatment. This study provides an insight into Doxo remodeling of calcium dynamics and associated drug-resistance effect. The model was first analyzed analytically and then explored through numerical simulation using techniques like global sensitivity analysis, parameter recalibration, etc.
The model is used to predict the potential combination therapy for Doxo that can overcome Doxo associated drug resistance. The results show targeting the dysregulated Ca2+ channels and pumps might provide efficient chemotherapy in TNBC. It was also observed that the indispensability of calcium influx rate is paramount in the Doxo drug resistance. Finally, three drugs were identified from existing literature that could be used as a combination therapy along with Doxo.
The investigation highlights the importance of integrating the calcium signaling of various calcium regulating compounds for their effective anti-tumor effects deliverance along with chemotherapeutic agents. The results from this study might provide a new direction to the experimental biologists to explore different combination therapies with Doxo to enhance its anti-tumor effect.
The role of tumor burden (TB) for patients with non-small cell lung cancer (NSCLC) receiving immunotherapy is still unknown. The aim of this analysis was to analyze the prognostic value of TB in a real-world sample of advanced NSCLC patients.
Sixty-five consecutive patients with advanced NSCLC treated with immunotherapy as first or second line therapy were retrospectively analyzed between August 2015 and February 2018. TB was recorded at baseline considering sites and number of metastases, thoracic vs. extrathoracic disease, measurable disease (MD) vs. not-MD (NMD) and evaluating dimensional aspects as maximum lesion diameter (cut-off = 6.3 cm), sum of the 5 major lesions diameters (cut-off = 14.3 cm), and number of sites of metastases (cut-off > 4). All cut-offs were calculated by receiver operating characteristic curves. Median overall survival (OS) was estimated using Kaplan-Meier method. A Cox regression model was carried out for univariate and multivariate analyses.
Median age was 70 years and most patients (86.2%) had a good performance status (PS-Eastern Cooperative Oncology Group < 2). No significant difference in OS was noted between subgroups of patients according to TB. Bone metastases (BM) had a negative prognostic impact [median OS (mOS), 13.8 vs. 70.0 months, P = 0.0009; median progression free survival in the second line (mPFS2) 2.97 vs. 8.63 months; P = 0.0037]. Patients with NMD had a poorer prognosis (mOS, 15.9 months vs. not reached, P < 0.0001; mPFS2 3.8 vs. 12.2 months; P = 0.0199). Patients with disease limited to the thorax had a better prognosis compared to patients with involvement of extrathoracic sites (mOS, 70 vs. 17.3 months; P = 0.0136). Having more than 4 metastatic sites resulted as a negative prognostic factor (mOS, 15.9 vs. 25.2 months; P = 0.0106). At multivariate analysis, BM, NMD, extrathoracic disease and number of sites of metastases > 4 were negative prognostic factors (P < 0.0001).
This study underlines the negative prognostic impact of specific metastatic sites, presence of NMD and extrathoracic disease in advanced NSCLC patients treated with immunotherapy. However, TB does not appear to affect the outcome of these patients.
Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline alterations in mismatch repair (MMR) genes leading to increased risk of colon cancer as well as other cancer types. Non-small cell lung cancer (NSCLC) is not among typical Lynch syndrome-associated tumors: pembrolizumab, an immune checkpoint inhibitor, is actually approved for the treatment of NSCLC patients and represents a promising treatment option for patients with advanced metastatic MMR-deficient cancer, regardless of tumor origin. This case report describes the clinical presentation and management of a 74-year-old female with a history of rectal adenocarcinoma and ovarian cancer, who has a documented frameshift pathogenic variant in the exon 8 of MSH6 gene and an intronic variant in the BRCA2 gene (classified as a variant of uncertain significance), affected by NSCLC with brain metastases. Despite these premises, the patient was treated with pembrolizumab and she did not benefit from this kind of treatment.
[Names] => Elena Maccaroni ... Rossana Berardi [Doi] => 10.37349/etat.2021.00044 [Published] => June 28, 2021 [Viewed] => 2199 [Downloaded] => 57 [Subject] => Case Report [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00044 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:240–248 [Recommend] => 0 [Keywords] => Lynch syndrome, immunotherapy, non-small cell lung cancer, microsatellite instability-high, pembrolizumab [DetailTitle] => [DetailUrl] => [Id] => 100244 [ris] => https://www.explorationpub.com/uploads/Article/A100244/3303560862687bb77fab605628d0a137.ris [bib] => https://www.explorationpub.com/uploads/Article/A100244/6008fbdd662e27d98a255c8d7d5f7191.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Maccaroni E, Lenci E, Agostinelli V, Cognigni V, Giampieri R, Mazzanti P, et al. Lynch syndrome-associated lung cancer: pitfalls of an immunotherapy-based treatment strategy in an unusual tumor type. Explor Target Antitumor Ther. 2021;2:240-8. https://doi.org/10.37349/etat.2021.00044 [Jindex] => 0 [CName] => RossanaBerardi, [CEmail] => r.berardi@univpm.it, [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Lynch syndrome-associated lung cancer: pitfalls of an immunotherapy-based treatment strategy in an unusual tumor type, Lynch syndrome, immunotherapy, non-small cell lung cancer, microsatellite instability-high, pembrolizumab, Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline alterations in mismatch repair (MMR) genes leading to increased risk of colon cancer as well as other cancer types. Non-small cell lung cancer (NSCLC) is not among typical Lynch syndrome-associated tumors: pembrolizumab, an immune checkpoint inhibitor, is actually approved for the treatment of NSCLC patients and represents a promising treatment option for patients with advanced metastatic MMR-deficient cancer, regardless of tumor origin. This case report describes the clinical presentation and management of a 74-year-old female with a history of rectal adenocarcinoma and ovarian cancer, who has a documented frameshift pathogenic variant in the exon 8 of MSH6 gene and an intronic variant in the BRCA2 gene (classified as a variant of uncertain significance), affected by NSCLC with brain metastases. Despite these premises, the patient was treated with pembrolizumab and she did not benefit from this kind of treatment. ,Elena Maccaroni ... Rossana Berardi [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [44] => Array ( [ArticleId] => 135 [Create_Time] => 2021-05-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202106/20210629025248.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100245/100245.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100245/100245.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100245/100245_cover.png [JournalsId] => 4 [Title] => Overview of Ca2+ signaling in lung cancer progression and metastatic lung cancer with bone metastasis [Abstract] => Intracellular Ca2+ ions that are thought to be one of the most important second messengers for cellular signaling, have a substantial diversity of roles in regulating a plethora of funda [AbstractComplete] =>Intracellular Ca2+ ions that are thought to be one of the most important second messengers for cellular signaling, have a substantial diversity of roles in regulating a plethora of fundamental cellular physiology such as gene expression, cell division, cell motility and apoptosis. It has been suggestive of the Ca2+ signaling-dependent cellular processes to be tightly regulated by the numerous types of Ca2+ channels, pumps, exchangers and sensing receptors. Consequently, dysregulated Ca2+ homeostasis leads to a series of events connected to elevated malignant phenotypes including uncontrolled proliferation, migration, invasion and metastasis, all of which are frequently observed in advanced stage lung cancer cells. The incidence of bone metastasis in patients with advanced stage lung cancer is estimated in a range of 30% to 40%, bringing about a significant negative impact on both morbidity and survival. This review dissects and summarizes the important roles of Ca2+ signaling transduction in contributing to lung cancer progression, and address the question: if and how Ca2+ signaling might have been engaged in metastatic lung cancer with bone metastasis, thereby potentially providing the multifaceted and promising solutions for therapeutic intervention.
[Names] => Manh Tien Tran [Doi] => 10.37349/etat.2021.00045 [Published] => June 28, 2021 [Viewed] => 2103 [Downloaded] => 50 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00045 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 35 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:249–265 [Recommend] => 0 [Keywords] => Lung cancer, Ca2+ signaling, bone metastasis, osteoclasts, bone microenvironment [DetailTitle] => Calcium Signaling Apparatus in Cancers [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/35 [Id] => 100245 [ris] => https://www.explorationpub.com/uploads/Article/A100245/a85bb546e4c58a9c3f7fe1bfc5d46790.ris [bib] => https://www.explorationpub.com/uploads/Article/A100245/31c06734c3b29f94ddcdc2176f1a1d47.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-26 [CitethisArticle] => Tran MT. Overview of Ca2+ signaling in lung cancer progression and metastatic lung cancer with bone metastasis. Explor Target Antitumor Ther. 2021;2:249-65. https://doi.org/10.37349/etat.2021.00045 [Jindex] => 0 [CName] => Manh TienTran, [CEmail] => trantienmanh1508@gmail.com, [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Overview of Ca2+ signaling in lung cancer progression and metastatic lung cancer with bone metastasis, Lung cancer, Ca2+ signaling, bone metastasis, osteoclasts, bone microenvironment, Intracellular Ca2+ ions that are thought to be one of the most important second messengers for cellular signaling, have a substantial diversity of roles in regulating a plethora of fundamental cellular physiology such as gene expression, cell division, cell motility and apoptosis. It has been suggestive of the Ca2+ signaling-dependent cellular processes to be tightly regulated by the numerous types of Ca2+ channels, pumps, exchangers and sensing receptors. Consequently, dysregulated Ca2+ homeostasis leads to a series of events connected to elevated malignant phenotypes including uncontrolled proliferation, migration, invasion and metastasis, all of which are frequently observed in advanced stage lung cancer cells. The incidence of bone metastasis in patients with advanced stage lung cancer is estimated in a range of 30% to 40%, bringing about a significant negative impact on both morbidity and survival. This review dissects and summarizes the important roles of Ca2+ signaling transduction in contributing to lung cancer progression, and address the question: if and how Ca2+ signaling might have been engaged in metastatic lung cancer with bone metastasis, thereby potentially providing the multifaceted and promising solutions for therapeutic intervention. ,Manh Tien Tran [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [45] => Array ( [ArticleId] => 138 [Create_Time] => 2021-06-21 [zipUrl] => https://www.explorationpub.com/uploads/zip/202106/20210629025414.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100246/100246.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100246/100246.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100246/100246_cover.png [JournalsId] => 4 [Title] => Advances in the study of cancer metastasis and calcium signaling as potential therapeutic targets [Abstract] => Metastasis is still the primary cause of cancer-related mortality. However, the underlying mechanisms of cancer metastasis are not yet fully understood. Currently, the epithelial-mesenchymal transit [AbstractComplete] =>Metastasis is still the primary cause of cancer-related mortality. However, the underlying mechanisms of cancer metastasis are not yet fully understood. Currently, the epithelial-mesenchymal transition, metabolic remodeling, cancer cell intercommunication and the tumor microenvironment including diverse stromal cells, are reported to affect the metastatic process of cancer cells. Calcium ions (Ca2+) are ubiquitous second messengers that manipulate cancer metastasis by affecting signaling pathways. Diverse transporter/pump/channel-mediated Ca2+ currents form Ca2+ oscillations that can be decoded by Ca2+-binding proteins, which are promising prognostic biomarkers and therapeutic targets of cancer metastasis. This paper presents a review of the advances in research on the mechanisms underlying cancer metastasis and the roles of Ca2+-related signals in these events.
[Names] => Chaochu Cui ... Xianwei Wang [Doi] => 10.37349/etat.2021.00046 [Published] => June 28, 2021 [Viewed] => 2612 [Downloaded] => 124 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00046 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 35 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:266–291 [Recommend] => 0 [Keywords] => Calcium channel, cancer metastasis, epithelial-mesenchymal transition, tumor microenvironment, immunosurveillance, metastatic colonization [DetailTitle] => Calcium Signaling Apparatus in Cancers [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/35 [Id] => 100246 [ris] => https://www.explorationpub.com/uploads/Article/A100246/63598b5120246879d09ceafcda7b8b08.ris [bib] => https://www.explorationpub.com/uploads/Article/A100246/ec271a9f22d76ad82edae410ee56b59e.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Cui CC, Zhang YX, Liu G, Zhang SH, Zhang JH, Wang XW. Advances in the study of cancer metastasis and calcium signaling as potential therapeutic targets. Explor Target Antitumor Ther. 2021;2:266-91. https://doi.org/10.37349/etat.2021.00046 [Jindex] => 0 [CName] => XianweiWang, [CEmail] => Wangxianwei1116@126.com, [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Advances in the study of cancer metastasis and calcium signaling as potential therapeutic targets, Calcium channel, cancer metastasis, epithelial-mesenchymal transition, tumor microenvironment, immunosurveillance, metastatic colonization, Metastasis is still the primary cause of cancer-related mortality. However, the underlying mechanisms of cancer metastasis are not yet fully understood. Currently, the epithelial-mesenchymal transition, metabolic remodeling, cancer cell intercommunication and the tumor microenvironment including diverse stromal cells, are reported to affect the metastatic process of cancer cells. Calcium ions (Ca2+) are ubiquitous second messengers that manipulate cancer metastasis by affecting signaling pathways. Diverse transporter/pump/channel-mediated Ca2+ currents form Ca2+ oscillations that can be decoded by Ca2+-binding proteins, which are promising prognostic biomarkers and therapeutic targets of cancer metastasis. This paper presents a review of the advances in research on the mechanisms underlying cancer metastasis and the roles of Ca2+-related signals in these events. ,Chaochu Cui ... Xianwei Wang [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [46] => Array ( [ArticleId] => 140 [Create_Time] => 2021-06-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202106/20210629050514.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100247/100247.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100247/100247.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100247/100247_cover.png [JournalsId] => 4 [Title] => Targeting cytoskeletal phosphorylation in cancer [Abstract] => Phosphorylation of cytoskeletal proteins regulates the dynamics of polymerization, stability, and disassembly of the different types of cytoskeletal polymers. These control the ability of cells to m [AbstractComplete] =>Phosphorylation of cytoskeletal proteins regulates the dynamics of polymerization, stability, and disassembly of the different types of cytoskeletal polymers. These control the ability of cells to migrate and divide. Mutations and alterations of the expression levels of multiple protein kinases are hallmarks of most forms of cancer. Thus, altered phosphorylation of cytoskeletal proteins is observed in most cancer cells. These alterations potentially control the ability of cancer cells to divide, invade and form distal metastasis. This review highlights the emergent role of phosphorylation in the control of the function of the different cytoskeletal polymers in cancer cells. It also addresses the potential effect of targeted inhibitors in the normalization of cytoskeletal function.
[Names] => Clara Llorente-González ... Miguel Vicente-Manzanares [Doi] => 10.37349/etat.2021.00047 [Published] => June 28, 2021 [Viewed] => 1716 [Downloaded] => 69 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00047 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:292–308 [Recommend] => 0 [Keywords] => Cytoskeleton, phosphorylation, cancer, actin, tubulin, vimentin, myosin [DetailTitle] => [DetailUrl] => [Id] => 100247 [ris] => https://www.explorationpub.com/uploads/Article/A100247/035dfc6a6025524e0d9f46224df4a62a.ris [bib] => https://www.explorationpub.com/uploads/Article/A100247/82f319943877315efd8a3aa3ae1f5218.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Llorente-González C, González-Rodríguez M, Vicente-Manzanares M. Targeting cytoskeletal phosphorylation in cancer. Explor Target Antitumor Ther. 2021;2:292-308. https://doi.org/10.37349/etat.2021.00047 [Jindex] => 0 [CName] => MiguelVicente-Manzanares, [CEmail] => miguel.vicente@csic.es, [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Targeting cytoskeletal phosphorylation in cancer, Cytoskeleton, phosphorylation, cancer, actin, tubulin, vimentin, myosin, Phosphorylation of cytoskeletal proteins regulates the dynamics of polymerization, stability, and disassembly of the different types of cytoskeletal polymers. These control the ability of cells to migrate and divide. Mutations and alterations of the expression levels of multiple protein kinases are hallmarks of most forms of cancer. Thus, altered phosphorylation of cytoskeletal proteins is observed in most cancer cells. These alterations potentially control the ability of cancer cells to divide, invade and form distal metastasis. This review highlights the emergent role of phosphorylation in the control of the function of the different cytoskeletal polymers in cancer cells. It also addresses the potential effect of targeted inhibitors in the normalization of cytoskeletal function. ,Clara Llorente-González ... Miguel Vicente-Manzanares [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [47] => Array ( [ArticleId] => 159 [Create_Time] => 2021-08-11 [zipUrl] => https://www.explorationpub.com/uploads/zip/202108/20210831032142.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100248/100248.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100248/100248.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100248/100248-cover.png [JournalsId] => 4 [Title] => The effect of iron on the expression levels of calcium related gene in cisplatin resistant epithelial ovarian cancer cells [Abstract] => Aim: Anticancer drugs (chemotherapeutics) used in cancer treatment (chemotherapy) lead to drug resistance. This study was conducted to investigate the possible effect of iron on calcium homeostasis [AbstractComplete] =>Anticancer drugs (chemotherapeutics) used in cancer treatment (chemotherapy) lead to drug resistance. This study was conducted to investigate the possible effect of iron on calcium homeostasis in epithelial ovarian cancer cells (MDAH-2774) and cisplatin-resistant cells of the same cell line (MDAH-2774/DDP).
To develop MDAH-2774/DDP cells, MDAH-2774 (MDAH) cells were treated with cisplatin in dose increases of 5 μM between 0 μM and 70 μM. The effect of iron on the viability of MDAH and MDAH/DDP cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test at the end of 24 h incubation.
At increasing iron concentrations in MDAH and MDAH/DDP cells, the mRNA gene of fifteen genes [inositol 1,4,5-triphosphate receptor (IP3R)1/2/3, ryanodine receptor (RYR)1/2, sarco/endoplasmic reticulum Ca2+ ATPase (SERCA)1/2/3, Na+/Ca2+ exchange (NCX)1/2/3, and plasma membrane Ca2+ ATPase (PMCA)1/2/3/4] associated with Ca2+ differences in expression were determined by quantitative reverse transcription-polymerase chain reaction. Changes in IP3R2, RYR1, SERCA2, NCX3, PMCA1, and PMCA3 gene expressions were observed in iron treatment of MDAH/DDP cells, while changes were detected in iron treatment of MDAH cells in IP3R1/2/3, RYR1/2, SERCA1/2/3, NCX2/3, and PMCA1 expressions.
This changes in the expression of calcium channels, pumps, and exchange proteins in the epithelial ovarian cancer cell line and in cisplatin-resistant epithelial ovarian cancer cells suggest that iron may have an important role in regulating calcium homeostasis. Due to differences in the expression of genes that play of an important role in the regulation of calcium homeostasis in the effect of iron, drug resistance can be prevented by introducing a new perspective on the use of inhibitors and activators of these genes and thus cytostatic treatment strategies.
In spite of the immense advancement in the diagnostic and treatment modalities, cancer continues to be one of the leading causes of mortality across the globe, responsible for the death of around 10 million patients every year. The foremost challenges faced in the treatment of this disease are chemoresistance, adverse effects of the drugs, and the high cost of treatment. Though scientific studies over the past few decades have foreseen and are focusing on the cancer-preventive and therapeutic potential of natural products and their underlying mechanism of action, many more of these agents are not still explored. Piperlongumine (PL), or piplartine, is one such alkaloid isolated from Piper longum Linn., which is shown to be safe and has significant potential in the prevention and therapy of cancer. Numerous shreds of evidence have established the ability of this alkaloid and its analogs and nanoformulations in modulating various complex molecular pathways such as phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin, nuclear factor-kappa B, Janus kinases/signal transducer and activator of transcription 3, etc. and inhibit different hallmarks of cancer such as cell survival, proliferation, invasion, angiogenesis, epithelial-mesenchymal-transition, metastases, etc. In addition, PL was also shown to inhibit radioresistance and chemoresistance and sensitize the cancer cells to the standard chemotherapeutic agents. Therefore, this compound has high potential as a drug candidate for the prevention and treatment of different cancers. The current review briefly reiterates the anti-cancer properties of PL against different types of cancer, which permits further investigation by conducting clinical studies.
[Names] => Dey Parama ... Ajaikumar B. Kunnumakkara [Doi] => 10.37349/etat.2021.00049 [Published] => August 30, 2021 [Viewed] => 3909 [Downloaded] => 152 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00049 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:323–354 [Recommend] => 0 [Keywords] => Piperlongumine, piplartine, Piper longum Linn., cancer, signaling pathways, chemotherapy, radiotherapy, toxicity [DetailTitle] => [DetailUrl] => [Id] => 100249 [ris] => https://www.explorationpub.com/uploads/Article/A100249/62c1d90034264dc79d13c33422563574.ris [bib] => https://www.explorationpub.com/uploads/Article/A100249/a21271a73d5e96a857d7cdd36bd04f38.bib [ens] => [Cited] => 6 [Cited_Time] => 2024-04-27 [CitethisArticle] => Parama D, Rana V, Girisa S, Verma E, Daimary UD, Thakur KK, et al. The promising potential of piperlongumine as an emerging therapeutics for cancer. Explor Target Antitumor Ther. 2021;2:323-54. https://doi.org/10.37349/etat.2021.00049 [Jindex] => 0 [CName] => Ajaikumar B.Kunnumakkara, [CEmail] => kunnumakkara@iitg.ac.in, [Ris_Time] => 2021-09-03 09:02:24 [Bib_Time] => 2021-09-03 09:02:24 [KeysWordContens] => The promising potential of piperlongumine as an emerging therapeutics for cancer, Piperlongumine, piplartine, Piper longum Linn., cancer, signaling pathways, chemotherapy, radiotherapy, toxicity, In spite of the immense advancement in the diagnostic and treatment modalities, cancer continues to be one of the leading causes of mortality across the globe, responsible for the death of around 10 million patients every year. The foremost challenges faced in the treatment of this disease are chemoresistance, adverse effects of the drugs, and the high cost of treatment. Though scientific studies over the past few decades have foreseen and are focusing on the cancer-preventive and therapeutic potential of natural products and their underlying mechanism of action, many more of these agents are not still explored. Piperlongumine (PL), or piplartine, is one such alkaloid isolated from Piper longum Linn., which is shown to be safe and has significant potential in the prevention and therapy of cancer. Numerous shreds of evidence have established the ability of this alkaloid and its analogs and nanoformulations in modulating various complex molecular pathways such as phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin, nuclear factor-kappa B, Janus kinases/signal transducer and activator of transcription 3, etc. and inhibit different hallmarks of cancer such as cell survival, proliferation, invasion, angiogenesis, epithelial-mesenchymal-transition, metastases, etc. In addition, PL was also shown to inhibit radioresistance and chemoresistance and sensitize the cancer cells to the standard chemotherapeutic agents. Therefore, this compound has high potential as a drug candidate for the prevention and treatment of different cancers. The current review briefly reiterates the anti-cancer properties of PL against different types of cancer, which permits further investigation by conducting clinical studies. ,Dey Parama ... Ajaikumar B. Kunnumakkara [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [49] => Array ( [ArticleId] => 164 [Create_Time] => 2021-08-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202109/20210903071400.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100250/100250.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100250/100250.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100250/100250-cover.png [JournalsId] => 4 [Title] => The evolving role and utility of off-label drug use in multiple myeloma [Abstract] => The treatment landscape for multiple myeloma (MM) has dramatically changed over the last three decades, moving from no US Food and Drug Administration approvals and two active drug classes to over 1 [AbstractComplete] =>The treatment landscape for multiple myeloma (MM) has dramatically changed over the last three decades, moving from no US Food and Drug Administration approvals and two active drug classes to over 19 drug approvals and at least eight different active classes. The advances seen in MM therapy have relied on both a structured approach to obtaining new labels and cautious off-label drug use. Although there are country and regional differences in drug approval processes, many of the basic principles behind off-label drug use in MM can be summarized into four main categories: 1) use of a therapy prior to the current approval regulations; 2) widespread use of a therapy following the release of promising clinical trial results but prior to drug approval; 3) use of a cheap therapy supported by clinical safety and efficacy data but without commercial backing; and 4) niche therapies for small well-defined patient populations where large clinical trials with sufficient power may be difficult to perform. This review takes a historical approach to discuss how off-label drug use has helped to shape the current treatment approach for MM.
[Names] => James H Stoeckle ... Gareth J Morgan [Doi] => 10.37349/etat.2021.00050 [Published] => August 30, 2021 [Viewed] => 3010 [Downloaded] => 43 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00050 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 32 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:355–373 [Recommend] => 0 [Keywords] => Multiple myeloma, off-label, drug development, orphan drugs, thalidomide, relapsed refractory [DetailTitle] => Off-Label Drugs and -Omics Data in Cancer Treatment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/32 [Id] => 100250 [ris] => https://www.explorationpub.com/uploads/Article/A100250/567e949eda2027478cdde52f0df129cf.ris [bib] => https://www.explorationpub.com/uploads/Article/A100250/c29bad881854d377ba4d57a4e4cfacb8.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Stoeckle JH, Davies FE, Williams L, Boyle EM, Morgan GJ. The evolving role and utility of off-label drug use in multiple myeloma. Explor Target Antitumor Ther. 2021;2:355-73. https://doi.org/10.37349/etat.2021.00050 [Jindex] => 0 [CName] => Gareth JMorgan, [CEmail] => gareth.morgan@nyulangone.org, [Ris_Time] => 2021-09-03 07:14:01 [Bib_Time] => 2021-09-03 07:14:01 [KeysWordContens] => The evolving role and utility of off-label drug use in multiple myeloma, Multiple myeloma, off-label, drug development, orphan drugs, thalidomide, relapsed refractory, The treatment landscape for multiple myeloma (MM) has dramatically changed over the last three decades, moving from no US Food and Drug Administration approvals and two active drug classes to over 19 drug approvals and at least eight different active classes. The advances seen in MM therapy have relied on both a structured approach to obtaining new labels and cautious off-label drug use. Although there are country and regional differences in drug approval processes, many of the basic principles behind off-label drug use in MM can be summarized into four main categories: 1) use of a therapy prior to the current approval regulations; 2) widespread use of a therapy following the release of promising clinical trial results but prior to drug approval; 3) use of a cheap therapy supported by clinical safety and efficacy data but without commercial backing; and 4) niche therapies for small well-defined patient populations where large clinical trials with sufficient power may be difficult to perform. This review takes a historical approach to discuss how off-label drug use has helped to shape the current treatment approach for MM. ,James H Stoeckle ... Gareth J Morgan [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [50] => Array ( [ArticleId] => 165 [Create_Time] => 2021-08-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202109/20210903072651.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100251/100251.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100251/100251.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100251/100251_cover.png [JournalsId] => 4 [Title] => Does the gut microbiome environment influence response to systemic breast cancer treatment? [Abstract] => The gut microbiome is a novel player in the pathogenesis and treatment of breast cancer. The term “microbiome” is used to describe the diverse community of micro-organisms exis [AbstractComplete] =>The gut microbiome is a novel player in the pathogenesis and treatment of breast cancer. The term “microbiome” is used to describe the diverse community of micro-organisms existing within the gastrointestinal tract. The gut microbiome plays an important role in oestrogen metabolism through its ability to deconjugate oestrogens within the gut resulting in their reabsorption. Therefore, it is not unsurprising that “dysbiosis”, the disruption of normal gut microbiota composition, is now thought to play a role in the development of the disease, as women with breast cancer have been shown to have altered gut microbiota and this has been correlated with tumour characteristics. There is emerging evidence to suggest that the gut microbiota may also impact on breast cancer treatment, by mediating both drug efficacy and toxicity. The present review will discuss the influence of the gut microbiota on systemic treatments for breast cancer, including chemotherapy, anti-human epidermal growth factor receptor 2 (HER2) therapy, endocrine therapy and immunotherapy as well as other targeted treatments.
[Names] => Eilidh Bruce ... Beatrix Elsberger [Doi] => 10.37349/etat.2021.00051 [Published] => August 30, 2021 [Viewed] => 1913 [Downloaded] => 55 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00051 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:374–384 [Recommend] => 0 [Keywords] => Breast cancer, gut microbiome, gut microbiota, dysbiosis, estrobolome [DetailTitle] => [DetailUrl] => [Id] => 100251 [ris] => https://www.explorationpub.com/uploads/Article/A100251/adc33d09a7265cd824d1ccd0224f359d.ris [bib] => https://www.explorationpub.com/uploads/Article/A100251/800202b7c5a8ffd79f30e5c287342bf0.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Bruce E, Makaranka S, Urquhart G, Elsberger B. Does the gut microbiome environment influence response to systemic breast cancer treatment? Explor Target Antitumor Ther. 2021;2:374-84. https://doi.org/10.37349/etat.2021.00051 [Jindex] => 0 [CName] => BeatrixElsberger, [CEmail] => Beatrix.elsberger@nhs.scot, [Ris_Time] => 2021-09-03 06:47:00 [Bib_Time] => 2021-09-03 06:47:00 [KeysWordContens] => Does the gut microbiome environment influence response to systemic breast cancer treatment?, Breast cancer, gut microbiome, gut microbiota, dysbiosis, estrobolome, The gut microbiome is a novel player in the pathogenesis and treatment of breast cancer. The term “microbiome” is used to describe the diverse community of micro-organisms existing within the gastrointestinal tract. The gut microbiome plays an important role in oestrogen metabolism through its ability to deconjugate oestrogens within the gut resulting in their reabsorption. Therefore, it is not unsurprising that “dysbiosis”, the disruption of normal gut microbiota composition, is now thought to play a role in the development of the disease, as women with breast cancer have been shown to have altered gut microbiota and this has been correlated with tumour characteristics. There is emerging evidence to suggest that the gut microbiota may also impact on breast cancer treatment, by mediating both drug efficacy and toxicity. The present review will discuss the influence of the gut microbiota on systemic treatments for breast cancer, including chemotherapy, anti-human epidermal growth factor receptor 2 (HER2) therapy, endocrine therapy and immunotherapy as well as other targeted treatments. ,Eilidh Bruce ... Beatrix Elsberger [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [51] => Array ( [ArticleId] => 166 [Create_Time] => 2021-08-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202109/20210903085005.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100252/100252.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100252/100252.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100252/100252_cover.png [JournalsId] => 4 [Title] => Role of estrogen receptor coregulators in endocrine resistant breast cancer [Abstract] => Breast cancer (BC) is the most ubiquitous cancer in women. Approximately 70–80% of BC diagnoses are positive for estrogen receptor (ER) alpha (ERα). The steroid ho [AbstractComplete] =>Breast cancer (BC) is the most ubiquitous cancer in women. Approximately 70–80% of BC diagnoses are positive for estrogen receptor (ER) alpha (ERα). The steroid hormone estrogen [17β-estradiol (E2)] plays a vital role both in the initiation and progression of BC. The E2-ERα mediated actions involve genomic signaling and non-genomic signaling. The specificity and magnitude of ERα signaling are mediated by interactions between ERα and several coregulator proteins called coactivators or corepressors. Alterations in the levels of coregulators are common during BC progression and they enhance ligand-dependent and ligand-independent ERα signaling which drives BC growth, progression, and endocrine therapy resistance. Many ERα coregulator proteins function as scaffolding proteins and some have intrinsic or associated enzymatic activities, thus the targeting of coregulators for blocking BC progression is a challenging task. Emerging data from in vitro and in vivo studies suggest that targeting coregulators to inhibit BC progression to therapy resistance is feasible. This review explores the current state of ERα coregulator signaling and the utility of targeting the ERα coregulator axis in treating advanced BC.
[Names] => Kristin A. Altwegg, Ratna K. Vadlamudi [Doi] => 10.37349/etat.2021.00052 [Published] => August 30, 2021 [Viewed] => 3108 [Downloaded] => 97 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00052 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 48 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:385–400 [Recommend] => 0 [Keywords] => Estrogen receptor, coregulators, transcriptional activation, estrogen, hormonal action, signal transduction, endocrine therapy resistance [DetailTitle] => Endocrine Resistant Breast Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/48 [Id] => 100252 [ris] => https://www.explorationpub.com/uploads/Article/A100252/fb536a19da572f6af11dfbae9ebf9c3e.ris [bib] => https://www.explorationpub.com/uploads/Article/A100252/999511617d8d19de4c987c795fba3d65.bib [ens] => [Cited] => 7 [Cited_Time] => 2024-04-27 [CitethisArticle] => Altwegg KA, Vadlamudi RK. Role of estrogen receptor coregulators in endocrine resistant breast cancer. Explor Target Antitumor Ther. 2021;2:385-400. https://doi.org/10.37349/etat.2021.00052 [Jindex] => 0 [CName] => Ratna K.Vadlamudi, [CEmail] => vadlamudi@uthscsa.edu, [Ris_Time] => 0000-00-00 00:00:00 [Bib_Time] => 0000-00-00 00:00:00 [KeysWordContens] => Role of estrogen receptor coregulators in endocrine resistant breast cancer, Estrogen receptor, coregulators, transcriptional activation, estrogen, hormonal action, signal transduction, endocrine therapy resistance, Breast cancer (BC) is the most ubiquitous cancer in women. Approximately 70–80% of BC diagnoses are positive for estrogen receptor (ER) alpha (ERα). The steroid hormone estrogen [17β-estradiol (E2)] plays a vital role both in the initiation and progression of BC. The E2-ERα mediated actions involve genomic signaling and non-genomic signaling. The specificity and magnitude of ERα signaling are mediated by interactions between ERα and several coregulator proteins called coactivators or corepressors. Alterations in the levels of coregulators are common during BC progression and they enhance ligand-dependent and ligand-independent ERα signaling which drives BC growth, progression, and endocrine therapy resistance. Many ERα coregulator proteins function as scaffolding proteins and some have intrinsic or associated enzymatic activities, thus the targeting of coregulators for blocking BC progression is a challenging task. Emerging data from in vitro and in vivo studies suggest that targeting coregulators to inhibit BC progression to therapy resistance is feasible. This review explores the current state of ERα coregulator signaling and the utility of targeting the ERα coregulator axis in treating advanced BC. ,Kristin A. Altwegg, Ratna K. Vadlamudi [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [52] => Array ( [ArticleId] => 176 [Create_Time] => 2021-09-26 [zipUrl] => https://www.explorationpub.com/uploads/zip/202111/20211108093941.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100253/100253.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100253/100253.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100253/100253-cover.png [JournalsId] => 4 [Title] => A novel strategy for treating cancer: understanding the role of Ca2+ signaling from nociceptive TRP channels in regulating cancer progression [Abstract] => Cancer is an aging-associated disease and caused by genomic instability that is driven by the accumulation of mutations and epimutations in the aging process. Although Ca2+ signaling, re [AbstractComplete] =>Cancer is an aging-associated disease and caused by genomic instability that is driven by the accumulation of mutations and epimutations in the aging process. Although Ca2+ signaling, reactive oxygen species (ROS) accumulation, DNA damage response (DDR) and senescence inflammation response (SIR) are processed during genomic instability, the underlying mechanism for the cause of genomic instability and cancer development is still poorly understood and needs to be investigated. Nociceptive transient receptor potential (TRP) channels, which firstly respond to environmental stimuli, such as microbes, chemicals or physical injuries, potentiate regulation of the aging process by Ca2+ signaling. In this review, the authors provide an explanation of the dual role of nociceptive TRP channels in regulating cancer progression, initiating cancer progression by aging-induced genomic instability, and promoting malignancy by epigenetic regulation. Thus, therapeutically targeting nociceptive TRP channels seems to be a novel strategy for treating cancers.
[Names] => Wen-Li Hsu ... Etsuro Ito [Doi] => 10.37349/etat.2021.00053 [Published] => October 31, 2021 [Viewed] => 2102 [Downloaded] => 67 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00053 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 35 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:401–415 [Recommend] => 0 [Keywords] => Aging, nociceptive transient receptor potential channel, cancer progression [DetailTitle] => Calcium Signaling Apparatus in Cancers [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/35 [Id] => 100253 [ris] => https://www.explorationpub.com/uploads/Article/A100253/7646eda8018021ab59c1d8bd3b34096c.ris [bib] => https://www.explorationpub.com/uploads/Article/A100253/95976cdc16f229a7e1d684ab0963a7b8.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Hsu WL, Noda M, Yoshioka T, Ito E. A novel strategy for treating cancer: understanding the role of Ca2+ signaling from nociceptive TRP channels in regulating cancer progression. Explor Target Antitumor Ther. 2021;2:401-15. https://doi.org/10.37349/etat.2021.00053 [Jindex] => 0 [CName] => EtsuroIto, [CEmail] => eito@waseda.jp, [Ris_Time] => 2021-11-02 01:44:31 [Bib_Time] => 2021-11-02 01:44:31 [KeysWordContens] => A novel strategy for treating cancer: understanding the role of Ca2+ signaling from nociceptive TRP channels in regulating cancer progression, Aging, nociceptive transient receptor potential channel, cancer progression, Cancer is an aging-associated disease and caused by genomic instability that is driven by the accumulation of mutations and epimutations in the aging process. Although Ca2+ signaling, reactive oxygen species (ROS) accumulation, DNA damage response (DDR) and senescence inflammation response (SIR) are processed during genomic instability, the underlying mechanism for the cause of genomic instability and cancer development is still poorly understood and needs to be investigated. Nociceptive transient receptor potential (TRP) channels, which firstly respond to environmental stimuli, such as microbes, chemicals or physical injuries, potentiate regulation of the aging process by Ca2+ signaling. In this review, the authors provide an explanation of the dual role of nociceptive TRP channels in regulating cancer progression, initiating cancer progression by aging-induced genomic instability, and promoting malignancy by epigenetic regulation. Thus, therapeutically targeting nociceptive TRP channels seems to be a novel strategy for treating cancers. ,Wen-Li Hsu ... Etsuro Ito [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [53] => Array ( [ArticleId] => 186 [Create_Time] => 2021-10-09 [zipUrl] => https://www.explorationpub.com/uploads/zip/202111/20211101040638.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100254/100254.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100254/100254.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100254/100254_cover.png [JournalsId] => 4 [Title] => Current options and future directions of systemic therapy for advanced biliary tract cancer [Abstract] => Biliary tract cancers (BTCs) are aggressive tumors arising from different portions of the biliary tree and classified according to the anatomical location in intrahepatic (i) cholangiocarcinoma (CCA [AbstractComplete] =>Biliary tract cancers (BTCs) are aggressive tumors arising from different portions of the biliary tree and classified according to the anatomical location in intrahepatic (i) cholangiocarcinoma (CCA, iCCA), perihilar CCA (pCCA), and distal CCA (dCCA), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). Due to their silent behavior, BTCs are frequently diagnosed at advanced stages when the prognosis is poor. The available chemotherapeutic options are palliative and unfortunately, most patients will die from their disease between 6 and 18 months from diagnosis. However, over the last decade, amounting interest has been posed on the genomic landscape of BTCs and deep-sequencing studies have identified different potentially actionable driver mutations. Hence, the promising results of the early phase clinical studies with targeted agents against isocitrate dehydrogenase (IDH) 1 mutation or fibroblast growth factor (FGF) receptor (FGFR) 2 aberrations inintrahepatic tumors, and other agents against humanepidermal growth factor receptor (HER) 2 overexpression/mutations, neurotrophic tyrosine receptor kinase (NTRK) fusions or B-type Raf kinase (BRAF) mutations across different subtypes of BTCs, have paved the way for a “precision medicine” strategy for BTCs. Moreover, despite the modest results when used as monotherapy, beyond microsatellite instability-high (MSI-H) tumors, immune checkpoint inhibitors are being evaluated in combination with platinum-based chemotherapy, possibly further expanding the therapeutic landscape of advanced BTCs. This review aims to provide an overview of the approved systemic therapies, the promising results, and the ongoing studies to explore the current and future directions of advanced BTC systemic treatment.
[Names] => Maria Giuseppina Prete ... Lorenza Rimassa [Doi] => 10.37349/etat.2021.00054 [Published] => October 31, 2021 [Viewed] => 2761 [Downloaded] => 79 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00054 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 41 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:416–433 [Recommend] => 0 [Keywords] => Biliary tract cancer, cholangiocarcinoma, chemotherapy, molecular profiling, driver mutations, targeted therapy, immunotherapy [DetailTitle] => Precision Medicine for Cholangiocarcinoma [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/41 [Id] => 100254 [ris] => https://www.explorationpub.com/uploads/Article/A100254/79594ee7602b3fe71632eba204565e65.ris [bib] => https://www.explorationpub.com/uploads/Article/A100254/2ccbbd1ce60fb8b6e78896b59d017820.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Prete MG, Cammarota A, D’Alessio A, Zanuso V, Rimassa L. Current options and future directions of systemic therapy for advanced biliary tract cancer. Explor Target Antitumor Ther. 2021;2:416-33. https://doi.org/10.37349/etat.2021.00054 [Jindex] => 0 [CName] => LorenzaRimassa, [CEmail] => lorenza.rimassa@hunimed.eu, [Ris_Time] => 2021-11-01 03:41:33 [Bib_Time] => 2021-11-01 03:41:33 [KeysWordContens] => Current options and future directions of systemic therapy for advanced biliary tract cancer, Biliary tract cancer, cholangiocarcinoma, chemotherapy, molecular profiling, driver mutations, targeted therapy, immunotherapy, Biliary tract cancers (BTCs) are aggressive tumors arising from different portions of the biliary tree and classified according to the anatomical location in intrahepatic (i) cholangiocarcinoma (CCA, iCCA), perihilar CCA (pCCA), and distal CCA (dCCA), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). Due to their silent behavior, BTCs are frequently diagnosed at advanced stages when the prognosis is poor. The available chemotherapeutic options are palliative and unfortunately, most patients will die from their disease between 6 and 18 months from diagnosis. However, over the last decade, amounting interest has been posed on the genomic landscape of BTCs and deep-sequencing studies have identified different potentially actionable driver mutations. Hence, the promising results of the early phase clinical studies with targeted agents against isocitrate dehydrogenase (IDH) 1 mutation or fibroblast growth factor (FGF) receptor (FGFR) 2 aberrations inintrahepatic tumors, and other agents against humanepidermal growth factor receptor (HER) 2 overexpression/mutations, neurotrophic tyrosine receptor kinase (NTRK) fusions or B-type Raf kinase (BRAF) mutations across different subtypes of BTCs, have paved the way for a “precision medicine” strategy for BTCs. Moreover, despite the modest results when used as monotherapy, beyond microsatellite instability-high (MSI-H) tumors, immune checkpoint inhibitors are being evaluated in combination with platinum-based chemotherapy, possibly further expanding the therapeutic landscape of advanced BTCs. This review aims to provide an overview of the approved systemic therapies, the promising results, and the ongoing studies to explore the current and future directions of advanced BTC systemic treatment. ,Maria Giuseppina Prete ... Lorenza Rimassa [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [54] => Array ( [ArticleId] => 187 [Create_Time] => 2021-10-09 [zipUrl] => https://www.explorationpub.com/uploads/zip/202111/20211101033427.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100255/100255.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100255/100255.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100255/100255_cover.png [JournalsId] => 4 [Title] => Targeting protein kinase CK2 in the treatment of cholangiocarcinoma [Abstract] => Cholangiocarcinoma (CCA) is a disease with a very poor prognosis and limited treatment options. Although targeted therapies directed towards specific mutations found in CCA are becoming available an [AbstractComplete] =>Cholangiocarcinoma (CCA) is a disease with a very poor prognosis and limited treatment options. Although targeted therapies directed towards specific mutations found in CCA are becoming available and are showing great potential, many tumors do not carry actionable mutations and, in those that do, the emergence of drug resistance is a likely consequence of treatment. Therapeutic targeting of enzymes and other proteins that show elevated activity in CCA cells but which are not altered by mutation is a potential strategy for the treatment of target negative and drug-resistant disease. Protein kinase CK2 (CK2) is a ubiquitously expressed kinase that has increased expression and increased activity in a variety of cancer types including CCA. Several potent CK2 inhibitors are in pre-clinical development or under assessment in a variety of clinical trials often in combination with drugs that induce DNA damage. This review outlines the importance of CK2 in CCA and assesses the progress that has been made in the evaluation of CK2 inhibition as a treatment strategy in this disease. Targeting CK2 based on the expression levels or activity of this protein and/or in combination with drugs that induce DNA damage or inhibit cell cycle progression, could be a viable option for tumors that lack actionable mutations, or for tumors that develop resistance to targeted treatments.
[Names] => Padma-Sheela Jayaraman, Kevin Gaston [Doi] => 10.37349/etat.2021.00055 [Published] => October 31, 2021 [Viewed] => 1974 [Downloaded] => 65 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00055 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 41 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:434–447 [Recommend] => 0 [Keywords] => Cholangiocarcinoma, protein kinase CK2, casein kinase II, dose-dependent synthetic lethality, DNA damage response, apoptosis, methuosis [DetailTitle] => Precision Medicine for Cholangiocarcinoma [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/41 [Id] => 100255 [ris] => https://www.explorationpub.com/uploads/Article/A100255/3cfc8ed3f9c311c5deca88dceab17771.ris [bib] => https://www.explorationpub.com/uploads/Article/A100255/442663d2d07502862c15cfa957dc5e48.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Jayaraman PS, Gaston K. Targeting protein kinase CK2 in the treatment of cholangiocarcinoma. Explor Target Antitumor Ther. 2021;2:434-47. https://doi.org/10.37349/etat.2021.00055 [Jindex] => 0 [CName] => KevinGaston, [CEmail] => Kevin.Gaston@nottingham.ac.uk, [Ris_Time] => 2021-11-02 00:54:27 [Bib_Time] => 2021-11-02 00:54:27 [KeysWordContens] => Targeting protein kinase CK2 in the treatment of cholangiocarcinoma, Cholangiocarcinoma, protein kinase CK2, casein kinase II, dose-dependent synthetic lethality, DNA damage response, apoptosis, methuosis, Cholangiocarcinoma (CCA) is a disease with a very poor prognosis and limited treatment options. Although targeted therapies directed towards specific mutations found in CCA are becoming available and are showing great potential, many tumors do not carry actionable mutations and, in those that do, the emergence of drug resistance is a likely consequence of treatment. Therapeutic targeting of enzymes and other proteins that show elevated activity in CCA cells but which are not altered by mutation is a potential strategy for the treatment of target negative and drug-resistant disease. Protein kinase CK2 (CK2) is a ubiquitously expressed kinase that has increased expression and increased activity in a variety of cancer types including CCA. Several potent CK2 inhibitors are in pre-clinical development or under assessment in a variety of clinical trials often in combination with drugs that induce DNA damage. This review outlines the importance of CK2 in CCA and assesses the progress that has been made in the evaluation of CK2 inhibition as a treatment strategy in this disease. Targeting CK2 based on the expression levels or activity of this protein and/or in combination with drugs that induce DNA damage or inhibit cell cycle progression, could be a viable option for tumors that lack actionable mutations, or for tumors that develop resistance to targeted treatments. ,Padma-Sheela Jayaraman, Kevin Gaston [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [55] => Array ( [ArticleId] => 193 [Create_Time] => 2021-11-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202111/20211102020114.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100256/100256.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100256/100256.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100256/100256_cover.png [JournalsId] => 4 [Title] => A review of molecularly targeted therapy in biliary tract carcinoma: what is the next step? [Abstract] => Patients with unresectable biliary tract carcinomas (BTCs) have a poor prognosis with a median overall survival of fewer than 12 months following systemic chemotherapy. In recent years, the identifi [AbstractComplete] =>Patients with unresectable biliary tract carcinomas (BTCs) have a poor prognosis with a median overall survival of fewer than 12 months following systemic chemotherapy. In recent years, the identification of distinct molecular alterations with corresponding targeted therapies is modifying this therapeutic algorithm. The aim of this review is to present an overview of targeted therapy for BTCs, describing published available data and potential future challenges in ongoing trials. From clinicaltrials.gov online database all ongoing trials for BTCs (any stage) was examinated in July 2021, and data regarding study design, disease characteristics and type of treatments were registered. Oncogenic-driven therapy (targeted therapy) was investigated in 67 trials. According to research, 15 ongoing trials (22.4%) are investigating fibroblast growth factor (FGF) receptor (FGFR)-inhibitors in BTCs. Three (18.7%) are open-label randomized multicenter phase 3 trials, 8 (50%) are single-arm phase two trials, and 4 (25%) are phase one studies. Twelve (17.9%) clinical trials dealt with isocitrate dehydrogenase (IDH) 1/2 targeting therapy either in combination with cisplatin (Cis) and gemcitabine (Gem) as first-line treatment for BTCs or in monotherapy in patients with IDH1 mutant advanced malignancies, including cholangiocarcinoma (CCA). Nine (13.4%) clinical trials tested human epidermal growth factor receptor (HER) 2 targeting therapy. Four (44.4%) studies are phase I trials, two (22.2%) are phase I/II trials, and three (33.3%) phase II trials. Rare molecular alterations in BTCs, such as anaplastic lymphoma kinase (ALK), c-ros oncogene1 receptor tyrosine kinase (ROS1), and v-RAF murine sarcoma viral oncogene homologue B1 (BRAF), are also under investigation in a few trials. Forty-four clinical trials (17.2%) are investigating not oncogenic-driven multitarget therapy like multireceptor tyrosin kinase inhibitors and antiangiogenetic agents. In conclusion, this review shows that BTCs management is experiencing important innovations, especially in biomarker-based patient selection and in the new emerging therapeutic approach. Many ongoing trials could answer questions regarding the role of molecular inhibitors leading to new therapeutic frontiers for molecular subcategories of BTCs.
[Names] => Giacomo Aimar ... Massimo Di Maio [Doi] => 10.37349/etat.2021.00056 [Published] => October 31, 2021 [Viewed] => 1889 [Downloaded] => 79 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00056 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 41 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:448–464 [Recommend] => 0 [Keywords] => Biliary tract carcinomas, target therapy, molecular alterations, isocitrate dehydrogenase, fibroblast growth factor receptor, human epidermal growth factor receptor 2, multitarget therapy [DetailTitle] => Precision Medicine for Cholangiocarcinoma [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/41 [Id] => 100256 [ris] => https://www.explorationpub.com/uploads/Article/A100256/8f87de72a0ca43e37af732b3448991d3.ris [bib] => https://www.explorationpub.com/uploads/Article/A100256/f5597ffcbdae4265842f1508a4335980.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-26 [CitethisArticle] => Aimar G, Paratore C, Zichi C, Marino D, Sperti E, Caglio A, et al. A review of molecularly targeted therapy in biliary tract carcinoma: what is the next step? Explor Target Antitumor Ther. 2021;2:448-64. https://doi.org/10.37349/etat.2021.00056 [Jindex] => 0 [CName] => MassimoDi Maio, [CEmail] => massimo.dimaio@unito.it, [Ris_Time] => 2021-10-28 08:39:23 [Bib_Time] => 2021-10-28 08:39:23 [KeysWordContens] => A review of molecularly targeted therapy in biliary tract carcinoma: what is the next step?, Biliary tract carcinomas, target therapy, molecular alterations, isocitrate dehydrogenase, fibroblast growth factor receptor, human epidermal growth factor receptor 2, multitarget therapy, Patients with unresectable biliary tract carcinomas (BTCs) have a poor prognosis with a median overall survival of fewer than 12 months following systemic chemotherapy. In recent years, the identification of distinct molecular alterations with corresponding targeted therapies is modifying this therapeutic algorithm. The aim of this review is to present an overview of targeted therapy for BTCs, describing published available data and potential future challenges in ongoing trials. From clinicaltrials.gov online database all ongoing trials for BTCs (any stage) was examinated in July 2021, and data regarding study design, disease characteristics and type of treatments were registered. Oncogenic-driven therapy (targeted therapy) was investigated in 67 trials. According to research, 15 ongoing trials (22.4%) are investigating fibroblast growth factor (FGF) receptor (FGFR)-inhibitors in BTCs. Three (18.7%) are open-label randomized multicenter phase 3 trials, 8 (50%) are single-arm phase two trials, and 4 (25%) are phase one studies. Twelve (17.9%) clinical trials dealt with isocitrate dehydrogenase (IDH) 1/2 targeting therapy either in combination with cisplatin (Cis) and gemcitabine (Gem) as first-line treatment for BTCs or in monotherapy in patients with IDH1 mutant advanced malignancies, including cholangiocarcinoma (CCA). Nine (13.4%) clinical trials tested human epidermal growth factor receptor (HER) 2 targeting therapy. Four (44.4%) studies are phase I trials, two (22.2%) are phase I/II trials, and three (33.3%) phase II trials. Rare molecular alterations in BTCs, such as anaplastic lymphoma kinase (ALK), c-ros oncogene1 receptor tyrosine kinase (ROS1), and v-RAF murine sarcoma viral oncogene homologue B1 (BRAF), are also under investigation in a few trials. Forty-four clinical trials (17.2%) are investigating not oncogenic-driven multitarget therapy like multireceptor tyrosin kinase inhibitors and antiangiogenetic agents. In conclusion, this review shows that BTCs management is experiencing important innovations, especially in biomarker-based patient selection and in the new emerging therapeutic approach. Many ongoing trials could answer questions regarding the role of molecular inhibitors leading to new therapeutic frontiers for molecular subcategories of BTCs. ,Giacomo Aimar ... Massimo Di Maio [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [56] => Array ( [ArticleId] => 194 [Create_Time] => 2021-11-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202111/20211101034352.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100257/100257.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100257/100257.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100257/100257_cover.png [JournalsId] => 4 [Title] => Targeted therapy of multiple myeloma [Abstract] => Multiple myeloma (MM) is a malignant proliferative disease of monoclonal plasma cells (PCs) and is characterized by uncontrolled proliferation of PCs and excessive production of specific types of im [AbstractComplete] =>Multiple myeloma (MM) is a malignant proliferative disease of monoclonal plasma cells (PCs) and is characterized by uncontrolled proliferation of PCs and excessive production of specific types of immunoglobulins. Since PCs are terminally differentiated B cells, the World Health Organization (WHO) classifies MM as lymphoproliferative B-cell disease. The incidence of MM is 6–7 cases per 100,000 people in the world every year and the second most common cancer in the blood system. Due to the effects of drug resistance and malignant regeneration of MM cells in the microenvironment, all current treatment methods can prolong both overall and symptom-free survival rates of patients with MM but cannot cure MM. Both basic and clinical studies have proven that targeted therapy leads to a clear and significant prolongation of the survival of patients with MM, but when the disease recurs again, resistance to the previous treatment will occur. Therefore, the discovery of new targets and treatment methods plays a vital role in the treatment of MM. This article introduces and summarizes targeted MM therapy, potential new targets, and future precision medicine in MM.
[Names] => Shan Zhou, Renxi Wang [Doi] => 10.37349/etat.2021.00057 [Published] => October 31, 2021 [Viewed] => 1654 [Downloaded] => 53 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00057 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:465–480 [Recommend] => 0 [Keywords] => Multiple myeloma, targeted therapy, potential targets, immune-based therapies, precision medicine [DetailTitle] => [DetailUrl] => [Id] => 100257 [ris] => https://www.explorationpub.com/uploads/Article/A100257/5d29fedb81b5a1c0aa42cab1a8032bfc.ris [bib] => https://www.explorationpub.com/uploads/Article/A100257/7532947dc57fa9f031b74aeef14f777d.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Zhou S, Wang R. Targeted therapy of multiple myeloma. Explor Target Antitumor Ther. 2021;2:465-80. https://doi.org/10.37349/etat.2021.00057 [Jindex] => 0 [CName] => RenxiWang, [CEmail] => renxi_wang@ccmu.edu.cn, [Ris_Time] => 2021-10-28 09:40:50 [Bib_Time] => 2021-10-28 09:40:50 [KeysWordContens] => Targeted therapy of multiple myeloma, Multiple myeloma, targeted therapy, potential targets, immune-based therapies, precision medicine, Multiple myeloma (MM) is a malignant proliferative disease of monoclonal plasma cells (PCs) and is characterized by uncontrolled proliferation of PCs and excessive production of specific types of immunoglobulins. Since PCs are terminally differentiated B cells, the World Health Organization (WHO) classifies MM as lymphoproliferative B-cell disease. The incidence of MM is 6–7 cases per 100,000 people in the world every year and the second most common cancer in the blood system. Due to the effects of drug resistance and malignant regeneration of MM cells in the microenvironment, all current treatment methods can prolong both overall and symptom-free survival rates of patients with MM but cannot cure MM. Both basic and clinical studies have proven that targeted therapy leads to a clear and significant prolongation of the survival of patients with MM, but when the disease recurs again, resistance to the previous treatment will occur. Therefore, the discovery of new targets and treatment methods plays a vital role in the treatment of MM. This article introduces and summarizes targeted MM therapy, potential new targets, and future precision medicine in MM. ,Shan Zhou, Renxi Wang [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [57] => Array ( [ArticleId] => 197 [Create_Time] => 2021-11-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202112/20211213091401.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100258/100258.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100258/100258.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100258/100258-cover.png [JournalsId] => 4 [Title] => Performing oncological procedures during COVID-19 outbreak: a picture from an Italian cancer center [Abstract] => Aim: Since SARS-CoV-2 infection rapidly spread around the world, Italy has quickly become one of the most affected countries. Healthcare systems introduced strict infection control measures to ensu [AbstractComplete] =>Since SARS-CoV-2 infection rapidly spread around the world, Italy has quickly become one of the most affected countries. Healthcare systems introduced strict infection control measures to ensure optimal care, especially in frail groups such as cancer patients (pts). This study investigated the efficacy of SARS-CoV-2 pre-procedure screening and whether COVID-19 influenced timely diagnosis and therapy.
Data of oncological procedures of pts with confirmed or suspected cancer diagnosis, treated at Oncology Department or coming from Emergency Department of San Luigi Gonzaga Hospital between June 2020 and March 2021 were retrospectively collected. A nasopharyngeal swab (NPS) was performed in outpatients 24/48 h before procedures. Inpatients were tested by NPS before and after hospitalization.
Two hundred and twenty-one pts were included in this analysis. Median age was 73 years, males were 58%. Eastern Cooperative Oncology Group (ECOG) Performance Status was 0 or 1 in 88% of pts. The most frequent cancer type was lung cancer (57%). Stages IV were 77%. Two hundred and forty-three scheduled procedures were performed with diagnostic (n: 142; 58%), therapeutic (n: 55; 23%), and palliative (n: 46; 19%) intent. One hundred and four and 139 procedures were performed in out- and in-pts, respectively. Of the 234 NPS performed, 10 (4%) were positive. Two pts were infected during hospitalization, 8 in community. Most of them were asymptomatic, while only 2 had mild symptoms. Eight procedures (3%) were postponed, 1 cancelled, while 2 were performed in positive pts. Median time to resolution of the infection was 17 days (11–36). Median delay in the procedures was 25 days (14–55). Five pts started systemic treatment, after a median time of 37.5 days (13–57).
SARS-CoV-2 infection led to the postponement of a small, but not negligible percentage of oncological procedures. However, the low infection rate observed suggests that structured screening for COVID-19 is critical for the best management of scheduled procedures during pandemic.
Adjuvant hormonal therapy is one of the most important treatments of hormone-receptor-positive breast cancer and includes selective estrogen receptor modulators, aromatase inhibitors, and luteinizing hormone-releasing hormone analogs. In patients receiving these drugs, a progressive recession of frontal-temporal hairlines is often observed, such as a certain grade of hair miniaturization in the same areas and the central scalp area, producing a pseudo-female androgenic alopecia, which has to be considered oncotherapy-induced alopecia. The aim of this work, is to describe the clinical aspects and pathogenesis of this type of alopecia and to analyze the different drugs which have been proposed until now. The authors concude that topical hormones should not be considered as a therapeutic approach because of their direct or indirect oncogenic potential. A therapeutic approach that could be both safe and effective is proposed.
[Names] => Alfredo Rossi ... Marta Carlesimo [Doi] => 10.37349/etat.2021.00059 [Published] => October 31, 2021 [Viewed] => 1555 [Downloaded] => 32 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00059 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 48 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:490–495 [Recommend] => 0 [Keywords] => Alopecia, hormonal therapy, breast cancer [DetailTitle] => Endocrine Resistant Breast Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/48 [Id] => 100259 [ris] => https://www.explorationpub.com/uploads/Article/A100259/70c70e0519d77432b2f669d0191e4e09.ris [bib] => https://www.explorationpub.com/uploads/Article/A100259/efad3b4f1a84be7652125fc1154bb6bd.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-26 [CitethisArticle] => Rossi A, Caro G, Magri F, Fortuna MC, Carlesimo M. Clinical aspect, pathogenesis and therapy options of alopecia induced by hormonal therapy for breast cancer. Explor Target Antitumor Ther. 2021;2:490-5. https://doi.org/10.37349/etat.2021.00059 [Jindex] => 0 [CName] => GemmaCaro, [CEmail] => gemmacaro90@gmail.com, [Ris_Time] => 2021-11-02 01:06:46 [Bib_Time] => 2021-11-02 01:06:46 [KeysWordContens] => Clinical aspect, pathogenesis and therapy options of alopecia induced by hormonal therapy for breast cancer, Alopecia, hormonal therapy, breast cancer, Adjuvant hormonal therapy is one of the most important treatments of hormone-receptor-positive breast cancer and includes selective estrogen receptor modulators, aromatase inhibitors, and luteinizing hormone-releasing hormone analogs. In patients receiving these drugs, a progressive recession of frontal-temporal hairlines is often observed, such as a certain grade of hair miniaturization in the same areas and the central scalp area, producing a pseudo-female androgenic alopecia, which has to be considered oncotherapy-induced alopecia. The aim of this work, is to describe the clinical aspects and pathogenesis of this type of alopecia and to analyze the different drugs which have been proposed until now. The authors concude that topical hormones should not be considered as a therapeutic approach because of their direct or indirect oncogenic potential. A therapeutic approach that could be both safe and effective is proposed. ,Alfredo Rossi ... Marta Carlesimo [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [59] => Array ( [ArticleId] => 203 [Create_Time] => 2021-11-17 [zipUrl] => https://www.explorationpub.com/uploads/zip/202112/20211231052324.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100260/100260.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100260/100260.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100260/100260_cover.png [JournalsId] => 4 [Title] => Proteolysis-targeting chimeras and their implications in breast cancer [Abstract] => Breast cancer (BC) is a highly heterogeneous neoplasm of the mammary tissue, causing the deaths of a large number of women worldwide. Nearly 70% and 20% of BC cases are estro [AbstractComplete] =>Breast cancer (BC) is a highly heterogeneous neoplasm of the mammary tissue, causing the deaths of a large number of women worldwide. Nearly 70% and 20% of BC cases are estrogen receptor alpha positive (ERα+) and human epidermal growth factor receptor 2-positive (HER2+), respectively; therefore, ER and HER2 targeted therapies have been employed in BC treatment. However, resistance to these therapies has been reported, indicating a need for developing novel therapeutic strategies. Proteolysis-targeting chimeras (PROTACs) are new, promising therapeutic tools designed with a bimodular structure: one module allows specific binding to target proteins, and the other module allows efficient degradation of these target proteins. In this paper, PROTACs and their potential in controlling the progression of ERα and HER2+ BC are discussed.
[Names] => Angeles C. Tecalco-Cruz ... Alberto Rojas-Ochoa [Doi] => 10.37349/etat.2021.00060 [Published] => December 31, 2021 [Viewed] => 2280 [Downloaded] => 86 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00060 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 27 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:496–510 [Recommend] => 0 [Keywords] => Estrogen receptor alpha, breast cancer, degradation via the ubiquitin-proteasome system, proteolysis-targeting chimeras [DetailTitle] => Proteolysis Targeting Chimera (PROTAC) [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/27 [Id] => 100260 [ris] => https://www.explorationpub.com/uploads/Article/A100260/25fa166e2f56c9fc294c6ed184bd3acd.ris [bib] => https://www.explorationpub.com/uploads/Article/A100260/bd8a2fd38ac79b24ebb0f09bde848a58.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-26 [CitethisArticle] => Tecalco-Cruz AC, Zepeda-Cervantes J, Ramírez-Jarquín JO, Rojas-Ochoa A. Proteolysis-targeting chimeras and their implications in breast cancer. Explor Target Antitumor Ther. 2021;2:496-510. https://doi.org/10.37349/etat.2021.00060 [Jindex] => 0 [CName] => Angeles C.Tecalco-Cruz, [CEmail] => angeles.tecalco@uacm.edu.mx, [Ris_Time] => 2021-12-31 05:23:25 [Bib_Time] => 2021-12-31 05:23:25 [KeysWordContens] => Proteolysis-targeting chimeras and their implications in breast cancer, Estrogen receptor alpha, breast cancer, degradation via the ubiquitin-proteasome system, proteolysis-targeting chimeras, Breast cancer (BC) is a highly heterogeneous neoplasm of the mammary tissue, causing the deaths of a large number of women worldwide. Nearly 70% and 20% of BC cases are estrogen receptor alpha positive (ERα+) and human epidermal growth factor receptor 2-positive (HER2+), respectively; therefore, ER and HER2 targeted therapies have been employed in BC treatment. However, resistance to these therapies has been reported, indicating a need for developing novel therapeutic strategies. Proteolysis-targeting chimeras (PROTACs) are new, promising therapeutic tools designed with a bimodular structure: one module allows specific binding to target proteins, and the other module allows efficient degradation of these target proteins. In this paper, PROTACs and their potential in controlling the progression of ERα and HER2+ BC are discussed. ,Angeles C. Tecalco-Cruz ... Alberto Rojas-Ochoa [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [60] => Array ( [ArticleId] => 206 [Create_Time] => 2021-12-02 [zipUrl] => https://www.explorationpub.com/uploads/zip/202112/20211231052938.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100261/100261.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100261/100261.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100261/100261_cover.png [JournalsId] => 4 [Title] => The clinical advances of proteolysis targeting chimeras in oncology [Abstract] => Proteolysis targeting chimeras (PROTACs) are a class of small molecules designed to target proteins for degradation. Their novel and unique modes of action provide PROTACs with the potential for the [AbstractComplete] =>Proteolysis targeting chimeras (PROTACs) are a class of small molecules designed to target proteins for degradation. Their novel and unique modes of action provide PROTACs with the potential for their application in the management of both solid and hematologic malignancies. Since its initial discovery, the technology of targeted protein degradation, especially in the form of PROTACs, has had significant advances. A number of PROTACs have entered a late stage of preclinical development. Several of them are either in phase 1/2 clinical trials or approaching approval for initial clinical evaluation. This article discusses the preclinical and clinical findings of PROTACs of clinically relevant protein targets in cancer.
[Names] => Hao Xie ... Jason B. Fleming [Doi] => 10.37349/etat.2021.00061 [Published] => December 31, 2021 [Viewed] => 4112 [Downloaded] => 213 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00061 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 27 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:511–521 [Recommend] => 0 [Keywords] => proteolysis targeting chimera, phase 1, clinical trial [DetailTitle] => Proteolysis Targeting Chimera (PROTAC) [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/27 [Id] => 100261 [ris] => https://www.explorationpub.com/uploads/Article/A100261/261e38b4d6a7983a07dcab531bb2d948.ris [bib] => https://www.explorationpub.com/uploads/Article/A100261/7388cdc25f229e4fc8ed8b98cf143ce6.bib [ens] => [Cited] => 17 [Cited_Time] => 2024-04-27 [CitethisArticle] => Xie H, Liu J, Alem Glison DM, Fleming JB. The clinical advances of proteolysis targeting chimeras in oncology. Explor Target Antitumor Ther. 2021;2:511-21. https://doi.org/10.37349/etat.2021.00061 [Jindex] => 0 [CName] => HaoXie, [CEmail] => hao.xie@moffitt.org, [Ris_Time] => 2021-12-31 05:29:39 [Bib_Time] => 2021-12-31 05:29:39 [KeysWordContens] => The clinical advances of proteolysis targeting chimeras in oncology, proteolysis targeting chimera, phase 1, clinical trial, Proteolysis targeting chimeras (PROTACs) are a class of small molecules designed to target proteins for degradation. Their novel and unique modes of action provide PROTACs with the potential for their application in the management of both solid and hematologic malignancies. Since its initial discovery, the technology of targeted protein degradation, especially in the form of PROTACs, has had significant advances. A number of PROTACs have entered a late stage of preclinical development. Several of them are either in phase 1/2 clinical trials or approaching approval for initial clinical evaluation. This article discusses the preclinical and clinical findings of PROTACs of clinically relevant protein targets in cancer. ,Hao Xie ... Jason B. Fleming [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [61] => Array ( [ArticleId] => 209 [Create_Time] => 2021-12-07 [zipUrl] => https://www.explorationpub.com/uploads/zip/202201/20220104034048.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100262/100262.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100262/100262.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100262/100262_cover.png [JournalsId] => 4 [Title] => Immunotherapy in head and neck squamous cell carcinoma and rare head and neck malignancies [Abstract] => The dismal prognosis of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) prompted recent advances in the field of therapeutic approaches beyond cytotoxic cancer therapy. In r [AbstractComplete] =>The dismal prognosis of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) prompted recent advances in the field of therapeutic approaches beyond cytotoxic cancer therapy. In recent years, the deeper and increasing knowledge on the genomic landscape and the upcoming new data on immunotherapy enacted by HNSCCs have led to successful therapeutic targeting of the immune system. Immune checkpoint inhibitors (ICIs) have changed state of the art in R/M patients and could have a potential role even in early disease. The purpose of this work is to summarize the role of immunotherapy for R/M HNSCC in clinical practice, with insights about future perspectives. Updated immunotherapy results in other R/M head and neck cancers such as thyroid, salivary glands, nasopharynx, sinonasal cancers, and nuclear protein in testis (NUT) are presented.
[Names] => Stefano Cavalieri ... Laura D. Locati [Doi] => 10.37349/etat.2021.00062 [Published] => December 31, 2021 [Viewed] => 2245 [Downloaded] => 95 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00062 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 34 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:522–542 [Recommend] => 0 [Keywords] => Head and neck cancer, immune checkpoint inhibitors, rare cancer [DetailTitle] => Immunotherapy in Cancer Patients [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/34 [Id] => 100262 [ris] => https://www.explorationpub.com/uploads/Article/A100262/b9ba3fcf3004bef16fbfaf5bc535a1e3.ris [bib] => https://www.explorationpub.com/uploads/Article/A100262/deeee57a9d6c7a8453e112030a76f282.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-26 [CitethisArticle] => Cavalieri S, Filippini DM, Ottini A, Bergamini C, Resteghini C, Colombo E, et al. Immunotherapy in head and neck squamous cell carcinoma and rare head and neck malignancies. Explor Target Antitumor Ther. 2021;2:522-42. https://doi.org/10.37349/etat.2021.00062 [Jindex] => 0 [CName] => StefanoCavalieri, [CEmail] => stefano.cavalieri@istitutotumori.mi.it, [Ris_Time] => 2021-12-31 07:37:39 [Bib_Time] => 2021-12-31 07:37:39 [KeysWordContens] => Immunotherapy in head and neck squamous cell carcinoma and rare head and neck malignancies, Head and neck cancer, immune checkpoint inhibitors, rare cancer, The dismal prognosis of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) prompted recent advances in the field of therapeutic approaches beyond cytotoxic cancer therapy. In recent years, the deeper and increasing knowledge on the genomic landscape and the upcoming new data on immunotherapy enacted by HNSCCs have led to successful therapeutic targeting of the immune system. Immune checkpoint inhibitors (ICIs) have changed state of the art in R/M patients and could have a potential role even in early disease. The purpose of this work is to summarize the role of immunotherapy for R/M HNSCC in clinical practice, with insights about future perspectives. Updated immunotherapy results in other R/M head and neck cancers such as thyroid, salivary glands, nasopharynx, sinonasal cancers, and nuclear protein in testis (NUT) are presented. ,Stefano Cavalieri ... Laura D. Locati [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [62] => Array ( [ArticleId] => 221 [Create_Time] => 2021-12-14 [zipUrl] => https://www.explorationpub.com/uploads/zip/202112/20211231055713.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100263/100263.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100263/100263.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100263/100263_cover.png [JournalsId] => 4 [Title] => Alterations in the Ca2+ toolkit in oesophageal adenocarcinoma [Abstract] => Aim: To investigate alterations in transcription of genes, encoding Ca2+ toolkit proteins, in oesophageal adenocarcinoma (OAC) and to assess associations between gene expression, tumor [AbstractComplete] =>To investigate alterations in transcription of genes, encoding Ca2+ toolkit proteins, in oesophageal adenocarcinoma (OAC) and to assess associations between gene expression, tumor grade, nodal-metastatic stage, and patient survival.
The expression of 275 transcripts, encoding components of the Ca2+ toolkit, was analyzed in two OAC datasets: the Cancer Genome Atlas [via the University of Alabama Cancer (UALCAN) portal] and the oesophageal-cancer, clinical, and molecular stratification [Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS)] dataset. Effects of differential expression of these genes on patient survival were determined using Kaplan-Meier log-rank tests. OAC grade- and metastatic-stage status was investigated for a subset of genes. Adjustment for the multiplicity of testing was made throughout.
Of the 275 Ca2+-toolkit genes analyzed, 75 displayed consistent changes in expression between OAC and normal tissue in both datasets. The channel-encoding genes, N-methyl-D-aspartate receptor 2D (GRIN2D), transient receptor potential (TRP) ion channel classical or canonical 4 (TRPC4), and TRP ion channel melastatin 2 (TRPM2) demonstrated the greatest increase in expression in OAC in both datasets. Nine genes were consistently upregulated in both datasets and were also associated with improved survival outcomes. The 6 top-ranking genes for the weighted significance of altered expression and survival outcomes were selected for further analysis: voltage-gated Ca2+ channel subunit α 1D (CACNA1D), voltage-gated Ca2+ channel auxiliary subunit α2 δ4 (CACNA2D4), junctophilin 1 (JPH1), acid-sensing ion channel 4 (ACCN4), TRPM5, and secretory pathway Ca2+ ATPase 2 (ATP2C2). CACNA1D, JPH1, and ATP2C2 were also upregulated in advanced OAC tumor grades and nodal-metastatic stages in both datasets.
This study has unveiled alterations of the Ca2+ toolkit in OAC, compared to normal tissue. Such Ca2+ signalling findings are consistent with those from studies on other cancers. Genes that were consistently upregulated in both datasets might represent useful markers for patient diagnosis. Genes that were consistently upregulated, and which were associated with improved survival, might be useful markers for patient outcome. These survival-associated genes may also represent targets for the development of novel chemotherapeutic agents.
Direct analytical comparison of two major drug-linkers in the antibody-drug conjugate (ADC) field was conducted.
Four different analytical methods [AlogP calculation, reverse phase (RP) high-performance liquid chromatography (HPLC; RP-HPLC), size exclusion chromatography HPLC (SEC-HPLC), and differential scanning calorimetry (DSC)] were tested for this comparison.
Maytansinoid-based ADCs showed less hydrophobicity than auristatin-based ADCs. Regardless of the drug-linker and drug-to-antibody ratios (DARs), the stability detected by DSC was decreased by conjugation.
The cost and time-efficient analytical comparison described in this manuscript may be useful information for an initial characterization of ADCs prior to detailed biological studies.
Obesity has dramatically increased over the past fifty years. In the last decade, it has been noted that augmented body mass, metabolic abnormalities, and the relevant “obese” tumor microenvironment (TME) are connected with signaling molecular networks, which in turn, may contribute to aggressive tumor biology in some patients with breast malignancies. This article presents the associations between obesity, metabolic derangements, inflammatory processes in the adipose tissue or TME, and aggressive behavior of triple-negative breast cancer (TNBC) in African American (AA) women. It also describes some abnormal molecular signaling patterns in the “obese” TME with relevance to TNBC biology. Ethnic disparities in TNBC can be due to a variety of biological features (e.g., genetic mutations and tumor heterogeneity), comorbidities (e.g., cardio-metabolic diseases, including diabetes mellitus), and reproductive factors (e.g., multiparty or short breastfeeding period). Such a constellation of biological variables potentially leads to the association between obesity, metabolic derangements, inflammatory processes in the adipose tissue or TME, and aggressive behavior of TNBC in AA women. Since the TNBC and its TME can display very aggressive behavior, it is crucial that the afflicted AA women make efforts to maintain healthy body weight, “flexible” metabolism, and a well-functioning immune system. Further studies are merited to explore the multi-disciplinary factors that can affect TNBC prevention, management, and outcomes to optimize treatment strategies and survival among AA women.
[Names] => Katarzyna Rygiel [Doi] => 10.37349/etat.2021.00066 [Published] => December 31, 2021 [Viewed] => 1454 [Downloaded] => 55 [Subject] => Review [Year] => 2021 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2021.00066 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 48 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2021;2:602–616 [Recommend] => 0 [Keywords] => Triple-negative breast cancer, African American, body mass index, waist-to-hip ratio, central obesity, cytokines, inflammation, tumor microenvironment [DetailTitle] => Endocrine Resistant Breast Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/48 [Id] => 100266 [ris] => https://www.explorationpub.com/uploads/Article/A100266/6760d5827f019fc6a37d3d7e6b253879.ris [bib] => https://www.explorationpub.com/uploads/Article/A100266/46653022d094824270b212d3667afd03.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Rygiel K. Interface between obesity with dysfunctional metabolism and inflammation, and the triple-negative breast cancer in African American women. Explor Target Antitumor Ther. 2021;2:602-16. https://doi.org/10.37349/etat.2021.00066 [Jindex] => 0 [CName] => KatarzynaRygiel, [CEmail] => kasiaalpha@yahoo.co.uk, [Ris_Time] => 2021-12-31 07:43:46 [Bib_Time] => 2021-12-31 07:43:46 [KeysWordContens] => Interface between obesity with dysfunctional metabolism and inflammation, and the triple-negative breast cancer in African American women, Triple-negative breast cancer, African American, body mass index, waist-to-hip ratio, central obesity, cytokines, inflammation, tumor microenvironment, Obesity has dramatically increased over the past fifty years. In the last decade, it has been noted that augmented body mass, metabolic abnormalities, and the relevant “obese” tumor microenvironment (TME) are connected with signaling molecular networks, which in turn, may contribute to aggressive tumor biology in some patients with breast malignancies. This article presents the associations between obesity, metabolic derangements, inflammatory processes in the adipose tissue or TME, and aggressive behavior of triple-negative breast cancer (TNBC) in African American (AA) women. It also describes some abnormal molecular signaling patterns in the “obese” TME with relevance to TNBC biology. Ethnic disparities in TNBC can be due to a variety of biological features (e.g., genetic mutations and tumor heterogeneity), comorbidities (e.g., cardio-metabolic diseases, including diabetes mellitus), and reproductive factors (e.g., multiparty or short breastfeeding period). Such a constellation of biological variables potentially leads to the association between obesity, metabolic derangements, inflammatory processes in the adipose tissue or TME, and aggressive behavior of TNBC in AA women. Since the TNBC and its TME can display very aggressive behavior, it is crucial that the afflicted AA women make efforts to maintain healthy body weight, “flexible” metabolism, and a well-functioning immune system. Further studies are merited to explore the multi-disciplinary factors that can affect TNBC prevention, management, and outcomes to optimize treatment strategies and survival among AA women. ,Katarzyna Rygiel [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [65] => Array ( [ArticleId] => 238 [Create_Time] => 2021-12-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202204/20220421084027.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100265/100265.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100265/100265.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100265/100265_cover.png [JournalsId] => 4 [Title] => The bromodomain and extra-terminal domain degrader MZ1 exhibits preclinical anti-tumoral activity in diffuse large B-cell lymphoma of the activated B cell-like type [Abstract] => Aim: Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that play a fundamental role in transcription regulation. Preclinical and early clinical evidence sustain BET targ [AbstractComplete] =>Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that play a fundamental role in transcription regulation. Preclinical and early clinical evidence sustain BET targeting as an anti-cancer approach. BET degraders are chimeric compounds comprising of a BET inhibitor, which allows the binding to BET bromodomains, linked to a small molecule, binder for an E3 ubiquitin ligase complex, triggering BET proteins degradation via the proteasome. These degraders, called proteolysis-targeting chimeras (PROTACs), can exhibit greater target specificity compared to BET inhibitors and overcome some of their limitations, such as the upregulation of the BET proteins themselves. Here are presented data on the anti-tumor activity and the mechanism of action of the BET degrader MZ1 in diffuse large B cell lymphoma (DLBCL) of the activated B-cell like (ABC, ABC DLBCL), using a BET inhibitor as a comparison.
Established lymphoma cell lines were exposed for 72 h to increasing doses of the compounds. Cell proliferation was evaluated by using an 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliumbromide (MTT) assay. Fluorescent-Activated Cell Sorter (FACS) analysis was performed to measure apoptotic activation and RNA sequencing (RNA-Seq) to study the transcriptional changes induced by the compounds.
MZ1, and not its negative control epimer cisMZ1, was very active with a median half maximal inhibitory concentration (IC50) of 49 nmol/L. MZ1 was more in vitro active than the BET inhibitor birabresib (OTX015). Importantly, MZ1 induced cell death in all the ABC DLBCL cell lines, while the BET inhibitor was cytotoxic only in a fraction of them. BET degrader and inhibitor shared partially similar changes at transcriptome level but the MZ1 effect was stronger and overlapped with that caused cyclin-dependent kinase 9 (CDK9) inhibition.
The BET degrader MZ1 had strong cytotoxic activity in all the ABC DLBCL cell lines that were tested, and, at least in vitro, it elicited more profound effects than BET inhibitors, and encourages further investigations.
Targeted immunotherapy has arisen over the past decade to the forefront of cancer care. Notably, targeted therapies such as antibody-drug conjugates (ADCs) are becoming more recognized for a novel approach in cancer treatment. The mechanism of action of ADCs incorporates a monoclonal antibody portion directed against the tumor cell antigen and attached to the tumoricidal portion via chemical linkage. The binding of the monoclonal antibody portion allows for tumor cell internalization of the ADC and precise release of the toxic payload within the cancer cell. Multiple myeloma (MM) is an incurable cancer for which belantamab mafodotin was the first-in-class ADC to achieve United States Food and Drug Administration (FDA) approval for treatment of this disease. Clinical trials are currently evaluating other ADCs in the treatment of MM. In this review, a look at the current ADCs being tested in MM clinical trials with a focus on those that are more promising and a potential next-in-line for FDA approval for treatment of MM is discussed.
[Names] => Monique Hartley-Brown, Paul Richardson [Doi] => 10.37349/etat.2022.00067 [Published] => January 14, 2022 [Viewed] => 2738 [Downloaded] => 118 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00067 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 45 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:1–10 [Recommend] => 0 [Keywords] => Antibody-drug conjugates, multiple myeloma, cancer, immunotherapy, targeted therapy [DetailTitle] => Antibody-Drug Conjugates [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/45 [Id] => 100267 [ris] => https://www.explorationpub.com/uploads/Article/A100267/5b12a38019ca8ac83a0927592d4d6adc.ris [bib] => https://www.explorationpub.com/uploads/Article/A100267/47dfe8d3c33e3bb78bb53939be268724.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-27 [CitethisArticle] => Hartley-Brown M, Richardson P. Antibody-drug conjugate therapies in multiple myeloma—what’s next on the horizon? Explor Target Antitumor Ther. 2022;3:1–10. https://doi.org/10.37349/etat.2022.00067 [Jindex] => 0 [CName] => MoniqueHartley-Brown, [CEmail] => MoniqueA_Hartley-Brown@DFCI.Harvard.edu, [Ris_Time] => 2022-01-20 09:13:40 [Bib_Time] => 2022-01-20 09:13:40 [KeysWordContens] => Antibody-drug conjugate therapies in multiple myeloma—what’s next on the horizon?, Antibody-drug conjugates, multiple myeloma, cancer, immunotherapy, targeted therapy, Targeted immunotherapy has arisen over the past decade to the forefront of cancer care. Notably, targeted therapies such as antibody-drug conjugates (ADCs) are becoming more recognized for a novel approach in cancer treatment. The mechanism of action of ADCs incorporates a monoclonal antibody portion directed against the tumor cell antigen and attached to the tumoricidal portion via chemical linkage. The binding of the monoclonal antibody portion allows for tumor cell internalization of the ADC and precise release of the toxic payload within the cancer cell. Multiple myeloma (MM) is an incurable cancer for which belantamab mafodotin was the first-in-class ADC to achieve United States Food and Drug Administration (FDA) approval for treatment of this disease. Clinical trials are currently evaluating other ADCs in the treatment of MM. In this review, a look at the current ADCs being tested in MM clinical trials with a focus on those that are more promising and a potential next-in-line for FDA approval for treatment of MM is discussed. ,Monique Hartley-Brown, Paul Richardson [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [67] => Array ( [ArticleId] => 248 [Create_Time] => 2022-01-30 [zipUrl] => https://www.explorationpub.com/uploads/zip/202202/20220203012312.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100268/100268.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100268/100268.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100268/100268_cover.png [JournalsId] => 4 [Title] => Bcl-2-like protein-10 increases aggressive features of melanoma cells [Abstract] => Aim: B-cell lymphoma-2 (Bcl-2)-like protein-10 (Bcl2L10) is the less studied member of Bcl-2 family proteins, with the controversial role in different cancer histotypes. Very recently, Bcl2L10 ex [AbstractComplete] =>B-cell lymphoma-2 (Bcl-2)-like protein-10 (Bcl2L10) is the less studied member of Bcl-2 family proteins, with the controversial role in different cancer histotypes. Very recently, Bcl2L10 expression in melanoma tumor specimens and its role in melanoma response to therapy have been demonstrated. Here, the involvement of Bcl2L10 on the in vitro and in vivo properties associated with melanoma aggressive features has been investigated.
Endogenous Bcl2L10 protein expression was detected by western blotting analysis in a panel of patient-derived and commercially available human melanoma cells. In vitro assays to evaluate clonogenicity, cell proliferation, cell migration, cell invasion, and in vitro capillary-like structure formation [vasculogenic mimicry (VM)] have been performed by using human melanoma cells stably overexpressing Bcl2L10 or transiently transfected for loss/gain function of Bcl2L10, grown under two- or three-dimensional (3D) conditions Xenograft melanoma model was employed to evaluate in vivo tumor growth and angiogenesis.
Results demonstrated that Bcl2L10 acts as an inducer of in vitro cell migration, invasion, and VM, while in vitro cell proliferation, in vivo tumor growth, as well as colony formation properties were not affected. Dissecting different signaling pathways, it was found that Bcl2L10 positively affects the phosphorylation of extracellular-signal-regulated kinase (ERK) and the expression of markers of cell invasion, such as urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinases (MMPs). Of note, Bcl2L10-dependent in vitro migration, invasion, and VM are linked to uPAR. Bcl2L10 also negatively regulates the intracellular calcium level. Finally, reduced invasion capability in 3D spheroid invasion assay of melanoma cells transiently overexpressing Bcl2L10 was observed after treatment with inhibitors of MMPs and uPAR.
Overall, data reported in this paper provide evidence supporting a positive role of Bcl2L10 in melanoma aggressive features.
Antibody-drug conjugates (ADCs) have changed the treatment of breast cancer (BC) in more recent years. BC is a heterogenous group of malignancies with a broad range of histopathological characteristics. ADCs represent a class of therapeutics that combines an antigen-specific antibody backbone bound to a potent cytotoxic agent (the payload), via a linker, contributing to an improved therapeutic index. Currently, three ADCs received approval by the US Food and Drug Administration (FDA) and are in routine clinical use in different treatment settings; many more ADCs are in earlier and later stages of development, and their future approval will improve treatment options for patients with advanced but potentially also early-stage BC over time. Just recently, the results of three phase 3 trials (ASCENT, TULIP, and DESTINY-Breast03) evaluating sacituzumab govitecan (SG), trastuzumab duocarmazine, and trastuzumab deruxtecan (T-DXd) in different treatment settings were presented and showed promising results. This overview focuses on the newer ADCs, including T-DXd and SG, their pharmacology, mechanisms of action, and relevant studies. In addition, the latest results from trials investigating some newer ADCs, in further stages of development are presented.
[Names] => Kira-Lee Koster ... Markus Joerger [Doi] => 10.37349/etat.2022.00069 [Published] => February 24, 2022 [Viewed] => 3237 [Downloaded] => 92 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00069 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 45 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:27–36 [Recommend] => 1 [Keywords] => Antibody-drug conjugates, triple-negative breast cancer, human epidermal growth factor receptor 2-positive breast cancer [DetailTitle] => Antibody-Drug Conjugates [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/45 [Id] => 100269 [ris] => https://www.explorationpub.com/uploads/Article/A100269/619b8268c909d348e43668b12a0f7e53.ris [bib] => https://www.explorationpub.com/uploads/Article/A100269/dd5b069a9b0bf9af385e3fd131fd7c9e.bib [ens] => [Cited] => 15 [Cited_Time] => 2024-04-27 [CitethisArticle] => Koster KL, Huober J, Joerger M. New antibody-drug conjugates (ADCs) in breast cancer—an overview of ADCs recently approved and in later stages of development. Explor Target Antitumor Ther. 2022;3:27–36. https://doi.org/10.37349/etat.2022.00069 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-02-24 03:26:39 [Bib_Time] => 2022-02-24 03:26:39 [KeysWordContens] => New antibody-drug conjugates (ADCs) in breast cancer—an overview of ADCs recently approved and in later stages of development, Antibody-drug conjugates, triple-negative breast cancer, human epidermal growth factor receptor 2-positive breast cancer, Antibody-drug conjugates (ADCs) have changed the treatment of breast cancer (BC) in more recent years. BC is a heterogenous group of malignancies with a broad range of histopathological characteristics. ADCs represent a class of therapeutics that combines an antigen-specific antibody backbone bound to a potent cytotoxic agent (the payload), via a linker, contributing to an improved therapeutic index. Currently, three ADCs received approval by the US Food and Drug Administration (FDA) and are in routine clinical use in different treatment settings; many more ADCs are in earlier and later stages of development, and their future approval will improve treatment options for patients with advanced but potentially also early-stage BC over time. Just recently, the results of three phase 3 trials (ASCENT, TULIP, and DESTINY-Breast03) evaluating sacituzumab govitecan (SG), trastuzumab duocarmazine, and trastuzumab deruxtecan (T-DXd) in different treatment settings were presented and showed promising results. This overview focuses on the newer ADCs, including T-DXd and SG, their pharmacology, mechanisms of action, and relevant studies. In addition, the latest results from trials investigating some newer ADCs, in further stages of development are presented. ,Kira-Lee Koster ... Markus Joerger [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [69] => Array ( [ArticleId] => 268 [Create_Time] => 2022-02-25 [zipUrl] => https://www.explorationpub.com/uploads/zip/202202/20220225051817.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100270/100270.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100270/100270.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100270/100270_cover.png [JournalsId] => 4 [Title] => B-cell receptor dependent phagocytosis and presentation of particulate antigen by chronic lymphocytic leukemia cells [Abstract] => Aim: T-helper cells could play an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), a common B-cell neoplasm. Although CLL cells can present soluble antigens targeted from [AbstractComplete] =>T-helper cells could play an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), a common B-cell neoplasm. Although CLL cells can present soluble antigens targeted from the B-cell receptor to T-helper cells via major histocompatibility complex (MHC) class II, antigens recognized by some CLL cells may be encountered in a particulate form. Here the ability of CLL cells to internalize and present anti-immunoglobulin M (IgM) beads as a model for the interaction of CLL cells with particulate antigens was investigated.
The effect of anti-IgM beads on antigen presentation pathways was analyzed using RNA-seq and internalization of anti-IgM beads by primary CLL cells was investigated using confocal microscopy and flow cytometry. Antigen presentation was investigated by analyzing activation of a T-cell line expressing a T-cell receptor specific for a peptide derived from mouse κ light chains after incubating CLL cells with a mouse κ light chain-containing anti-IgM monoclonal antibody. Kinase inhibitors were used to characterize the pathways mediating internalization and antigen presentation.
Stimulation of surface IgM of CLL cells increased expression of the antigen presentation machinery and CLL cells were able to phagocytose anti-IgM beads. Internalization of anti-IgM beads was associated with MHC class II-restricted activation of cognate T-helper cells. Antigen presentation by CLL cells was dependent on activity of spleen tyrosine kinase (SYK) and phosphatidylinositol 3-kinase delta (PI3Kδ) but was unaffected by inhibitors of Bruton’s tyrosine kinase (BTK).
CLL cells can internalize and present antigen from anti-IgM beads. This capacity of CLL cells may be particularly important for recruitment of T-cell help in vivo in response to particulate antigens.
During the past two decades, tremendous progress has been made in the dendrimer-based delivery of therapeutic molecules including, for instance, small molecules, macromolecules, and genes. This review deals with recent successes in the development of promising biocompatible phosphorus dendrimers, a specific type of dendrimer, to deliver genes to treat cancers.
[Names] => Serge Mignani ... Jean-Pierre Majoral [Doi] => 10.37349/etat.2022.00071 [Published] => February 25, 2022 [Viewed] => 1403 [Downloaded] => 44 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00071 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 51 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:50–61 [Recommend] => 0 [Keywords] => Phosphorus dendrimers, gene delivery, cancer therapeutics [DetailTitle] => Gene Delivery Approach to Fight Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/51 [Id] => 100271 [ris] => https://www.explorationpub.com/uploads/Article/A100271/f591d437baadec9c990d00445bad3aa9.ris [bib] => https://www.explorationpub.com/uploads/Article/A100271/57c25100740e2133d22f387cb893b71e.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Mignani S, Shi X, Bryszewska M, Shcharbin D, Majoral JP. Engineered phosphorus dendrimers as powerful non-viral nanoplatforms for gene delivery: a great hope for the future of cancer therapeutics. Explor Target Antitumor Ther. 2022;3:50–61. https://doi.org/10.37349/etat.2022.00071 [Jindex] => 0 [CName] => SergeMignani,XiangyangShi,Jean-PierreMajoral, [CEmail] => serge.mignani@staff.uma.pt,xshi@dhu.edu.cn,majoral@lcc-toulouse.fr, [Ris_Time] => 2022-02-25 06:39:29 [Bib_Time] => 2022-02-25 06:39:29 [KeysWordContens] => Engineered phosphorus dendrimers as powerful non-viral nanoplatforms for gene delivery: a great hope for the future of cancer therapeutics, Phosphorus dendrimers, gene delivery, cancer therapeutics, During the past two decades, tremendous progress has been made in the dendrimer-based delivery of therapeutic molecules including, for instance, small molecules, macromolecules, and genes. This review deals with recent successes in the development of promising biocompatible phosphorus dendrimers, a specific type of dendrimer, to deliver genes to treat cancers. ,Serge Mignani ... Jean-Pierre Majoral [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [71] => Array ( [ArticleId] => 272 [Create_Time] => 2022-02-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202203/20220301022515.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100272/100272.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100272/100272.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100272/100272_cover.png [JournalsId] => 4 [Title] => Targeting the two-pore channel 2 in cancer progression and metastasis [Abstract] => The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. [AbstractComplete] =>The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions of TPC2 and a discussion of its potential as a target for therapeutic intervention, including a summary of clinical trials examining the TPC2 inhibitors, naringenin, tetrandrine, and verapamil for the treatment of various cancers is provided.
[Names] => Kathryn A. Skelding ... Lisa F. Lincz [Doi] => 10.37349/etat.2022.00072 [Published] => February 28, 2022 [Viewed] => 2019 [Downloaded] => 51 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00072 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 35 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:62–89 [Recommend] => 0 [Keywords] => Two-pore channel 2, TPCN2, tetrandrine, naringenin, cancer, anti-cancer drugs, verapamil [DetailTitle] => Calcium Signaling Apparatus in Cancers [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/35 [Id] => 100272 [ris] => https://www.explorationpub.com/uploads/Article/A100272/2f2590d8ed96b5df888982a3f0488c27.ris [bib] => https://www.explorationpub.com/uploads/Article/A100272/aa27b472d930142047d5bb949ce03957.bib [ens] => [Cited] => 6 [Cited_Time] => 2024-04-27 [CitethisArticle] => Skelding KA, Barry DL, Theron DZ, Lincz LF. Targeting the two-pore channel 2 in cancer progression and metastasis. Explor Target Antitumor Ther. 2022;3:62–89. https://doi.org/10.37349/etat.2022.00072 [Jindex] => 0 [CName] => Kathryn A.Skelding, [CEmail] => Kathryn.Skelding@newcastle.edu.au, [Ris_Time] => 2022-02-25 11:18:34 [Bib_Time] => 2022-02-25 11:18:34 [KeysWordContens] => Targeting the two-pore channel 2 in cancer progression and metastasis, Two-pore channel 2, TPCN2, tetrandrine, naringenin, cancer, anti-cancer drugs, verapamil, The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions of TPC2 and a discussion of its potential as a target for therapeutic intervention, including a summary of clinical trials examining the TPC2 inhibitors, naringenin, tetrandrine, and verapamil for the treatment of various cancers is provided. ,Kathryn A. Skelding ... Lisa F. Lincz [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [72] => Array ( [ArticleId] => 273 [Create_Time] => 2022-02-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202203/20220301004511.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100273/100273.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100273/100273.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100273/100273_cover.png [JournalsId] => 4 [Title] => Liver venous deprivation for resection of advanced hilar cholangiocarcinoma—a case report and review of the literature [Abstract] => Hilar cholangiocarcinoma is a rare primary malignancy associated with a dismal prognosis. Currently, complete extended right or left-sided hepatectomy is the primary curative therapy. Achieving a ne [AbstractComplete] =>Hilar cholangiocarcinoma is a rare primary malignancy associated with a dismal prognosis. Currently, complete extended right or left-sided hepatectomy is the primary curative therapy. Achieving a negative resection margin is associated with long-term survival and better quality of life, while post-hepatectomy liver failure (PHLF) due to insufficient liver remnant remains the most dreaded complication with a negative effect on overall survival. Precise preoperative management with sufficient future remnant liver (FRL) volume is the key to achieving good results in the treatment of bile duct carcinoma. To present a case report and a literature review for preoperative FRL optimization prior to major hepatectomies for hilar cholangiocarcinoma. Improvement of postoperative outcomes after extended liver resections in the case of hilar cholangiocarcinoma. A 62-year-old Caucasian woman with Lynch syndrome presented to our department with a hilar cholangiocarcinoma Bismuth type IIIa. The patient had an insufficient future liver volume for extended liver resection. She underwent preoperative preconditioning using a liver venous deprivation (LVD) and underwent two weeks later a right trisectorectomy without any interventional complications. Liver function remained stable postoperatively. The patient was discharged on the 20th postoperative day without major surgical post-operative complications or the need for readmission. LVD is a technically feasible, safe, and effective procedure to increase the FRL in a short period of time with low intra and post-operative complications and therefore improving the survival of patients with hilar cholangiocarcinoma.
[Names] => Radoslava Stoyanova ... Alexander Klaus [Doi] => 10.37349/etat.2022.00073 [Published] => February 28, 2022 [Viewed] => 1344 [Downloaded] => 51 [Subject] => Case Report [Year] => 2022 [CiteUrl] => https://api.crossref.org/works//10.37349/etat.2022.00073 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 41 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:90–96 [Recommend] => 0 [Keywords] => Hilar cholangiocarcinoma, Klatskin, liver venous deprivation, portal vein embolization, future liver remnant, extended hepatectomy [DetailTitle] => Precision Medicine for Cholangiocarcinoma [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/41 [Id] => 100273 [ris] => https://www.explorationpub.com/uploads/Article/A100273/5a6338468feb9ca280a67a5044951d0a.ris [bib] => https://www.explorationpub.com/uploads/Article/A100273/c61d49d0b0b3550491d66d8886d91fae.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Stoyanova R, Kopf H, Schima W, Matzek WK, Klaus A. Liver venous deprivation for resection of advanced hilar cholangiocarcinoma—a case report and review of the literature. Explor Target Antitumor Ther. 2022;3:90–6. https://doi.org/10.37349/etat.2022.00073 [Jindex] => 0 [CName] => RadoslavaStoyanova, [CEmail] => Radoslava.Stoyanova@bhs.at, [Ris_Time] => 2022-02-25 05:29:58 [Bib_Time] => 2022-02-25 05:29:58 [KeysWordContens] => Liver venous deprivation for resection of advanced hilar cholangiocarcinoma—a case report and review of the literature, Hilar cholangiocarcinoma, Klatskin, liver venous deprivation, portal vein embolization, future liver remnant, extended hepatectomy, Hilar cholangiocarcinoma is a rare primary malignancy associated with a dismal prognosis. Currently, complete extended right or left-sided hepatectomy is the primary curative therapy. Achieving a negative resection margin is associated with long-term survival and better quality of life, while post-hepatectomy liver failure (PHLF) due to insufficient liver remnant remains the most dreaded complication with a negative effect on overall survival. Precise preoperative management with sufficient future remnant liver (FRL) volume is the key to achieving good results in the treatment of bile duct carcinoma. To present a case report and a literature review for preoperative FRL optimization prior to major hepatectomies for hilar cholangiocarcinoma. Improvement of postoperative outcomes after extended liver resections in the case of hilar cholangiocarcinoma. A 62-year-old Caucasian woman with Lynch syndrome presented to our department with a hilar cholangiocarcinoma Bismuth type IIIa. The patient had an insufficient future liver volume for extended liver resection. She underwent preoperative preconditioning using a liver venous deprivation (LVD) and underwent two weeks later a right trisectorectomy without any interventional complications. Liver function remained stable postoperatively. The patient was discharged on the 20th postoperative day without major surgical post-operative complications or the need for readmission. LVD is a technically feasible, safe, and effective procedure to increase the FRL in a short period of time with low intra and post-operative complications and therefore improving the survival of patients with hilar cholangiocarcinoma. ,Radoslava Stoyanova ... Alexander Klaus [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [73] => Array ( [ArticleId] => 274 [Create_Time] => 2022-02-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202203/20220301031455.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100274/100274.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100274/100274.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100274/100274_cover.png [JournalsId] => 4 [Title] => Collateral-resistance to estrogen and HER-activated growth is associated with modified AKT, ERα, and cell-cycle signaling in a breast cancer model [Abstract] => Aim: A model of progressively endocrine-resistant breast cancer was investigated to identify changes that can occur in signaling pathways after endocrine manipulation. Methods: The MCF7 breas [AbstractComplete] =>A model of progressively endocrine-resistant breast cancer was investigated to identify changes that can occur in signaling pathways after endocrine manipulation.
The MCF7 breast cancer model is sensitive to estrogens and anti-estrogens while variant lines previously derived from wild-type MCF7 are either relatively 17β-estradiol (E2 )-insensitive (LCC1) or fully resistant to estrogen and anti-estrogens (LCC9).
In LCC1 and LCC9 cell lines, loss of estrogen sensitivity was accompanied by loss of growth response to transforming growth factor alpha (TGFα), heregulin-beta and pertuzumab. LCC1 and LCC9 cells had enhanced AKT phosphorylation relative to MCF7 which was reflected in downstream activation of phospho-mechanistic target of rapamycin (mTOR), phospho-S6, and phospho-estrogen receptor alpha Ser167 [ERα(Ser167)]. Both AKT2 and AKT3 were phosphorylated in the resistant cell lines, but small interfering RNA (siRNA) knockdown suggested that all three AKT isoforms contributed to growth response. ERα(Ser118) phosphorylation was increased by E2 and TGFα in MCF7, by E2 only in LCC1, but by neither in LCC9 cells. Multiple alterations in E2-mediated cell cycle control were identified in the endocrine-resistant cell lines including increased expression of MYC, cyclin A1, cyclin D1, cyclin-dependent kinase 1 (CDK1), CDK2, and hyperphosphorylated retinoblastoma protein (ppRb), whereas p21 and p27 were reduced. Estrogen modulated expression of these regulators in MCF7 and LCC1 cells but not in LCC9 cells. Seliciclib inhibited CDK2 activation in MCF7 cells but not in resistant variants; in all lines, it reduced ppRb, increased p53 associated responses including p21, p53 up-regulated modulator of apoptosis (PUMA), and p53 apoptosis-inducing protein 1 (p53AIP1), inhibited growth, and produced G2/M block and apoptosis.
Multiple changes occur with progression of endocrine resistance in this model with AKT activation contributing to E2 insensitivity and loss of ERα(Ser118) phosphorylation being associated with full resistance. Cell cycle regulation is modified in endocrine-resistant breast cancer cells, and seliciclib is effective in both endocrine-sensitive and resistant diseases.
Messenger RNA (mRNA) has recently made important progress in clinical implementation, offering a promising therapeutic option for infectious disease and cancer. However, the nature of mRNA molecules rendered them poorly bioavailable and unstable in vivo, impeding their further clinical application. Therefore, safe and efficient delivery of mRNA therapeutics to the target site is crucial for their successful translation into the clinical setting. Various vectors have been explored for mRNA delivery. Among them, polyesters and their analogs, a family of biodegradable polymers, have exhibited great potential for mRNA delivery. In this short review, the authors briefly introduce mRNA therapeutics, their therapeutic applications and delivery challenges. The authors then presented the typical examples of polyester materials for mRNA delivery to highlight the current progress and discuss the challenges for the rational design of polyester based mRNA delivery vectors. The authors hope to provide a new insight for the design of biodegradable vectors for nucleic acids delivery, thereby promoting their further clinic translation.
[Names] => Wang Chen ... Dandan Zhu [Doi] => 10.37349/etat.2022.00075 [Published] => March 11, 2022 [Viewed] => 2001 [Downloaded] => 116 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00075 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 51 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:117–127 [Recommend] => 0 [Keywords] => mRNA, mRNA delivery, polyester, poly(β-amino ester), gene therapy [DetailTitle] => Gene Delivery Approach to Fight Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/51 [Id] => 100275 [ris] => https://www.explorationpub.com/uploads/Article/A100275/8a26002ebcfb4c52624a7982961ac13b.ris [bib] => https://www.explorationpub.com/uploads/Article/A100275/51850597908588b303a591aa3422b66b.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-27 [CitethisArticle] => Chen W, Ma Y, Liu X, Zhu D. Polyester materials for mRNA delivery. Explor Target Antitumor Ther. 2022;3:117–27. https://doi.org/10.37349/etat.2022.00075 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-03-11 09:48:40 [Bib_Time] => 2022-03-11 09:48:40 [KeysWordContens] => Polyester materials for mRNA delivery, mRNA, mRNA delivery, polyester, poly(β-amino ester), gene therapy, Messenger RNA (mRNA) has recently made important progress in clinical implementation, offering a promising therapeutic option for infectious disease and cancer. However, the nature of mRNA molecules rendered them poorly bioavailable and unstable in vivo, impeding their further clinical application. Therefore, safe and efficient delivery of mRNA therapeutics to the target site is crucial for their successful translation into the clinical setting. Various vectors have been explored for mRNA delivery. Among them, polyesters and their analogs, a family of biodegradable polymers, have exhibited great potential for mRNA delivery. In this short review, the authors briefly introduce mRNA therapeutics, their therapeutic applications and delivery challenges. The authors then presented the typical examples of polyester materials for mRNA delivery to highlight the current progress and discuss the challenges for the rational design of polyester based mRNA delivery vectors. The authors hope to provide a new insight for the design of biodegradable vectors for nucleic acids delivery, thereby promoting their further clinic translation. ,Wang Chen ... Dandan Zhu [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [75] => Array ( [ArticleId] => 287 [Create_Time] => 2022-04-02 [zipUrl] => https://www.explorationpub.com/uploads/zip/202204/20220402085655.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100276/100276.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100276/100276.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100276/100276_cover.png [JournalsId] => 4 [Title] => Yeast as a tool to decipher the molecular mechanisms underlying the functions of Bcl-2 family [Abstract] => The budding yeastThe budding yeast Saccharomyces cerevisiae, a favorite model in biology, does not contain any protein of the Bcl-2 family. From initial experiments with two-hybrid systems to the heterologous expression of human Bcl-2 family members, and the characterization of several forms of yeast programmed cell death, it has however always been a powerful tool to gain information on the mechanisms of apoptosis in general and on Bcl-2 family in particular. This is a short survey of 25 years of experiments that have provided, and at times initiated, insights into the molecular mechanisms underlying the function of Bcl-2 family members.
[Names] => Stéphen Manon [Doi] => 10.37349/etat.2022.00076 [Published] => April 02, 2022 [Viewed] => 1678 [Downloaded] => 43 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00076 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 52 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:128–148 [Recommend] => 0 [Keywords] => Apoptosis, Bcl-2 family, programmed cell death, yeast, heterologous expression [DetailTitle] => The Role of Bcl-2 Family Proteins in Cancer Progression and Their Relevance to Cancer Therapy [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/52 [Id] => 100276 [ris] => https://www.explorationpub.com/uploads/Article/A100276/8562fb063c32aeb62b8d3cc14c1d59ac.ris [bib] => https://www.explorationpub.com/uploads/Article/A100276/9168cdc28671e49a50fe6370752bd01d.bib [ens] => [Cited] => 5 [Cited_Time] => 2024-04-27 [CitethisArticle] => Manon S. Yeast as a tool to decipher the molecular mechanisms underlying the functions of Bcl-2 family. Explor Target Antitumor Ther. 2022;3:128–48. https://doi.org/10.37349/etat.2022.00076 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-04-02 08:58:11 [Bib_Time] => 2022-04-02 08:58:11 [KeysWordContens] => Yeast as a tool to decipher the molecular mechanisms underlying the functions of Bcl-2 family, Apoptosis, Bcl-2 family, programmed cell death, yeast, heterologous expression, The budding yeast Saccharomyces cerevisiae, a favorite model in biology, does not contain any protein of the Bcl-2 family. From initial experiments with two-hybrid systems to the heterologous expression of human Bcl-2 family members, and the characterization of several forms of yeast programmed cell death, it has however always been a powerful tool to gain information on the mechanisms of apoptosis in general and on Bcl-2 family in particular. This is a short survey of 25 years of experiments that have provided, and at times initiated, insights into the molecular mechanisms underlying the function of Bcl-2 family members. ,Stéphen Manon [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [76] => Array ( [ArticleId] => 289 [Create_Time] => 2022-04-19 [zipUrl] => https://www.explorationpub.com/uploads/zip/202204/20220418055134.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100277/100277.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100277/100277.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100277/100277_cover.png [JournalsId] => 4 [Title] => Advancing antibody-drug conjugates in gynecological malignancies: myth or reality? [Abstract] => Antibody-drug conjugates (ADCs) represent a new class of therapeutic agents designed to target specific antigens on tumor cells, combining the specificity of monoclonal antibodies to the cytotoxicit [AbstractComplete] =>Antibody-drug conjugates (ADCs) represent a new class of therapeutic agents designed to target specific antigens on tumor cells, combining the specificity of monoclonal antibodies to the cytotoxicity of classic chemotherapy agents. These drugs have been extensively studied both in solid and hematologic malignancies, leading to substantial improvement in the therapeutic landscape for several tumors. Despite no ADC have been yet approved for the treatment of gynecological malignancies, some agents have shown promising results and might have the potential to become part of the standard of care. Among them, mirvetuximab soravtansine has shown activity in platinum-resistant ovarian cancer with high folate-α receptor expression, as a single agent and in combination. Tisotumab vedotin is active in patients with pre-treated cervical cancer, and further investigation is ongoing. The purpose of this review is to summarize the structural and functional characteristics of ADCs and analyze the most recent and promising data regarding the clinical development of ADCs in gynecological malignancies. The available data on the efficacy of the more studied ADCs in ovarian, endometrial, and cervical cancers will be discussed along with toxicities of special interest, the mechanisms of resistance, and future possible drugs combination.
[Names] => Marta Nerone ... Ilaria Colombo [Doi] => 10.37349/etat.2022.00077 [Published] => April 19, 2022 [Viewed] => 3509 [Downloaded] => 102 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00077 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 45 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:149–171 [Recommend] => 1 [Keywords] => Antibody-drug conjugates, gynecological malignancies, ovarian cancer, endometrial cancer, cervical cancer [DetailTitle] => Antibody-Drug Conjugates [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/45 [Id] => 100277 [ris] => https://www.explorationpub.com/uploads/Article/A100277/dec68b29b5ff22204d326930ea9d6e1c.ris [bib] => https://www.explorationpub.com/uploads/Article/A100277/a0d6d6d60954494ee4136ef3801803e9.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-27 [CitethisArticle] => Nerone M, Del Grande M, Sessa C, Colombo I. Advancing antibody-drug conjugates in gynecological malignancies: myth or reality? Explor Target Antitumor Ther. 2022;3:149–71. https://doi.org/10.37349/etat.2022.00077 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-04-15 02:18:09 [Bib_Time] => 2022-04-15 02:24:03 [KeysWordContens] => Advancing antibody-drug conjugates in gynecological malignancies: myth or reality?, Antibody-drug conjugates, gynecological malignancies, ovarian cancer, endometrial cancer, cervical cancer, Antibody-drug conjugates (ADCs) represent a new class of therapeutic agents designed to target specific antigens on tumor cells, combining the specificity of monoclonal antibodies to the cytotoxicity of classic chemotherapy agents. These drugs have been extensively studied both in solid and hematologic malignancies, leading to substantial improvement in the therapeutic landscape for several tumors. Despite no ADC have been yet approved for the treatment of gynecological malignancies, some agents have shown promising results and might have the potential to become part of the standard of care. Among them, mirvetuximab soravtansine has shown activity in platinum-resistant ovarian cancer with high folate-α receptor expression, as a single agent and in combination. Tisotumab vedotin is active in patients with pre-treated cervical cancer, and further investigation is ongoing. The purpose of this review is to summarize the structural and functional characteristics of ADCs and analyze the most recent and promising data regarding the clinical development of ADCs in gynecological malignancies. The available data on the efficacy of the more studied ADCs in ovarian, endometrial, and cervical cancers will be discussed along with toxicities of special interest, the mechanisms of resistance, and future possible drugs combination. ,Marta Nerone ... Ilaria Colombo [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [77] => Array ( [ArticleId] => 292 [Create_Time] => 2022-04-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202204/20220424074358.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100278/100278.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100278/100278.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100278/100278_cover.png [JournalsId] => 4 [Title] => Role of PI3K/Akt/mTOR pathway in mediating endocrine resistance: concept to clinic [Abstract] => The majority of breast cancers express the estrogen receptor (ER) and for this group of patients, endocrine therapy is the cornerstone of systemic treatment. However, drug resistance is common and a [AbstractComplete] =>The majority of breast cancers express the estrogen receptor (ER) and for this group of patients, endocrine therapy is the cornerstone of systemic treatment. However, drug resistance is common and a focus for breast cancer preclinical and clinical research. Over the past 2 decades, the PI3K/Akt/mTOR axis has emerged as an important driver of treatment failure, and inhibitors of mTOR and PI3K are now licensed for the treatment of women with advanced ER-positive breast cancer who have relapsed on first-line hormonal therapy. This review presents the preclinical and clinical data that led to this new treatment paradigm and discusses future directions.
[Names] => Aglaia Skolariki ... Simon Lord [Doi] => 10.37349/etat.2022.00078 [Published] => April 24, 2022 [Viewed] => 2305 [Downloaded] => 73 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00078 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 48 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:172–199 [Recommend] => 0 [Keywords] => Breast cancer, endocrine therapy, PI3K/Akt/mTOR pathway [DetailTitle] => Endocrine Resistant Breast Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/48 [Id] => 100278 [ris] => https://www.explorationpub.com/uploads/Article/A100278/d3316d7ea41f97ba67506f9499b1264f.ris [bib] => https://www.explorationpub.com/uploads/Article/A100278/148b933642f106f6fb953087cb23ef74.bib [ens] => [Cited] => 6 [Cited_Time] => 2024-04-27 [CitethisArticle] => Skolariki A, D’Costa J, Little M, Lord S. Role of PI3K/Akt/mTOR pathway in mediating endocrine resistance: concept to clinic. Explor Target Antitumor Ther. 2022;3:172–99. https://doi.org/10.37349/etat.2022.00078 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-04-24 07:46:21 [Bib_Time] => 2022-04-24 07:46:21 [KeysWordContens] => Role of PI3K/Akt/mTOR pathway in mediating endocrine resistance: concept to clinic, Breast cancer, endocrine therapy, PI3K/Akt/mTOR pathway, The majority of breast cancers express the estrogen receptor (ER) and for this group of patients, endocrine therapy is the cornerstone of systemic treatment. However, drug resistance is common and a focus for breast cancer preclinical and clinical research. Over the past 2 decades, the PI3K/Akt/mTOR axis has emerged as an important driver of treatment failure, and inhibitors of mTOR and PI3K are now licensed for the treatment of women with advanced ER-positive breast cancer who have relapsed on first-line hormonal therapy. This review presents the preclinical and clinical data that led to this new treatment paradigm and discusses future directions. ,Aglaia Skolariki ... Simon Lord [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [78] => Array ( [ArticleId] => 297 [Create_Time] => 2022-04-26 [zipUrl] => https://www.explorationpub.com/uploads/zip/202204/20220426022535.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100279/100279.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100279/100279.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100279/100279_cover.png [JournalsId] => 4 [Title] => Genomic alterations in cholangiocarcinoma: clinical significance and relevance to therapy [Abstract] => Improving the survival of patients with cholangiocarcinoma (CCA) has long proved challenging, although the treatment of this disease nowadays is on advancement. The historical invariability of survi [AbstractComplete] =>Improving the survival of patients with cholangiocarcinoma (CCA) has long proved challenging, although the treatment of this disease nowadays is on advancement. The historical invariability of survival outcomes and the limited number of agents known to be effective in the treatment of this disease has increased the number of studies designed to identify genetic targetable hits that can be efficacious for novel therapies. In this respect, the increasing feasibility of molecular profiling starting either from tumor tissue or circulating cell-free DNA (cfDNA) has led to an increased understanding of CCA biology. Intrahepatic CCA (iCCA) and extrahepatic CCA (eCCA) display different and typical patterns of actionable genomic alterations, which offer opportunity for therapeutic intervention. This review article will summarize the current knowledge on the genomic alterations of iCCA and eCCA, provide information on the main technologies for genomic profiling using either tumor tissue or cfDNA, and briefly discuss the main clinical trials with targeted agents in this disease.
[Names] => Marianeve Carotenuto ... Nicola Normanno [Doi] => 10.37349/etat.2022.00079 [Published] => April 26, 2022 [Viewed] => 2656 [Downloaded] => 59 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00079 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 41 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:200–223 [Recommend] => 1 [Keywords] => Cholangiocarcinoma, molecular profiling, genomic alterations, targeted therapy, circulating tumor DNA [DetailTitle] => Precision Medicine for Cholangiocarcinoma [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/41 [Id] => 100279 [ris] => https://www.explorationpub.com/uploads/Article/A100279/c058a3963d84cab475b4665ed38d59f1.ris [bib] => https://www.explorationpub.com/uploads/Article/A100279/90dd646fa30adc06219d89e7251f4dd4.bib [ens] => [Cited] => 8 [Cited_Time] => 2024-04-27 [CitethisArticle] => Carotenuto M, Sacco A, Forgione L, Normanno N. Genomic alterations in cholangiocarcinoma: clinical significance and relevance to therapy. Explor Target Antitumor Ther. 2022;3:200–23. https://doi.org/10.37349/etat.2022.00079 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-04-24 02:47:03 [Bib_Time] => 2022-04-24 02:47:03 [KeysWordContens] => Genomic alterations in cholangiocarcinoma: clinical significance and relevance to therapy, Cholangiocarcinoma, molecular profiling, genomic alterations, targeted therapy, circulating tumor DNA, Improving the survival of patients with cholangiocarcinoma (CCA) has long proved challenging, although the treatment of this disease nowadays is on advancement. The historical invariability of survival outcomes and the limited number of agents known to be effective in the treatment of this disease has increased the number of studies designed to identify genetic targetable hits that can be efficacious for novel therapies. In this respect, the increasing feasibility of molecular profiling starting either from tumor tissue or circulating cell-free DNA (cfDNA) has led to an increased understanding of CCA biology. Intrahepatic CCA (iCCA) and extrahepatic CCA (eCCA) display different and typical patterns of actionable genomic alterations, which offer opportunity for therapeutic intervention. This review article will summarize the current knowledge on the genomic alterations of iCCA and eCCA, provide information on the main technologies for genomic profiling using either tumor tissue or cfDNA, and briefly discuss the main clinical trials with targeted agents in this disease. ,Marianeve Carotenuto ... Nicola Normanno [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [79] => Array ( [ArticleId] => 299 [Create_Time] => 2022-04-26 [zipUrl] => https://www.explorationpub.com/uploads/zip/202204/20220427080358.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100280/100280.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100280/100280.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100280/100280_cover.png [JournalsId] => 4 [Title] => The importance of targeting signalling mechanisms of the SLC39A family of zinc transporters to inhibit endocrine resistant breast cancer [Abstract] => Aim: Zinc is a key secondary messenger that can regulate multiple signalling pathways within cancer cells, thus its levels need to be strictly controlled. The Zrt, Irt-like protein (ZIP, SLC39A) [AbstractComplete] =>Zinc is a key secondary messenger that can regulate multiple signalling pathways within cancer cells, thus its levels need to be strictly controlled. The Zrt, Irt-like protein (ZIP, SLC39A) family of zinc transporters increase cytosolic zinc from either extracellular or intracellular stores. This study examines the relevance of zinc transporters ZIP7 and ZIP6 as therapeutic targets in tamoxifen resistant (TAMR) breast cancer.
A series of in vitro assays, including immunohistochemistry, immunofluorescence, flow cytometry, and western blotting were used to evaluate levels and activity of ZIP7 and ZIP6 in models of TAMR and sensitive (MCF-7) breast cancer. Analyses of these transporters in the clinical setting were performed using publicly available online resources: Gene Expression Profiling Interactive Analysis (GEPIA)2 and Kaplan-Meier Plotter (KmPlot).
Both
TAMR cells displayed increased activity of both ZIP7 and ZIP6 transporters compared to anti-hormone responsive cells, suggesting their potential as novel therapeutic targets following development of resistant disease.
Endocrine resistant breast cancer metastasis continues to serve as a significant clinical challenge with high morbidity and mortality for patients. As the number of breast cancer cases continues to rise, the rate of brain metastasis has also increased. For single lesions or a large symptomatic lesion with other smaller lesions, surgical resection is a viable option in non-eloquent regions. Stereotactic radiosurgery is a great option for post-operative therapy or for 10 or fewer small lesions (< 3 cm in size). Whole-brain radiation can be used sparingly for large tumor burdens but should encompass hippocampus sparing techniques. Chemotherapy options have remained relatively limited due to decreased permeability of the blood-brain barrier. Emerging monoclonal antibody treatments have offered initial promise, especially for endocrine resistant breast cancer metastasis.
[Names] => Matthew Willman ... Brandon Lucke-Wold [Doi] => 10.37349/etat.2022.00081 [Published] => April 26, 2022 [Viewed] => 1540 [Downloaded] => 39 [Subject] => Perspective [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00081 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 48 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:240–251 [Recommend] => 0 [Keywords] => Endocrine resistant breast cancer, metastasis, brain oncology, emerging therapeutics [DetailTitle] => Endocrine Resistant Breast Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/48 [Id] => 100281 [ris] => https://www.explorationpub.com/uploads/Article/A100281/61358cc0df0f70f5165492dad22b6a83.ris [bib] => https://www.explorationpub.com/uploads/Article/A100281/5c6dcdc48bdc32b66e01be13e3162fa5.bib [ens] => [Cited] => 7 [Cited_Time] => 2024-04-27 [CitethisArticle] => Willman M, Willman J, Lucke-Wold B. Endocrine resistant breast cancer: brain metastasis. Explor Target Antitumor Ther. 2022;3:240–51. https://doi.org/10.37349/etat.2022.00081 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-04-27 03:10:01 [Bib_Time] => 2022-04-27 03:10:01 [KeysWordContens] => Endocrine resistant breast cancer: brain metastasis, Endocrine resistant breast cancer, metastasis, brain oncology, emerging therapeutics, Endocrine resistant breast cancer metastasis continues to serve as a significant clinical challenge with high morbidity and mortality for patients. As the number of breast cancer cases continues to rise, the rate of brain metastasis has also increased. For single lesions or a large symptomatic lesion with other smaller lesions, surgical resection is a viable option in non-eloquent regions. Stereotactic radiosurgery is a great option for post-operative therapy or for 10 or fewer small lesions (< 3 cm in size). Whole-brain radiation can be used sparingly for large tumor burdens but should encompass hippocampus sparing techniques. Chemotherapy options have remained relatively limited due to decreased permeability of the blood-brain barrier. Emerging monoclonal antibody treatments have offered initial promise, especially for endocrine resistant breast cancer metastasis. ,Matthew Willman ... Brandon Lucke-Wold [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [81] => Array ( [ArticleId] => 303 [Create_Time] => 2022-04-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202205/20220511061445.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100282/100282.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100282/100282.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100282/100282_cover.png [JournalsId] => 4 [Title] => Antibody-drug conjugates: beyond current approvals and potential future strategies [Abstract] => The recent approvals for antibody-drug conjugates (ADCs) in multiple malignancies in recent years have fuelled the ongoing development of this class of drugs. These novel agents combine the benefits [AbstractComplete] =>The recent approvals for antibody-drug conjugates (ADCs) in multiple malignancies in recent years have fuelled the ongoing development of this class of drugs. These novel agents combine the benefits of high specific targeting of oncogenic cell surface antigens with the additional cell kill from high potency cytotoxic payloads, thus achieving wider therapeutic windows. This review will summarise the clinical activity of ADCs in tumour types not covered elsewhere in this issue, such as gastrointestinal (GI) and genitourinary (GU) cancers and glioblastoma (GBM). In addition to the ongoing clinical testing of existing ADCs, there is substantial preclinical and early phase testing of newer ADCs or ADC incorporating strategies. This review will provide selected insights into such future development, focusing on the development of novel ADCs against new antigen targets in the tumour microenvironment (TME) and combination of ADCs with immuno-oncology (IO) agents.
[Names] => Siddharth Menon ... Hui K. Gan [Doi] => 10.37349/etat.2022.00082 [Published] => April 28, 2022 [Viewed] => 4786 [Downloaded] => 206 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00082 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 45 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:252–277 [Recommend] => 0 [Keywords] => Antibody-drug conjugates, immunotherapy, tumour microenvironment [DetailTitle] => Antibody-Drug Conjugates [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/45 [Id] => 100282 [ris] => https://www.explorationpub.com/uploads/Article/A100282/0d4789449f6b320ebe90cdd98ea44d84.ris [bib] => https://www.explorationpub.com/uploads/Article/A100282/7c9341d591231dc44b8a8843a93412b1.bib [ens] => [Cited] => 10 [Cited_Time] => 2024-04-27 [CitethisArticle] => Menon S, Parakh S, Scott AM, Gan HK. Antibody-drug conjugates: beyond current approvals and potential future strategies. Explor Target Antitumor Ther. 2022;3:252–77. https://doi.org/10.37349/etat.2022.00082 [Jindex] => 0 [CName] => SiddharthMenon, [CEmail] => siddharth.menon@onjcri.org.au, [Ris_Time] => 2022-04-25 08:50:33 [Bib_Time] => 2022-04-25 08:50:33 [KeysWordContens] => Antibody-drug conjugates: beyond current approvals and potential future strategies, Antibody-drug conjugates, immunotherapy, tumour microenvironment, The recent approvals for antibody-drug conjugates (ADCs) in multiple malignancies in recent years have fuelled the ongoing development of this class of drugs. These novel agents combine the benefits of high specific targeting of oncogenic cell surface antigens with the additional cell kill from high potency cytotoxic payloads, thus achieving wider therapeutic windows. This review will summarise the clinical activity of ADCs in tumour types not covered elsewhere in this issue, such as gastrointestinal (GI) and genitourinary (GU) cancers and glioblastoma (GBM). In addition to the ongoing clinical testing of existing ADCs, there is substantial preclinical and early phase testing of newer ADCs or ADC incorporating strategies. This review will provide selected insights into such future development, focusing on the development of novel ADCs against new antigen targets in the tumour microenvironment (TME) and combination of ADCs with immuno-oncology (IO) agents. ,Siddharth Menon ... Hui K. Gan [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [82] => Array ( [ArticleId] => 314 [Create_Time] => 2022-05-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202205/20220524021515.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100283/100283.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100283/100283.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100283/100283_cover.png [JournalsId] => 4 [Title] => Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it [Abstract] => The antiapoptotic B cell lymphoma-2 (Bcl-2) family members are apical regulators of the intrinsic pathway of apoptosis that orchestrate mitochondrial outer membrane permeabilization (MOMP) through i [AbstractComplete] =>The antiapoptotic B cell lymphoma-2 (Bcl-2) family members are apical regulators of the intrinsic pathway of apoptosis that orchestrate mitochondrial outer membrane permeabilization (MOMP) through interactions with their proapoptotic counterparts. Overexpression of antiapoptotic Bcl-2 family proteins has been linked to therapy resistance and poor prognosis in diverse cancers. Among the antiapoptotic Bcl-2 family members, predominant overexpression of the prosurvival myeloid cell leukemia-1 (Mcl-1) has been reported in a myriad of hematological malignancies and solid tumors, contributing to therapy resistance and poor outcomes, thus making it a potential druggable target. The unique structure of Mcl-1 and its complex regulatory mechanism makes it an adaptive prosurvival switch that ensures tumor cell survival despite therapeutic intervention. This review focusses on diverse mechanisms adopted by tumor cells to maintain sustained elevated levels of Mcl-1 and how high Mcl-1 levels contribute to resistance in conventional as well as targeted therapies. Moreover, recent developments in the Mcl-1-targeted therapeutics and the underlying challenges and considerations in designing novel Mcl-1 inhibitors are also discussed.
[Names] => Prasad Sulkshane, Tanuja Teni [Doi] => 10.37349/etat.2022.00083 [Published] => May 24, 2022 [Viewed] => 1735 [Downloaded] => 42 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00083 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 52 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:278–296 [Recommend] => 0 [Keywords] => Myeloid cell leukemia-1, B cell lymphoma-2, mitochondrial outer membrane permeabilization, Bcl-2 homology 3 mimetic, therapy resistance, myeloid cell leukemia-1 inhibitor [DetailTitle] => The Role of Bcl-2 Family Proteins in Cancer Progression and Their Relevance to Cancer Therapy [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/52 [Id] => 100283 [ris] => https://www.explorationpub.com/uploads/Article/A100283/69e13899f6f2811dd410b482c42d338b.ris [bib] => https://www.explorationpub.com/uploads/Article/A100283/93f23a95ea962203a7e1cc66dd074a74.bib [ens] => [Cited] => 9 [Cited_Time] => 2024-04-27 [CitethisArticle] => Sulkshane P, Teni T. Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it. Explor Target Antitumor Ther. 2022;3:278–96. https://doi.org/10.37349/etat.2022.00083 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-05-23 05:32:18 [Bib_Time] => 2022-05-23 05:32:18 [KeysWordContens] => Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it, Myeloid cell leukemia-1, B cell lymphoma-2, mitochondrial outer membrane permeabilization, Bcl-2 homology 3 mimetic, therapy resistance, myeloid cell leukemia-1 inhibitor, The antiapoptotic B cell lymphoma-2 (Bcl-2) family members are apical regulators of the intrinsic pathway of apoptosis that orchestrate mitochondrial outer membrane permeabilization (MOMP) through interactions with their proapoptotic counterparts. Overexpression of antiapoptotic Bcl-2 family proteins has been linked to therapy resistance and poor prognosis in diverse cancers. Among the antiapoptotic Bcl-2 family members, predominant overexpression of the prosurvival myeloid cell leukemia-1 (Mcl-1) has been reported in a myriad of hematological malignancies and solid tumors, contributing to therapy resistance and poor outcomes, thus making it a potential druggable target. The unique structure of Mcl-1 and its complex regulatory mechanism makes it an adaptive prosurvival switch that ensures tumor cell survival despite therapeutic intervention. This review focusses on diverse mechanisms adopted by tumor cells to maintain sustained elevated levels of Mcl-1 and how high Mcl-1 levels contribute to resistance in conventional as well as targeted therapies. Moreover, recent developments in the Mcl-1-targeted therapeutics and the underlying challenges and considerations in designing novel Mcl-1 inhibitors are also discussed. ,Prasad Sulkshane, Tanuja Teni [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [83] => Array ( [ArticleId] => 317 [Create_Time] => 2022-06-02 [zipUrl] => https://www.explorationpub.com/uploads/zip/202206/20220602010341.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100284/100284.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100284/100284.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100284/100284_cover.png [JournalsId] => 4 [Title] => In vitro breast cancer models for studying mechanisms of resistance to endocrine therapy [Abstract] => The development of endocrine resistance is a common reason for the failure of endocrine therapies in hormone receptor-positive breast cancer. This review provides an overview of the different types [AbstractComplete] =>The development of endocrine resistance is a common reason for the failure of endocrine therapies in hormone receptor-positive breast cancer. This review provides an overview of the different types of in vitro models that have been developed as tools for studying endocrine resistance. In vitro models include cell lines that have been rendered endocrine-resistant by ex vivo treatment; cell lines with de novo resistance mechanisms, including genetic alterations; three-dimensional (3D) spheroid, co-culture, and mammosphere techniques; and patient-derived organoid models. In each case, the key discoveries, different analysis strategies that are suitable, and strengths and weaknesses are discussed. Certain recently developed methodologies that can be used to further characterize the biological changes involved in endocrine resistance are then emphasized, along with a commentary on the types of research outcomes that using these techniques can support. Finally, a discussion anticipates how these recent developments will shape future trends in the field. We hope this overview will serve as a useful resource for investigators that are interested in understanding and testing hypotheses related to mechanisms of endocrine therapy resistance.
[Names] => Gary J. Cheng ... Dean C. Singleton [Doi] => 10.37349/etat.2022.00084 [Published] => June 01, 2022 [Viewed] => 1832 [Downloaded] => 67 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00084 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 48 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:297–320 [Recommend] => 0 [Keywords] => Endocrine therapy resistance, oestrogen receptor, breast cancer, cell line models [DetailTitle] => Endocrine Resistant Breast Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/48 [Id] => 100284 [ris] => https://www.explorationpub.com/uploads/Article/A100284/71dbcd523d58bcaa92d2b60d9010d129.ris [bib] => https://www.explorationpub.com/uploads/Article/A100284/1134a0c9f2f5fb5d4abd0cdfc5a6d271.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-27 [CitethisArticle] => Cheng GJ, Leung EY, Singleton DC. In vitro breast cancer models for studying mechanisms of resistance to endocrine therapy. Explor Target Antitumor Ther. 2022;3:297–320. https://doi.org/10.37349/etat.2022.00084 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-06-02 00:50:42 [Bib_Time] => 2022-06-02 00:50:42 [KeysWordContens] => In vitro breast cancer models for studying mechanisms of resistance to endocrine therapy, Endocrine therapy resistance, oestrogen receptor, breast cancer, cell line models, The development of endocrine resistance is a common reason for the failure of endocrine therapies in hormone receptor-positive breast cancer. This review provides an overview of the different types of in vitro models that have been developed as tools for studying endocrine resistance. In vitro models include cell lines that have been rendered endocrine-resistant by ex vivo treatment; cell lines with de novo resistance mechanisms, including genetic alterations; three-dimensional (3D) spheroid, co-culture, and mammosphere techniques; and patient-derived organoid models. In each case, the key discoveries, different analysis strategies that are suitable, and strengths and weaknesses are discussed. Certain recently developed methodologies that can be used to further characterize the biological changes involved in endocrine resistance are then emphasized, along with a commentary on the types of research outcomes that using these techniques can support. Finally, a discussion anticipates how these recent developments will shape future trends in the field. We hope this overview will serve as a useful resource for investigators that are interested in understanding and testing hypotheses related to mechanisms of endocrine therapy resistance. ,Gary J. Cheng ... Dean C. Singleton [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [84] => Array ( [ArticleId] => 321 [Create_Time] => 2022-06-10 [zipUrl] => https://www.explorationpub.com/uploads/zip/202206/20220610075109.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100285/100285.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100285/100285.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100285/100285_cover.png [JournalsId] => 4 [Title] => Management of lung cancer patients during COVID-19 pandemic: dos, don’ts and don’t knows [Abstract] => Aim: During the coronavirus disease 2019 (COVID-19) pandemic two needs have overlapped: on one hand continuing to provide the best care for patients with lung cancer and preventing the spread of the [AbstractComplete] =>During the coronavirus disease 2019 (COVID-19) pandemic two needs have overlapped: on one hand continuing to provide the best care for patients with lung cancer and preventing the spread of the virus between patients and healthcare professionals on the other hand. Due to the pandemic’s unpredictable duration, physicians had to evaluate the risk/benefit ratio of anti-cancer therapeutic strategy to do the best for their patients and to protect patients themselves, as well as healthcare workers.
Systematic literature research was performed with the aim to assess the available guidelines for the management of lung cancer patients during the COVID-19 pandemic. Thirteen potentially relevant articles were selected and recommendations have been divided into three main categories: dos, don’ts and don’t knows.
All guidelines and recommendations highlighted the relevance of being able to delay, if possible and based on risk stratification, and curative interventions. The selected recommendations should be considered adaptable and flexible because they might be contextualized on the basis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection prevalence and the availability of diagnostic-therapeutic resources.
It remains of fundamental importance to discuss each diagnostic and therapeutic decision with the patient taking into account risks and benefits that might vary from case to case.
The most common breast cancer (BC) subtypes are hormone-dependent, being either estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), or both, and altogether comprise the luminal subtype. The mainstay of treatment for luminal BC is endocrine therapy (ET), which includes several agents that act either directly targeting ER action or suppressing estrogen production. Over the years, ET has proven efficacy in reducing mortality and improving clinical outcomes in metastatic and nonmetastatic BC. However, the development of ET resistance promotes cancer survival and progression and hinders the use of endocrine agents. Several mechanisms implicated in endocrine resistance have now been extensively studied. Based on the current clinical and pre-clinical data, the present article briefly reviews the well-established pathways of ET resistance and continues by focusing on the three most recently uncovered pathways, which may mediate resistance to ET, namely receptor activator of nuclear factor kappa B ligand (RANKL)/receptor activator of nuclear factor kappa B (RANK), nuclear factor kappa B (NFκB), and Notch. It additionally overviews the evidence underlying the approval of combined therapies to overcome ET resistance in BC, while highlighting the relevance of future studies focusing on putative mediators of ET resistance to uncover new therapeutic options for the disease.
[Names] => Inês Soares de Pinho ... Luís Costa [Doi] => 10.37349/etat.2022.00086 [Published] => June 20, 2022 [Viewed] => 1599 [Downloaded] => 42 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00086 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 48 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:337–361 [Recommend] => 0 [Keywords] => Breast cancer, endocrine therapy, resistance mechanisms, receptor activator of nuclear factor kappa B ligand/receptor activator of nuclear factor kappa B, nuclear factor kappa B, Notch [DetailTitle] => Endocrine Resistant Breast Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/48 [Id] => 100286 [ris] => https://www.explorationpub.com/uploads/Article/A100286/0f6e7b49d94c312be00ed4394c6fbf8b.ris [bib] => https://www.explorationpub.com/uploads/Article/A100286/97d6f8247cde4bbdc4efa383eb964015.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-26 [CitethisArticle] => de Pinho IS, Abreu C, Gomes I, Casimiro S, Pacheco TR, de Sousa RT, et al. Exploring new pathways in endocrine-resistant breast cancer. Explor Target Antitumor Ther. 2022;3:337–61. https://doi.org/10.37349/etat.2022.00086 [Jindex] => 0 [CName] => Inês Soaresde Pinho,LuísCosta, [CEmail] => inessasso.pinho@gmail.com,luiscosta.oncology@gmail.com, [Ris_Time] => 2022-06-15 08:16:04 [Bib_Time] => 2022-06-17 05:06:27 [KeysWordContens] => Exploring new pathways in endocrine-resistant breast cancer, Breast cancer, endocrine therapy, resistance mechanisms, receptor activator of nuclear factor kappa B ligand/receptor activator of nuclear factor kappa B, nuclear factor kappa B, Notch, The most common breast cancer (BC) subtypes are hormone-dependent, being either estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), or both, and altogether comprise the luminal subtype. The mainstay of treatment for luminal BC is endocrine therapy (ET), which includes several agents that act either directly targeting ER action or suppressing estrogen production. Over the years, ET has proven efficacy in reducing mortality and improving clinical outcomes in metastatic and nonmetastatic BC. However, the development of ET resistance promotes cancer survival and progression and hinders the use of endocrine agents. Several mechanisms implicated in endocrine resistance have now been extensively studied. Based on the current clinical and pre-clinical data, the present article briefly reviews the well-established pathways of ET resistance and continues by focusing on the three most recently uncovered pathways, which may mediate resistance to ET, namely receptor activator of nuclear factor kappa B ligand (RANKL)/receptor activator of nuclear factor kappa B (RANK), nuclear factor kappa B (NFκB), and Notch. It additionally overviews the evidence underlying the approval of combined therapies to overcome ET resistance in BC, while highlighting the relevance of future studies focusing on putative mediators of ET resistance to uncover new therapeutic options for the disease. ,Inês Soares de Pinho ... Luís Costa [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [86] => Array ( [ArticleId] => 332 [Create_Time] => 2022-06-22 [zipUrl] => https://www.explorationpub.com/uploads/zip/202206/20220622064038.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100287/100287.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100287/100287.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100287/100287_cover.png [JournalsId] => 4 [Title] => Liquid biopsy in biliary tract cancer from blood and bile samples: current knowledge and future perspectives [Abstract] => Biliary tract cancer (BTC) is an aggressive tumor characterized by a poor prognosis. In the latest years, targetable genetic alterations have been discovered in BTC patients, leading to the approval [AbstractComplete] =>Biliary tract cancer (BTC) is an aggressive tumor characterized by a poor prognosis. In the latest years, targetable genetic alterations have been discovered in BTC patients, leading to the approval of new targeted therapies. Liquid biopsy, which is a non-invasive method for detecting tumor biomarkers from fluid samples, is a useful tool for diagnosis and molecular characterization, but also for prognosis assessment and monitoring of treatment response. In this review, recent works on liquid biopsy in BTC patients were analyzed, focusing on some relevant aspects for clinical use and trying to depict the future role of this technique. Moreover, differences between plasma and bile samples were pointed out, in light of the peculiar biology of BTC and the possibility of using bile as an alternative source of cell-free DNA (cfDNA) for genomic analysis. In the era of precision oncology, the increasing adoption of liquid biopsy in BTC patients will certainly improve the management of this disease.
[Names] => Gianluca Arrichiello ... Emilio Francesco Giunta [Doi] => 10.37349/etat.2022.00087 [Published] => June 22, 2022 [Viewed] => 1508 [Downloaded] => 47 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00087 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 61 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:362–374 [Recommend] => 0 [Keywords] => Biliary tract cancer, liquid biopsy, plasma, bile, tumor biomarkers [DetailTitle] => The Implementation of Liquid Biopsy in Clinical Practice for Different Solid Tumor [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/61 [Id] => 100287 [ris] => https://www.explorationpub.com/uploads/Article/A100287/9e9149c1afc99b684e0863f87c686eb1.ris [bib] => https://www.explorationpub.com/uploads/Article/A100287/cb79ead0be8360c74a52768d60c0c286.bib [ens] => [Cited] => 5 [Cited_Time] => 2024-04-27 [CitethisArticle] => Arrichiello G, Nacca V, Paragliola F, Giunta EF. Liquid biopsy in biliary tract cancer from blood and bile samples: current knowledge and future perspectives. Explor Target Antitumor Ther. 2022;3:362–74. https://doi.org/10.37349/etat.2022.00087 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-06-22 01:22:55 [Bib_Time] => 2022-06-22 01:22:55 [KeysWordContens] => Liquid biopsy in biliary tract cancer from blood and bile samples: current knowledge and future perspectives, Biliary tract cancer, liquid biopsy, plasma, bile, tumor biomarkers, Biliary tract cancer (BTC) is an aggressive tumor characterized by a poor prognosis. In the latest years, targetable genetic alterations have been discovered in BTC patients, leading to the approval of new targeted therapies. Liquid biopsy, which is a non-invasive method for detecting tumor biomarkers from fluid samples, is a useful tool for diagnosis and molecular characterization, but also for prognosis assessment and monitoring of treatment response. In this review, recent works on liquid biopsy in BTC patients were analyzed, focusing on some relevant aspects for clinical use and trying to depict the future role of this technique. Moreover, differences between plasma and bile samples were pointed out, in light of the peculiar biology of BTC and the possibility of using bile as an alternative source of cell-free DNA (cfDNA) for genomic analysis. In the era of precision oncology, the increasing adoption of liquid biopsy in BTC patients will certainly improve the management of this disease. ,Gianluca Arrichiello ... Emilio Francesco Giunta [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [87] => Array ( [ArticleId] => 336 [Create_Time] => 2022-06-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202206/20220630002618.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100288/100288.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100288/100288.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100288/100288_cover.png [JournalsId] => 4 [Title] => Allosteric cross-talk between the hydrophobic cleft and the BH4 domain of Bcl-2 in control of inositol 1,4,5-trisphosphate receptor activity [Abstract] => Aim: Inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitous calcium (Ca2+) channel involved in the regulation of cellular fate and motility. Its modulation by anti-apoptotic prote [AbstractComplete] =>Inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitous calcium (Ca2+) channel involved in the regulation of cellular fate and motility. Its modulation by anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) plays an important role in cancer progression. Disrupting this interaction could overcome apoptosis avoidance, one of the hallmarks of cancer, and is, thus, of great interest. Earlier reports have shown the involvement of both the Bcl-2 homology 4 (BH4) and the transmembrane domains (TMDs) of Bcl-2 in regulating IP3R activity, while the Bcl-2 hydrophobic cleft was associated primarily with its anti-apoptotic and IP3R-independent action at the mitochondria (Oncotarget. 2016;7:55704–20. doi: 10.18632/oncotarget.11005). The aim of this study was to investigate how targeting the BH3 hydrophobic cleft of Bcl-2 affects IP3R:Bcl-2 interaction.
Organelle membrane-derived (OMD) patch-clamp and circular dichroism (CD) thermal melting experiments were used to elucidate the effects of the ABT-199 (venetoclax) on the IP3R:Bcl-2 interaction. Molecular dynamics (MD) simulations of free and ABT-199 bound Bcl-2 were used to propose a molecular model of such interaction.
It was shown that occlusion of Bcl-2’s hydrophobic cleft by the drug ABT-199 finely modulates IP3R gating in the low open probability (Po) regime, characteristic of the basal IP3R activity in non-excited cells. Complementary MD simulations allowed to propose a model of this modulation, involving an allosteric interaction with the BH4 domain on the opposite side of Bcl-2.
Bcl-2 is an important regulator of IP3R activity and, thus of Ca2+ release from internal stores and associated processes, including cellular proliferation and death. The presence of multiple regulatory domains in both proteins suggests a complex interaction. Thus, it was found that the occlusion of the hydrophobic cleft of Bcl-2 by ABT-199 disrupts IP3R activity, leading to Bcl-2 rebinding with smaller affinity and lesser inhibitory effect. MDs simulations of free and ABT-199 bound Bcl-2 propose a molecular model of such disruption, involving an allosteric interaction with the BH4 domain on the opposite side of Bcl-2.
Neuroendocrine tumor (NET) is a rare tumor that has been observed in different sites such as lungs and throughout the gastrointestinal tract. Clinical features are usually non-specific and vary considerably depending upon the location of the tumor. Symptoms are similar to those of common conditions such as peptic ulcer disease, gastritis, irritable bowel syndrome, asthma, etc. Thus, an initial diagnosis of a NET usually occurs at an advanced stage. This report describes a case of pancreatic NET (PNET, grade 2) with liver metastasis in a 37-year-old male which was found to be inoperable due to extensive direct involvement of the proximal jejunal branches and superior mesenteric vein. Peptide receptor radionuclide therapy (PRRT) with lutetium-177 dotatate (177Lu-DOTATATE) was administered due to the inoperability of primary PNET. Complete resolution of symptoms occurred with three cycles of PRRT.
[Names] => Amit Kumar ... Rohit Kumar [Doi] => 10.37349/etat.2022.00089 [Published] => June 29, 2022 [Viewed] => 1073 [Downloaded] => 69 [Subject] => Case Report [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00089 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:392–397 [Recommend] => 0 [Keywords] => Neoplasm metastasis, neuroendocrine tumors, pancreas, peptide receptor radionuclide therapy [DetailTitle] => [DetailUrl] => [Id] => 100289 [ris] => https://www.explorationpub.com/uploads/Article/A100289/bcbfc1549652f924bfee11e76bbc2305.ris [bib] => https://www.explorationpub.com/uploads/Article/A100289/ae2c0685fb586a7342a3ac6272b071c3.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Kumar A, Tanwar S, Gupta S, Chetiwal R, Kumar R. Advanced metastatic pancreatic neuroendocrine tumor treated successfully with peptide receptor radionuclide therapy: a case report. Explor Target Antitumor Ther. 2022;3:392–7. https://doi.org/10.37349/etat.2022.00089 [Jindex] => 0 [CName] => RajeshChetiwal, [CEmail] => dr.rchetiwal@gmail.com, [Ris_Time] => 2022-06-28 01:03:57 [Bib_Time] => 2022-06-28 01:03:57 [KeysWordContens] => Advanced metastatic pancreatic neuroendocrine tumor treated successfully with peptide receptor radionuclide therapy: a case report, Neoplasm metastasis, neuroendocrine tumors, pancreas, peptide receptor radionuclide therapy, Neuroendocrine tumor (NET) is a rare tumor that has been observed in different sites such as lungs and throughout the gastrointestinal tract. Clinical features are usually non-specific and vary considerably depending upon the location of the tumor. Symptoms are similar to those of common conditions such as peptic ulcer disease, gastritis, irritable bowel syndrome, asthma, etc. Thus, an initial diagnosis of a NET usually occurs at an advanced stage. This report describes a case of pancreatic NET (PNET, grade 2) with liver metastasis in a 37-year-old male which was found to be inoperable due to extensive direct involvement of the proximal jejunal branches and superior mesenteric vein. Peptide receptor radionuclide therapy (PRRT) with lutetium-177 dotatate (177Lu-DOTATATE) was administered due to the inoperability of primary PNET. Complete resolution of symptoms occurred with three cycles of PRRT. ,Amit Kumar ... Rohit Kumar [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [89] => Array ( [ArticleId] => 339 [Create_Time] => 2022-07-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202206/20220630035717.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100290/100290.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100290/100290.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100290/100290_cover.png [JournalsId] => 4 [Title] => Combination of thermal ablation by focused ultrasound, pFAR4-IL-12 transfection and lipidic adjuvant provide a distal immune response [Abstract] => Aim: Gene-based immunotherapy against cancer is limited by low gene transfer efficiency. In the literature, interleukin-12 (IL-12) encoding plasmid associated with sonoporation has been shown to en [AbstractComplete] =>Gene-based immunotherapy against cancer is limited by low gene transfer efficiency. In the literature, interleukin-12 (IL-12) encoding plasmid associated with sonoporation has been shown to enhance antitumoral activity. Moreover, non-viral carriers and high-frequency ultrasound have both been shown to promote immune response activation. Here, IL-12 encoding plasmid, non-viral carrier stimulating the immune response and focused ultrasound were combined in order to improve the antitumoral efficiency.
In order to enhance a gene-based antitumoral immune response, home-made lipids Toll-like receptor 2 (TLR2) agonists and plasmid free of antibiotic resistance version 4 (pFAR4), a mini-plasmid, encoding the IL-12 cytokine were combined with high-intensity focused ultrasound (HIFU). The lipid composition and the combination conditions were selected following in vitro and in vivo preliminary studies. The expression of IL-12 from our plasmid construct was measured in vitro and in vivo. The combination strategy was evaluated in mice bearing colon carcinoma cells (CT26) tumors following their weight, tumor volume, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) levels in the serum and produced by splenocytes exposed to CT26 tumor cells.
Lipid-mediated cell transfection and intratumoral injection into CT26 tumor mice using pFAR4-IL-12 led to the secretion of the IL-12 cytokine into cell supernatant and mice sera, respectively. Conditions of thermal deposition using HIFU were optimized. The plasmid encoding pFAR4-IL-12 or TLR2 agonist alone had no impact on tumor growth compared with control mice, whereas the complete treatment consisting of pFAR4-IL-12, TLR2 lipid agonist, and HIFU limited tumor growth. Moreover, only the complete treatment increased significantly mice survival and provided an abscopal effect on a metastatic CT26 model.
The HIFU condition was highly efficient to stop tumor growth. The combined therapy was the most efficient in terms of IL-12 and IFN-γ production and mice survival. The study showed the feasibility and the limits of this combined therapy which has the potential to be improved.
To evaluate the local impact of the coronavirus disease 2019 (COVID-19) pandemic on breast cancer (BC) care, with particular attention to the economical and psychological consequences of the possible delay of new diagnoses and treatments.
Three years’ activity (from 2019 to 2021) has been compared. The number of BCs diagnosed from the total amount of mammographic and ultrasound (US) examinations performed in women aged more than 40 years old has been considered. A Pearson’s chi-squared test was performed to verify differences between results. Statistical significance was set at P ≤ 0.01.
A statistically significant difference was found in the number of BC diagnosed between screening and ambulatory care patients in both the 2019–2020 (χ2 = 24.93, P < 0.01) and 2019–2021 (χ2 = 29.93, P < 0.01) comparisons. No statistically significant difference was found in the data recorded between 2020 and 2021 (χ2 = 2.35, P > 0.01). By evaluating the specific age groups for each year, a statistically significant difference (P < 0.01) was found in the number of BC diagnosed in screening patients aged 50–69 years old in both 2019–2020 and 2019–2021 comparisons. The percentages of early BC diagnosed in 2019, 2020, and 2021 were 80.9%, 91.7%, and 89.8%, respectively. The adherence rates to screening in 2019, 2020, and 2021 were 67.5%, 45.2%, and 56.9%, respectively.
Results showed a reduction of new diagnoses in the screening range during the pandemic in comparison with the previous period. The high percentage of early BC would seem to have prevented worsening outcomes. Nevertheless, women who have not undergone screening could present a more advanced stage disease in the following years. Consequently, the evaluation of possible solutions to guarantee an essential level of care with the purpose to avoid worsening patients’ outcomes and the increase in healthcare costs is mandatory.
Compared to humans, plants can synthesize an extremely diverse array of chemical compounds, including phenolic acids, flavonoids, stilbenes, lignans, terpenoids, alkaloids, and many other types of secondary metabolites that have been demonstrated to exert important bioactivities and impacts on the human health. As a result of extensive and sustained efforts, some phytochemicals like vincristine, vinblastine, and paclitaxel have already been approved as anticancer drugs today, while several others are under clinical trials. However, despite this remarkable success, studies on anticancer action of plant-derived products have been and paradoxically are still in some places, mixed up with alternative approaches and thereby considered non-credible, especially in regions where the role of traditional medicine has not been historically so prevalent as in several Asian countries. As a result, only about 10% of higher plants have been explored regarding the potential therapeutic effects of their constituents. Moreover, as one function of secondary metabolites includes the protection of plants against diverse environmental stresses, the content and composition of these phytochemicals might importantly vary between different regional habitats. Therefore, the stereotyped attitudes to plant products as something related to alternative medicine must be changed to identify new lead molecules for novel anticancer drugs. It is possible that plants still harbor an important spectrum of pharmaceutically interesting, but still unidentified, chemical compounds.
[Names] => Katrin Sak [Doi] => 10.37349/etat.2022.00092 [Published] => August 15, 2022 [Viewed] => 1090 [Downloaded] => 46 [Subject] => Perspective [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00092 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 73 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:423–427 [Recommend] => 0 [Keywords] => Natural anticancer products, phytochemicals, chemotherapeutic drugs [DetailTitle] => Plant Extracts as an Infinite Resource for New Anticancer Agents [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/73 [Id] => 100292 [ris] => https://www.explorationpub.com/uploads/Article/A100292/cb1ebc83d0209b4aec5e40644046e860.ris [bib] => https://www.explorationpub.com/uploads/Article/A100292/6be4da4e96e787f24f4a31d34600c7b5.bib [ens] => [Cited] => 5 [Cited_Time] => 2024-04-26 [CitethisArticle] => Sak K. Anticancer action of plant products: changing stereotyped attitudes. Explor Target Antitumor Ther. 2022;3:423–7. https://doi.org/10.37349/etat.2022.00092 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-08-15 09:45:32 [Bib_Time] => 2022-08-30 05:56:43 [KeysWordContens] => Anticancer action of plant products: changing stereotyped attitudes, Natural anticancer products, phytochemicals, chemotherapeutic drugs, Compared to humans, plants can synthesize an extremely diverse array of chemical compounds, including phenolic acids, flavonoids, stilbenes, lignans, terpenoids, alkaloids, and many other types of secondary metabolites that have been demonstrated to exert important bioactivities and impacts on the human health. As a result of extensive and sustained efforts, some phytochemicals like vincristine, vinblastine, and paclitaxel have already been approved as anticancer drugs today, while several others are under clinical trials. However, despite this remarkable success, studies on anticancer action of plant-derived products have been and paradoxically are still in some places, mixed up with alternative approaches and thereby considered non-credible, especially in regions where the role of traditional medicine has not been historically so prevalent as in several Asian countries. As a result, only about 10% of higher plants have been explored regarding the potential therapeutic effects of their constituents. Moreover, as one function of secondary metabolites includes the protection of plants against diverse environmental stresses, the content and composition of these phytochemicals might importantly vary between different regional habitats. Therefore, the stereotyped attitudes to plant products as something related to alternative medicine must be changed to identify new lead molecules for novel anticancer drugs. It is possible that plants still harbor an important spectrum of pharmaceutically interesting, but still unidentified, chemical compounds. ,Katrin Sak [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [92] => Array ( [ArticleId] => 373 [Create_Time] => 2022-08-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202208/20220831022634.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100293/100293.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100293/100293.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100293/100293_cover.png [JournalsId] => 4 [Title] => Applications and challenges of biomaterial mediated mRNA delivery [Abstract] => With the rapid development of gene therapy technology and the outbreak of coronavirus disease 2019 (COVID-19), messenger RNA (mRNA) therapeutics have attracted more and more attention, and the COVID [AbstractComplete] =>With the rapid development of gene therapy technology and the outbreak of coronavirus disease 2019 (COVID-19), messenger RNA (mRNA) therapeutics have attracted more and more attention, and the COVID-19 mRNA vaccine has been approved by the Food and Drug Administration (FDA) for emergency authorization. To improve the delivery efficiency of mRNA in vitro and in vivo, researchers have developed a variety of mRNA carriers and explored different administration routes. This review will systematically introduce the types of mRNA vectors, routes of administration, storage methods, safety of mRNA therapeutics, and the type of diseases that mRNA drugs are applied for. Finally, some suggestions are supplied on the development direction of mRNA therapeutic agents in the future.
[Names] => Huapan Fang, Qian Chen [Doi] => 10.37349/etat.2022.00093 [Published] => August 31, 2022 [Viewed] => 1742 [Downloaded] => 42 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00093 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 51 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:428–444 [Recommend] => 0 [Keywords] => Messenger RNA therapeutics, delivery efficiency, messenger RNA vectors, routes of administration, storage methods, safety [DetailTitle] => Gene Delivery Approach to Fight Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/51 [Id] => 100293 [ris] => https://www.explorationpub.com/uploads/Article/A100293/ab86fe435fdae13b79458bc223f5ed95.ris [bib] => https://www.explorationpub.com/uploads/Article/A100293/9abfe410af71a0b6229c824ddb7219ff.bib [ens] => [Cited] => 5 [Cited_Time] => 2024-04-27 [CitethisArticle] => Fang H, Chen Q. Applications and challenges of biomaterial mediated mRNA delivery. Explor Target Antitumor Ther. 2022;3:428-44. https://doi.org/10.37349/etat.2022.00093 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-08-30 05:55:55 [Bib_Time] => 2022-08-30 05:55:55 [KeysWordContens] => Applications and challenges of biomaterial mediated mRNA delivery, Messenger RNA therapeutics, delivery efficiency, messenger RNA vectors, routes of administration, storage methods, safety, With the rapid development of gene therapy technology and the outbreak of coronavirus disease 2019 (COVID-19), messenger RNA (mRNA) therapeutics have attracted more and more attention, and the COVID-19 mRNA vaccine has been approved by the Food and Drug Administration (FDA) for emergency authorization. To improve the delivery efficiency of mRNA in vitro and in vivo, researchers have developed a variety of mRNA carriers and explored different administration routes. This review will systematically introduce the types of mRNA vectors, routes of administration, storage methods, safety of mRNA therapeutics, and the type of diseases that mRNA drugs are applied for. Finally, some suggestions are supplied on the development direction of mRNA therapeutic agents in the future. ,Huapan Fang, Qian Chen [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [93] => Array ( [ArticleId] => 375 [Create_Time] => 2022-08-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202208/20220831060336.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100294/100294.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100294/100294.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100294/100294_cover.png [JournalsId] => 4 [Title] => Roles of calcium signaling in cancer metastasis to bone [Abstract] => Bone metastasis is a frequent complication for cancers and an important reason for the mortality in cancer patients. After surviving in bone, cancer cells can cause severe pain, life-threatening hyp [AbstractComplete] =>Bone metastasis is a frequent complication for cancers and an important reason for the mortality in cancer patients. After surviving in bone, cancer cells can cause severe pain, life-threatening hypercalcemia, pathologic fractures, spinal cord compression, and even death. However, the underlying mechanisms of bone metastasis were not clear. The role of calcium (Ca2+) in cancer cell proliferation, migration, and invasion has been well established. Interestingly, emerging evidence indicates that Ca2+ signaling played a key role in bone metastasis, for it not only promotes cancer progression but also mediates osteoclasts and osteoblasts differentiation. Therefore, Ca2+ signaling has emerged as a novel therapeutical target for cancer bone metastasis treatments. Here, the role of Ca2+ channels and Ca2+-binding proteins including calmodulin and Ca2+-sensing receptor in bone metastasis, and the perspective of anti-cancer bone metastasis therapeutics via targeting the Ca2+ signaling pathway are summarized.
[Names] => Tianying Xie ... Jianru Xiao [Doi] => 10.37349/etat.2022.00094 [Published] => August 31, 2022 [Viewed] => 1523 [Downloaded] => 44 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/etat.2022.00094 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 35 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:445–462 [Recommend] => 0 [Keywords] => Bone metastasis, calcium, calcium channels, calcium-sensing receptor, calmodulin [DetailTitle] => Calcium Signaling Apparatus in Cancers [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/35 [Id] => 100294 [ris] => https://www.explorationpub.com/uploads/Article/A100294/1ff8b9f36b18c69bcb0dd2d1b5926c7f.ris [bib] => https://www.explorationpub.com/uploads/Article/A100294/b7049c38a444e30e33c522287b701143.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Xie T, Chen S, Hao J, Wu P, Gu X, Wei H, et al. Roles of calcium signaling in cancer metastasis to bone. Explor Target Antitumor Ther. 2022;3:445–62. https://doi.org/10.37349/etat.2022.00094 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-08-31 01:14:23 [Bib_Time] => 2022-08-31 01:14:23 [KeysWordContens] => Roles of calcium signaling in cancer metastasis to bone, Bone metastasis, calcium, calcium channels, calcium-sensing receptor, calmodulin, Bone metastasis is a frequent complication for cancers and an important reason for the mortality in cancer patients. After surviving in bone, cancer cells can cause severe pain, life-threatening hypercalcemia, pathologic fractures, spinal cord compression, and even death. However, the underlying mechanisms of bone metastasis were not clear. The role of calcium (Ca2+) in cancer cell proliferation, migration, and invasion has been well established. Interestingly, emerging evidence indicates that Ca2+ signaling played a key role in bone metastasis, for it not only promotes cancer progression but also mediates osteoclasts and osteoblasts differentiation. Therefore, Ca2+ signaling has emerged as a novel therapeutical target for cancer bone metastasis treatments. Here, the role of Ca2+ channels and Ca2+-binding proteins including calmodulin and Ca2+-sensing receptor in bone metastasis, and the perspective of anti-cancer bone metastasis therapeutics via targeting the Ca2+ signaling pathway are summarized. ,Tianying Xie ... Jianru Xiao [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [94] => Array ( [ArticleId] => 376 [Create_Time] => 2022-08-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202208/20220831093205.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100295/100295.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100295/100295.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100295/100295_cover.png [JournalsId] => 4 [Title] => A personalized molecular approach in multiple myeloma: the possible use of RAF/RAS/MEK/ERK and BCL-2 inhibitors [Abstract] => Multiple myeloma (MM) is a blood cancer that derives from plasma cells (PCs), which will accumulate in the bone marrow (BM). Over time, several drugs have been developed to treat this disease that i [AbstractComplete] =>Multiple myeloma (MM) is a blood cancer that derives from plasma cells (PCs), which will accumulate in the bone marrow (BM). Over time, several drugs have been developed to treat this disease that is still uncurable. The therapies used to treat the disease target immune activity, inhibit proteasome activity, and involve the use of monoclonal antibodies. However, MM is a highly heterogeneous disease, in fact, there are several mutations in signaling pathways that are particularly important for MM cell biology and that are possible therapeutic targets. Indeed, some studies suggest that MM is driven by mutations within the rat sarcoma virus (RAS) signaling cascade, which regulates cell survival and proliferation. The RAS/proto-oncogene, serine/threonine kinase (RAF)/mitogen-activated extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway is deregulated in several cancers, for which drugs have been developed to inhibit these pathways. In addition to the signaling pathways, the disease implements mechanisms to ensure the survival and consequently a high replicative capacity. This strategy consists in the deregulation of apoptosis. In particular, some cases of MM show overexpression of anti-apoptotic proteins belonging to the B cell lymphoma 2 (BCL-2) family that represent a possible druggable target. Venetoclax is an anti-BCL-2 molecule used in hematological malignancies that may be used in selected MM patients based on their molecular profile. We focused on the possible effects in MM of off-label drugs that are currently used for other cancers with the same molecular characteristics. Their use, combined with the current treatments, could be a good strategy against MM.
[Names] => Vincenzo Raimondi ... Nicola Giuliani [Doi] => 10.37349/etat.2022.00095 [Published] => August 31, 2022 [Viewed] => 1535 [Downloaded] => 36 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00075 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 32 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:463–479 [Recommend] => 0 [Keywords] => Multiple myeloma, mitogen-activated protein kinases pathway, B cell lymphoma 2, venetoclax [DetailTitle] => Off-label drugs and -omics data in cancer treatment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/32 [Id] => 100295 [ris] => https://www.explorationpub.com/uploads/Article/A100295/09a42eda8ae5cff082f0e9986cbb5475.ris [bib] => https://www.explorationpub.com/uploads/Article/A100295/715038ce549d6f439727b61e84aaa294.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-26 [CitethisArticle] => Raimondi V, Iannozzi NT, Burroughs-Garcìa J, Toscani D, Storti P, Giuliani N. A personalized molecular approach in multiple myeloma: the possible use of RAF/RAS/MEK/ERK and BCL-2 inhibitors. Explor Target Antitumor Ther. 2022;3:463–79. https://doi.org/10.37349/etat.2022.00095 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-08-30 05:57:35 [Bib_Time] => 2022-08-30 05:57:35 [KeysWordContens] => A personalized molecular approach in multiple myeloma: the possible use of RAF/RAS/MEK/ERK and BCL-2 inhibitors, Multiple myeloma, mitogen-activated protein kinases pathway, B cell lymphoma 2, venetoclax, Multiple myeloma (MM) is a blood cancer that derives from plasma cells (PCs), which will accumulate in the bone marrow (BM). Over time, several drugs have been developed to treat this disease that is still uncurable. The therapies used to treat the disease target immune activity, inhibit proteasome activity, and involve the use of monoclonal antibodies. However, MM is a highly heterogeneous disease, in fact, there are several mutations in signaling pathways that are particularly important for MM cell biology and that are possible therapeutic targets. Indeed, some studies suggest that MM is driven by mutations within the rat sarcoma virus (RAS) signaling cascade, which regulates cell survival and proliferation. The RAS/proto-oncogene, serine/threonine kinase (RAF)/mitogen-activated extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway is deregulated in several cancers, for which drugs have been developed to inhibit these pathways. In addition to the signaling pathways, the disease implements mechanisms to ensure the survival and consequently a high replicative capacity. This strategy consists in the deregulation of apoptosis. In particular, some cases of MM show overexpression of anti-apoptotic proteins belonging to the B cell lymphoma 2 (BCL-2) family that represent a possible druggable target. Venetoclax is an anti-BCL-2 molecule used in hematological malignancies that may be used in selected MM patients based on their molecular profile. We focused on the possible effects in MM of off-label drugs that are currently used for other cancers with the same molecular characteristics. Their use, combined with the current treatments, could be a good strategy against MM. ,Vincenzo Raimondi ... Nicola Giuliani [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [95] => Array ( [ArticleId] => 378 [Create_Time] => 2022-08-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202208/20220831013032.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100296/100296.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100296/100296.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100296/100296_cover.png [JournalsId] => 4 [Title] => Endocrine therapy resistance: what we know and future directions [Abstract] => Endocrine resistance is a major hurdle in the treatment of estrogen receptor (ER)-positive breast cancer. When abnormally regulated, molecular signals responsible for cellular proliferation, as well [AbstractComplete] =>Endocrine resistance is a major hurdle in the treatment of estrogen receptor (ER)-positive breast cancer. When abnormally regulated, molecular signals responsible for cellular proliferation, as well as ER itself, allow for cellular evasion of ER-dependent treatments. Therefore, pharmacological treatments that target these evasion mechanisms are beneficial for the treatment of endocrine-resistant breast cancers. This review summarizes currently understood molecular signals that contribute to endocrine resistance and their crosstalk that stem from mitogen-activated protein kinase (MAPK), phosphoinositol-3 kinase/protein kinase B (PI3K/AKT), mechanistic target of rapamycin (mTOR), cyclin-dependent kinases 4 and 6 (CDK4/6) and aberrant ER function. Recent clinical trials that target these molecular signals as a treatment strategy for endocrine-resistant breast cancer are also highlighted.
[Names] => David Musheyev, Anya Alayev [Doi] => 10.37349/etat.2022.00096 [Published] => August 31, 2022 [Viewed] => 1464 [Downloaded] => 21 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00096 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 48 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:480–496 [Recommend] => 0 [Keywords] => Endocrine resistance, estrogen receptor-positive, signaling crosstalk [DetailTitle] => Endocrine Resistant Breast Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/48 [Id] => 100296 [ris] => https://www.explorationpub.com/uploads/Article/A100296/dd4a13d7205cba57c5e2aff63b3acc17.ris [bib] => https://www.explorationpub.com/uploads/Article/A100296/8e767ff6f6b3287d0ce21704f8ea475c.bib [ens] => [Cited] => 5 [Cited_Time] => 2024-04-27 [CitethisArticle] => Musheyev D, Alayev A. Endocrine therapy resistance: what we know and future directions. Explor Target Antitumor Ther. 2022;3:480–96. https://doi.org/10.37349/etat.2022.00096 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-08-30 06:06:37 [Bib_Time] => 2022-08-30 06:06:57 [KeysWordContens] => Endocrine therapy resistance: what we know and future directions, Endocrine resistance, estrogen receptor-positive, signaling crosstalk, Endocrine resistance is a major hurdle in the treatment of estrogen receptor (ER)-positive breast cancer. When abnormally regulated, molecular signals responsible for cellular proliferation, as well as ER itself, allow for cellular evasion of ER-dependent treatments. Therefore, pharmacological treatments that target these evasion mechanisms are beneficial for the treatment of endocrine-resistant breast cancers. This review summarizes currently understood molecular signals that contribute to endocrine resistance and their crosstalk that stem from mitogen-activated protein kinase (MAPK), phosphoinositol-3 kinase/protein kinase B (PI3K/AKT), mechanistic target of rapamycin (mTOR), cyclin-dependent kinases 4 and 6 (CDK4/6) and aberrant ER function. Recent clinical trials that target these molecular signals as a treatment strategy for endocrine-resistant breast cancer are also highlighted. ,David Musheyev, Anya Alayev [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [96] => Array ( [ArticleId] => 379 [Create_Time] => 2022-08-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202209/20220901032655.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100297/100297.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100297/100297.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100297/100297_cover.png [JournalsId] => 4 [Title] => Myeloid-derived suppressor cells in colorectal cancer: prognostic biomarkers and therapeutic targets [Abstract] => Myeloid-derived suppressor cells (MDSCs) are a group of immature myeloid cells, which are expanded in most cancer patients. MDSCs suppress host immune responses, leading to cancer growth and progres [AbstractComplete] =>Myeloid-derived suppressor cells (MDSCs) are a group of immature myeloid cells, which are expanded in most cancer patients. MDSCs suppress host immune responses, leading to cancer growth and progression. Several studies demonstrated that there was a relationship between levels of MDSCs and tumorigenesis in colorectal cancer (CRC) patients. MDSCs are now being investigated for their role as possible therapeutic targets in cancer treatment. This review summarizes available studies that investigated MDSC expansion in CRC patients, as well as their role in CRC tumorigenesis, prognosis, and targeting. Based on the available studies, there is a possible relationship between high levels of MDSCs and CRC progression. Additionally, targeting MDSCs in CRC patients selectively represents a significant challenge for the development of targeted treatments. Targeting of MDSCs could be exploited in different ways including MDSC depletion, inhibition of MDSC function and recruitment, and enhancing MDSC differentiation. Overall, MDSCs could be exploited as prognostic biomarkers and potential therapeutic targets in CRC.
[Names] => Mohammad A. Al-Mterin, Eyad Elkord [Doi] => 10.37349/etat.2022.00097 [Published] => August 31, 2022 [Viewed] => 1604 [Downloaded] => 51 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00097 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 70 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:497–510 [Recommend] => 0 [Keywords] => Myeloid-derived suppressor cells, colorectal cancer, prognostic biomarkers, targeting [DetailTitle] => Cancer Immunotherapy and Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/70 [Id] => 100297 [ris] => https://www.explorationpub.com/uploads/Article/A100297/a8809d7d7902ae977ac0347277dbc91c.ris [bib] => https://www.explorationpub.com/uploads/Article/A100297/6b0661de720dec557b6450da589a8fd0.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-26 [CitethisArticle] => Al-Mterin MA, Elkord E. Myeloid-derived suppressor cells in colorectal cancer: prognostic biomarkers and therapeutic targets. Explor Target Antitumor Ther. 2022;3:497–510. https://doi.org/10.37349/etat.2022.00097 [Jindex] => 0 [CName] => EyadElkord, [CEmail] => e.elkord@unizwa.edu.om, [Ris_Time] => 2022-08-31 01:23:48 [Bib_Time] => 2022-08-31 01:23:48 [KeysWordContens] => Myeloid-derived suppressor cells in colorectal cancer: prognostic biomarkers and therapeutic targets, Myeloid-derived suppressor cells, colorectal cancer, prognostic biomarkers, targeting, Myeloid-derived suppressor cells (MDSCs) are a group of immature myeloid cells, which are expanded in most cancer patients. MDSCs suppress host immune responses, leading to cancer growth and progression. Several studies demonstrated that there was a relationship between levels of MDSCs and tumorigenesis in colorectal cancer (CRC) patients. MDSCs are now being investigated for their role as possible therapeutic targets in cancer treatment. This review summarizes available studies that investigated MDSC expansion in CRC patients, as well as their role in CRC tumorigenesis, prognosis, and targeting. Based on the available studies, there is a possible relationship between high levels of MDSCs and CRC progression. Additionally, targeting MDSCs in CRC patients selectively represents a significant challenge for the development of targeted treatments. Targeting of MDSCs could be exploited in different ways including MDSC depletion, inhibition of MDSC function and recruitment, and enhancing MDSC differentiation. Overall, MDSCs could be exploited as prognostic biomarkers and potential therapeutic targets in CRC. ,Mohammad A. Al-Mterin, Eyad Elkord [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [97] => Array ( [ArticleId] => 380 [Create_Time] => 2022-09-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202209/20220923030740.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100298/100298.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100298/100298.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100298/100298_cover.png [JournalsId] => 4 [Title] => miRNA therapeutics in precision oncology: a natural premium to nurture [Abstract] => The dynamic spectrum of microRNA (miRNA) has grown significantly over the years with its identification and exploration in cancer therapeutics and is currently identified as an important resource fo [AbstractComplete] =>The dynamic spectrum of microRNA (miRNA) has grown significantly over the years with its identification and exploration in cancer therapeutics and is currently identified as an important resource for innovative strategies due to its functional behavior for gene regulation and modulation of complex biological networks. The progression of cancer is the consequence of uncontrolled, nonsynchronous procedural faults in the biological system. Diversified and variable cellular response of cancerous cells has always raised challenges in effective cancer therapy. miRNAs, a class of non-coding RNAs (ncRNAs), are the natural genetic gift, responsible to preserve the homeostasis of cell to nurture. The unprecedented significance of endogenous miRNAs has exhibited promising therapeutic potential in cancer therapeutics. Currently, miRNA mimic miR-34, and an antimiR aimed against miR-122 has entered the clinical trials for cancer treatments. This review, highlights the recent breakthroughs, challenges, clinical trials, and advanced delivery vehicles in the administration of miRNA therapies for precision oncology.
[Names] => Chakresh Kumar Jain ... R Suresh Kumar [Doi] => 10.37349/etat.2022.00098 [Published] => August 31, 2022 [Viewed] => 1197 [Downloaded] => 46 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00098 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:511–532 [Recommend] => 0 [Keywords] => microRNAs, miRBase, miRTarBase, cancer, liposomes [DetailTitle] => [DetailUrl] => [Id] => 100298 [ris] => https://www.explorationpub.com/uploads/Article/A100298/2aada4e100e29d38950afb4a9327a461.ris [bib] => https://www.explorationpub.com/uploads/Article/A100298/db3fb90808db0137070c12a6677331ec.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-26 [CitethisArticle] => Jain CK, Srivastava P, Pandey AK, Singh N, Kumar RS. miRNA therapeutics in precision oncology: a natural premium to nurture. Explor Target Antitumor Ther. 2022;3:511–32. https://doi.org/10.37349/etat.2022.00098 [Jindex] => 0 [CName] => Chakresh KumarJain, [CEmail] => ckj522@yahoo.com, [Ris_Time] => 2022-08-30 01:14:19 [Bib_Time] => 2022-08-30 01:14:19 [KeysWordContens] => miRNA therapeutics in precision oncology: a natural premium to nurture, microRNAs, miRBase, miRTarBase, cancer, liposomes, The dynamic spectrum of microRNA (miRNA) has grown significantly over the years with its identification and exploration in cancer therapeutics and is currently identified as an important resource for innovative strategies due to its functional behavior for gene regulation and modulation of complex biological networks. The progression of cancer is the consequence of uncontrolled, nonsynchronous procedural faults in the biological system. Diversified and variable cellular response of cancerous cells has always raised challenges in effective cancer therapy. miRNAs, a class of non-coding RNAs (ncRNAs), are the natural genetic gift, responsible to preserve the homeostasis of cell to nurture. The unprecedented significance of endogenous miRNAs has exhibited promising therapeutic potential in cancer therapeutics. Currently, miRNA mimic miR-34, and an antimiR aimed against miR-122 has entered the clinical trials for cancer treatments. This review, highlights the recent breakthroughs, challenges, clinical trials, and advanced delivery vehicles in the administration of miRNA therapies for precision oncology. ,Chakresh Kumar Jain ... R Suresh Kumar [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [98] => Array ( [ArticleId] => 382 [Create_Time] => 2022-09-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202208/20220831040537.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100299/100299.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100299/100299.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100299/100299_cover.png [JournalsId] => 4 [Title] => Clinical applications of liquid biopsy in HPV-negative and HPV-positive head and neck squamous cell carcinoma: advances and challenges [Abstract] => Head and neck squamous cell carcinomas (HNSCCs) represent the most common epithelial tumors that arise from mucosa of the oral cavity, pharynx, and larynx. The development of HNSCCs is usually assoc [AbstractComplete] =>Head and neck squamous cell carcinomas (HNSCCs) represent the most common epithelial tumors that arise from mucosa of the oral cavity, pharynx, and larynx. The development of HNSCCs is usually associated with tobacco use, alcohol consumption, and human papillomavirus (HPV) infection. Most HNSCCs are diagnosed in advanced states, leading to a worse clinical outcome. Screening tests based on potential biomarkers associated with HNSCCs could improve this scenario. Liquid biopsy has emerged as a promising area of cancer investigation, offering a minimally invasive approach to track circulating biomarkers in body fluids that could potentially contribute to the diagnosis, predict prognosis, and monitor response to treatment. This review will discuss translational studies describing the clinical applications of liquid biopsy in HPV-negative and HPV-positive HNSCCs focused on circulating nucleic acids [cell-free DNA (cfDNA) and cell-free RNA (cfRNA)], circulating tumor cells (CTCs), and extracellular vesicles (EVs), which can be found in plasma, serum, and saliva.
[Names] => Mariana Chantre-Justino ... Lucas Delmonico [Doi] => 10.37349/etat.2022.00099 [Published] => August 31, 2022 [Viewed] => 1803 [Downloaded] => 64 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00099 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 61 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:533–552 [Recommend] => 0 [Keywords] => Head and neck squamous cell carcinomas, liquid biopsy, cell-free DNA/cell-free RNA, microRNA, circulating tumor cells, extracellular vesicles [DetailTitle] => The Implementation of Liquid Biopsy in Clinical Practice for Different Solid Tumor [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/61 [Id] => 100299 [ris] => https://www.explorationpub.com/uploads/Article/A100299/70e069c50b09181c0651ef2894596f1c.ris [bib] => https://www.explorationpub.com/uploads/Article/A100299/9ad4b44c0997083e4017c78dade6a219.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Chantre-Justino M, Alves G, Delmonico L. Clinical applications of liquid biopsy in HPV‐negative and HPV‐positive head and neck squamous cell carcinoma: advances and challenges. Explor Target Antitumor Ther. 2022;3:533–52. https://doi.org/10.37349/etat.2022.00099 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-08-30 01:16:02 [Bib_Time] => 2022-08-30 01:16:02 [KeysWordContens] => Clinical applications of liquid biopsy in HPV-negative and HPV-positive head and neck squamous cell carcinoma: advances and challenges, Head and neck squamous cell carcinomas, liquid biopsy, cell-free DNA/cell-free RNA, microRNA, circulating tumor cells, extracellular vesicles, Head and neck squamous cell carcinomas (HNSCCs) represent the most common epithelial tumors that arise from mucosa of the oral cavity, pharynx, and larynx. The development of HNSCCs is usually associated with tobacco use, alcohol consumption, and human papillomavirus (HPV) infection. Most HNSCCs are diagnosed in advanced states, leading to a worse clinical outcome. Screening tests based on potential biomarkers associated with HNSCCs could improve this scenario. Liquid biopsy has emerged as a promising area of cancer investigation, offering a minimally invasive approach to track circulating biomarkers in body fluids that could potentially contribute to the diagnosis, predict prognosis, and monitor response to treatment. This review will discuss translational studies describing the clinical applications of liquid biopsy in HPV-negative and HPV-positive HNSCCs focused on circulating nucleic acids [cell-free DNA (cfDNA) and cell-free RNA (cfRNA)], circulating tumor cells (CTCs), and extracellular vesicles (EVs), which can be found in plasma, serum, and saliva. ,Mariana Chantre-Justino ... Lucas Delmonico [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [99] => Array ( [ArticleId] => 392 [Create_Time] => 2022-09-30 [zipUrl] => https://www.explorationpub.com/uploads/zip/202209/20220930025735.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002100/1002100.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002100/1002100.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002100/1002100_cover.png [JournalsId] => 4 [Title] => N6-methyladenosine-related microRNAs risk model trumps the isocitrate dehydrogenase mutation status as a predictive biomarker for the prognosis and immunotherapy in lower grade gliomas [Abstract] => Aim: Lower grade gliomas [LGGs; World Health Organization (WHO) grades 2 and 3], owing to the heterogeneity of their clinical behavior, present a therapeutic challenge to [AbstractComplete] =>Lower grade gliomas [LGGs; World Health Organization (WHO) grades 2 and 3], owing to the heterogeneity of their clinical behavior, present a therapeutic challenge to neurosurgeons. The aim of this study was to explore the N6-methyladenosine (m6A) modification landscape in the LGGs and to develop an m6A-related microRNA (miRNA) risk model to provide new perspectives for the treatment and prognostic assessment of LGGs.
Messenger RNA (mRNA) and miRNA expression data of LGGs were extracted from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. An m6A-related miRNA risk model was constructed via least absolute shrinkage and selection operator (LASSO), univariate, and multivariate Cox regression analysis. Next, Kaplan-Meier analysis, principal-component analysis (PCA), functional enrichment analysis, immune infiltrate analysis, dynamic nomogram, and drug sensitivity prediction were used to evaluate this risk model.
Firstly, six m6A-related miRNAs with independent prognostic value were selected based on clinical information and used to construct a risk model. Subsequently, compared with low-risk group, LGGs in the high-risk group had a higher m6A writer and reader scores, but a lower eraser score. Moreover, LGGs in the high-risk group had a significantly worse clinical prognosis than those in the low-risk group. Simultaneously, this risk model outperformed other clinicopathological variables in the prognosis prediction of LGGs. Immune infiltrate analysis revealed that the proportion of M2 macrophages, regulatory T (Treg) cells, and the expression levels of exhausted immune response markers were significantly higher in the high-risk group than in the low-risk group. Finally, this study constructed an easy-to-use and free dynamic nomogram to help clinicians use this risk model to aid in diagnosis and prognosis assessment.
This study developed a m6A-related risk model and uncovered two different m6A modification landscapes in LGGs. Moreover, this risk model may provide guidance and help in clinical prognosis assessment and immunotherapy response prediction for LGGs.
Solute carrier family 7 member 11 (SLC7A11; also known as xCT), a key component of the cystine/glutamate antiporter, is essential for the maintenance of cellular redox status and the regulation of tumor-associated ferroptosis. Accumulating evidence has demonstrated that xCT overexpression, resulting from different oncogenic and tumor suppressor signaling, promotes tumor progression and multidrug resistance partially via suppressing ferroptosis. In addition, recent studies have highlighted the role of xCT in regulating the metabolic flexibility in cancer cells. In this review, the xCT activities in intracellular redox balance and in ferroptotic cell death have been summarized. Moreover, the role of xCT in promoting tumor development, drug resistance, and nutrient dependency in cancer cells has been explored. Finally, different therapeutic strategies, xCT-based, for anti-cancer treatments have been discussed.
[Names] => Daniela Criscuolo ... Angela Celetti [Doi] => 10.37349/etat.2022.00101 [Published] => October 25, 2022 [Viewed] => 1237 [Downloaded] => 35 [Subject] => Commentary [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00101 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:570–581 [Recommend] => 0 [Keywords] => Solute carrier family 7 member 11 (SLC7A11), reactive oxygen species (ROS) tolerance, ferroptosis-regulators, coiled-coil domain containing 6 (CCDC6), cancer therapy [DetailTitle] => [DetailUrl] => [Id] => 1002101 [ris] => https://www.explorationpub.com/uploads/Article/A1002101/3bfd661c3b43e727b67122562cf41a91.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002101/5b393e7881a248ae9ff0ee67d84de55f.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Criscuolo D, Morra F, Celetti A. A xCT role in tumour-associated ferroptosis shed light on novel therapeutic options. Explor Target Antitumor Ther. 2022;3:570–81. https://doi.org/10.37349/etat.2022.00101 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-10-25 02:05:34 [Bib_Time] => 2022-10-25 02:05:34 [KeysWordContens] => A xCT role in tumour-associated ferroptosis shed light on novel therapeutic options, Solute carrier family 7 member 11 (SLC7A11), reactive oxygen species (ROS) tolerance, ferroptosis-regulators, coiled-coil domain containing 6 (CCDC6), cancer therapy, Solute carrier family 7 member 11 (SLC7A11; also known as xCT), a key component of the cystine/glutamate antiporter, is essential for the maintenance of cellular redox status and the regulation of tumor-associated ferroptosis. Accumulating evidence has demonstrated that xCT overexpression, resulting from different oncogenic and tumor suppressor signaling, promotes tumor progression and multidrug resistance partially via suppressing ferroptosis. In addition, recent studies have highlighted the role of xCT in regulating the metabolic flexibility in cancer cells. In this review, the xCT activities in intracellular redox balance and in ferroptotic cell death have been summarized. Moreover, the role of xCT in promoting tumor development, drug resistance, and nutrient dependency in cancer cells has been explored. Finally, different therapeutic strategies, xCT-based, for anti-cancer treatments have been discussed. ,Daniela Criscuolo ... Angela Celetti [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [101] => Array ( [ArticleId] => 414 [Create_Time] => 2022-10-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202210/20221028024039.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002102/1002102.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002102/1002102.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002102/1002102_cover.png [JournalsId] => 4 [Title] => Targeted RNA-sequencing analysis for fusion transcripts detection in tumor diagnostics: assessment of bioinformatic tools reliability in FFPE samples [Abstract] => Aim: Diagnostic laboratories are progressively introducing next-generation sequencing (NGS) technologies in the routine workflow to meet the increasing clinical need for comprehensive molecular c [AbstractComplete] =>Diagnostic laboratories are progressively introducing next-generation sequencing (NGS) technologies in the routine workflow to meet the increasing clinical need for comprehensive molecular characterization in cancer patients for diagnosis and precision medicine, including fusion-transcripts detection. Nevertheless, the low quality of messenger RNA (mRNA) extracted from formalin-fixed paraffin-embedded (FFPE) samples may affect the transition from traditional single-gene testing approaches [like fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), or polymerase chain reaction (PCR)] to NGS. The present study is aimed at assessing the overall accuracy of RNA fusion transcripts detection by NGS analysis in FFPE samples in real-world diagnostics.
Herein, NGS data from 190 soft tissue tumors (STTs) and carcinoma cases, discussed in the context of the institutional Molecular Tumor Board, are reported and analyzed by FusionPlex© Solid tumor kit through the manufacturer’s pipeline and by two well-known fast and accurate open-source tools [Arriba (ARR) and spliced transcripts alignment to reference (STAR)-fusion (SFU)].
The combination of FusionPlex© Solid tumor with ArcherDX® Analysis suite (ADx) analysis package has been proven to be sensitive and specific in STT samples, while partial loss of sensitivity has been found in carcinoma specimens.
Albeit ARR and SFU showed lower sensitivity, the use of additional fusion-detection tools can contribute to reinforcing or extending the output obtained by ADx, particularly in the case of low-quality input data. Overall, our results sustain the clinical use of NGS for the detection of fusion transcripts in FFPE material.
Cancer-associated fibroblasts (CAFs) are highly heterogeneous players that shape the tumor microenvironment and influence tumor progression, metastasis formation, and response to conventional therapies. During the past years, some CAFs subsets have also been involved in the modulation of immune cell functions, affecting the efficacy of both innate and adaptive anti-tumor immune responses. Consequently, the implication of these stromal cells in the response to immunotherapeutic strategies raised major concerns. In this review, current knowledge of CAFs origins and heterogeneity in the tumor stroma, as well as their effects on several immune cell populations that explain their immunosuppressive capabilities are summarized. The current development of therapeutic strategies for targeting this population and their implication in the field of cancer immunotherapy is also highlighted.
[Names] => Jerome Thiery [Doi] => 10.37349/etat.2022.00103 [Published] => October 27, 2022 [Viewed] => 1469 [Downloaded] => 26 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00103 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 70 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:598–629 [Recommend] => 0 [Keywords] => Tumor microenvironment, cancer-associated fibroblasts, immune suppression, cancer immunotherapy [DetailTitle] => Cancer Immunotherapy and Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/70 [Id] => 1002103 [ris] => https://www.explorationpub.com/uploads/Article/A1002103/44beb89dfa058f24232ec217c67ccadb.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002103/ea8baa53507f42f4a05455f0b281070e.bib [ens] => [Cited] => 4 [Cited_Time] => 2024-04-27 [CitethisArticle] => Thiery J. Modulation of the antitumor immune response by cancer-associated fibroblasts: mechanisms and targeting strategies to hamper their immunosuppressive functions. Explor Target Antitumor Ther. 2022;3:598–629. https://doi.org/10.37349/etat.2022.00103 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-10-25 03:29:41 [Bib_Time] => 2022-10-25 03:29:41 [KeysWordContens] => Modulation of the antitumor immune response by cancer-associated fibroblasts: mechanisms and targeting strategies to hamper their immunosuppressive functions, Tumor microenvironment, cancer-associated fibroblasts, immune suppression, cancer immunotherapy, Cancer-associated fibroblasts (CAFs) are highly heterogeneous players that shape the tumor microenvironment and influence tumor progression, metastasis formation, and response to conventional therapies. During the past years, some CAFs subsets have also been involved in the modulation of immune cell functions, affecting the efficacy of both innate and adaptive anti-tumor immune responses. Consequently, the implication of these stromal cells in the response to immunotherapeutic strategies raised major concerns. In this review, current knowledge of CAFs origins and heterogeneity in the tumor stroma, as well as their effects on several immune cell populations that explain their immunosuppressive capabilities are summarized. The current development of therapeutic strategies for targeting this population and their implication in the field of cancer immunotherapy is also highlighted. ,Jerome Thiery [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [103] => Array ( [ArticleId] => 417 [Create_Time] => 2022-10-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202305/20230524091814.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002104/1002104.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002104/1002104.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002104/1002104_cover.png [JournalsId] => 4 [Title] => Clinical utility of liquid biopsy-based companion diagnostics in the non-small-cell lung cancer treatment [Abstract] => Recently, technological advances in the detection and biological characterization of circulating tumor DNA (ctDNA) have enabled the implementation of liquid biopsy testing into clinical practice. Me [AbstractComplete] =>Recently, technological advances in the detection and biological characterization of circulating tumor DNA (ctDNA) have enabled the implementation of liquid biopsy testing into clinical practice. Methods for analysis of liquid biopsies have rapidly evolved over the past few years and have continued to advance, thus providing details about tumor biological characteristics such as tumor progression, metastasis, tumor heterogeneity, genomic mutation profile, clonal evolution, etc. In tandem with technological advances, the implementation of liquid biopsy in routine clinical settings has proceeded. In 2016, the Food and Drug Administration (FDA) approved the first ctDNA liquid biopsy test to detect epidermal growth factor receptor (EGFR) gene mutations in patients with non-small-cell lung cancer (NSCLC) as a companion diagnostic for molecular targeted drug of EGFR-tyrosine kinase inhibitor (TKI, EGFR-TKI). More recently, multigene panel assays of liquid biopsy have been approved as companion diagnostics and have been used in routine clinical settings. The estimation of blood tumor mutation burden (bTMB) to predict the efficacy of immune checkpoint inhibitor (ICI) treatment can be one of the promising approaches to liquid biopsy. The next stage of implementation of liquid biopsy for routine clinical settings is for monitoring of ctDNA after surgical treatment to predict prognosis and to detect disease relapse earlier than conventional imaging diagnosis. Its clinical utility is under assessment in several clinical trials. This review introduces recent advances in liquid biopsy methodology, the development of biomarkers, and its clinical utility in the treatment of NSCLC patients.
[Names] => Yoshiharu Sato [Doi] => 10.37349/etat.2022.00104 [Published] => October 31, 2022 [Viewed] => 1459 [Downloaded] => 24 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00104 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 61 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:630–642 [Recommend] => 0 [Keywords] => Liquid biopsy, companion diagnostics, genome informatics [DetailTitle] => The Implementation of Liquid Biopsy in Clinical Practice for Different Solid Tumor [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/61 [Id] => 1002104 [ris] => https://www.explorationpub.com/uploads/Article/A1002104/da9062a9e3d0575ae2fbcdbd6b7fb706.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002104/764b13b03d65dd7562f1fcef180d842b.bib [ens] => [Cited] => 7 [Cited_Time] => 2024-04-26 [CitethisArticle] => Sato Y. Clinical utility of liquid biopsy-based companion diagnostics in the non-small-cell lung cancer treatment. Explor Target Antitumor Ther. 2022;3:630–42. https://doi.org/10.37349/etat.2022.00104 [Jindex] => 0 [CName] => YoshiharuSato, [CEmail] => yo-sato@dna-chip.co.jp, [Ris_Time] => 2022-10-28 02:54:58 [Bib_Time] => 2022-10-28 02:54:58 [KeysWordContens] => Clinical utility of liquid biopsy-based companion diagnostics in the non-small-cell lung cancer treatment, Liquid biopsy, companion diagnostics, genome informatics, Recently, technological advances in the detection and biological characterization of circulating tumor DNA (ctDNA) have enabled the implementation of liquid biopsy testing into clinical practice. Methods for analysis of liquid biopsies have rapidly evolved over the past few years and have continued to advance, thus providing details about tumor biological characteristics such as tumor progression, metastasis, tumor heterogeneity, genomic mutation profile, clonal evolution, etc. In tandem with technological advances, the implementation of liquid biopsy in routine clinical settings has proceeded. In 2016, the Food and Drug Administration (FDA) approved the first ctDNA liquid biopsy test to detect epidermal growth factor receptor (EGFR) gene mutations in patients with non-small-cell lung cancer (NSCLC) as a companion diagnostic for molecular targeted drug of EGFR-tyrosine kinase inhibitor (TKI, EGFR-TKI). More recently, multigene panel assays of liquid biopsy have been approved as companion diagnostics and have been used in routine clinical settings. The estimation of blood tumor mutation burden (bTMB) to predict the efficacy of immune checkpoint inhibitor (ICI) treatment can be one of the promising approaches to liquid biopsy. The next stage of implementation of liquid biopsy for routine clinical settings is for monitoring of ctDNA after surgical treatment to predict prognosis and to detect disease relapse earlier than conventional imaging diagnosis. Its clinical utility is under assessment in several clinical trials. This review introduces recent advances in liquid biopsy methodology, the development of biomarkers, and its clinical utility in the treatment of NSCLC patients. ,Yoshiharu Sato [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [104] => Array ( [ArticleId] => 419 [Create_Time] => 2022-10-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230601082208.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002105/1002105.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002105/1002105.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002105/1002105_cover.png [JournalsId] => 4 [Title] => Potential role of resveratrol and its nano-formulation as anti-cancer agent [Abstract] => The uncontrolled and metastatic nature of cancer makes it worse and more unpredictable. Hence, many therapy and medication are used to control and treat cancer. However, apart from this, many medica [AbstractComplete] =>The uncontrolled and metastatic nature of cancer makes it worse and more unpredictable. Hence, many therapy and medication are used to control and treat cancer. However, apart from this, many medications cause various side effects. In America, nearly 8% of patients admitted to the hospital are due to side effects. Cancer is more seen in people residing in developed countries related of their lifestyle. There are various phytoconstituents molecules in which resveratrol (RSV) is the best-fitted molecule for cancer due to its significantly less adverse effect on the body. RSV inhibits the initiation and progression of cell proliferation due to the modulation of various pathways like the phosphoinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. RSV downgraded cell cycle-regulated proteins like cyclin E, cyclin D1, and proliferating cell nuclear antigen (PCNA) and induced the release of cytochrome c from the mitochondria, causing apoptosis or programmed cell death (PCD). A great benefit comes with some challenges, hence, RSV does suffer from poor solubility in water i.e. 0.05 mg/mL. It suffers from poor bioavailability due to being highly metabolized by the liver and intestine. Surprisingly, RSV metabolites also induce the metabolism of RSV. Hence, significantly less amount of RSV presented in the urine in the unchanged form. Due to some challenges like poor bioavailability, less aqueous solubility, and retention time in the body, researchers concluded to make the nanocarriers for better delivery. Adopting the technique of nano-formulations, increased topical penetration by up to 21%, improved nano-encapsulation and consequently improved bioavailability and permeability by many folds. Hence, the present review describes the complete profile of RSV and its nano-formulations for improving anti-cancer activity along with a patent survey.
[Names] => Akshay Kumar ... Dilpreet Singh [Doi] => 10.37349/etat.2022.00105 [Published] => October 31, 2022 [Viewed] => 1415 [Downloaded] => 29 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00105 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 73 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:643–658 [Recommend] => 0 [Keywords] => Resveratrol, cancer, solubility, nano-formulations, synergism [DetailTitle] => Plant Extracts as an Infinite Resource for New Anticancer Agents [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/73 [Id] => 1002105 [ris] => https://www.explorationpub.com/uploads/Article/A1002105/eb7063372ac249bac3c6ade365bb0c1c.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002105/c64af72a58473ffeb0015444768e84f6.bib [ens] => [Cited] => 12 [Cited_Time] => 2024-04-27 [CitethisArticle] => Kumar A, Kurmi BD, Singh A, Singh D. Potential role of resveratrol and its nano-formulation as anti-cancer agent. Explor Target Antitumor Ther. 2022;3:643–58. https://doi.org/10.37349/etat.2022.00105 [Jindex] => 0 [CName] => DilpreetSingh, [CEmail] => dilpreet.daman@gmail.com, [Ris_Time] => 2022-10-26 07:32:25 [Bib_Time] => 2022-10-26 07:32:25 [KeysWordContens] => Potential role of resveratrol and its nano-formulation as anti-cancer agent, Resveratrol, cancer, solubility, nano-formulations, synergism, The uncontrolled and metastatic nature of cancer makes it worse and more unpredictable. Hence, many therapy and medication are used to control and treat cancer. However, apart from this, many medications cause various side effects. In America, nearly 8% of patients admitted to the hospital are due to side effects. Cancer is more seen in people residing in developed countries related of their lifestyle. There are various phytoconstituents molecules in which resveratrol (RSV) is the best-fitted molecule for cancer due to its significantly less adverse effect on the body. RSV inhibits the initiation and progression of cell proliferation due to the modulation of various pathways like the phosphoinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. RSV downgraded cell cycle-regulated proteins like cyclin E, cyclin D1, and proliferating cell nuclear antigen (PCNA) and induced the release of cytochrome c from the mitochondria, causing apoptosis or programmed cell death (PCD). A great benefit comes with some challenges, hence, RSV does suffer from poor solubility in water i.e. 0.05 mg/mL. It suffers from poor bioavailability due to being highly metabolized by the liver and intestine. Surprisingly, RSV metabolites also induce the metabolism of RSV. Hence, significantly less amount of RSV presented in the urine in the unchanged form. Due to some challenges like poor bioavailability, less aqueous solubility, and retention time in the body, researchers concluded to make the nanocarriers for better delivery. Adopting the technique of nano-formulations, increased topical penetration by up to 21%, improved nano-encapsulation and consequently improved bioavailability and permeability by many folds. Hence, the present review describes the complete profile of RSV and its nano-formulations for improving anti-cancer activity along with a patent survey. ,Akshay Kumar ... Dilpreet Singh [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [105] => Array ( [ArticleId] => 420 [Create_Time] => 2022-10-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202211/20221101033622.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002106/1002106.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002106/1002106.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002106/1002106_cover.png [JournalsId] => 4 [Title] => Steroid utility, immunotherapy, and brain tumor management: an update on conflicting therapies [Abstract] => Steroid use is a widely accepted practice for both the treatment and prevention of tumor-induced edema, but there are many unknowns regarding their current clinical utility with modern anti-tumor th [AbstractComplete] =>Steroid use is a widely accepted practice for both the treatment and prevention of tumor-induced edema, but there are many unknowns regarding their current clinical utility with modern anti-tumor therapies. This decreases edema and relieves the symptomatic mass effect. There are clearly understood benefits and commonly accepted complications of methylprednisolone (MP) use, but the topic is recently controversial. With immunotherapy advancing, a robust immune response is crucial for full therapeutic efficacy. The immunosuppression of MP may interfere with future and current therapeutics relying on the integrity of the patient’s immune system. This further emphasizes the need for alternative agents to effectively treat tumor-induced cerebral edema. This review highlights the current clinical utility of steroids to treat brain tumor-related edema and the underlying pathophysiology. It also reviews details regarding different steroid formulations and dosing. Research available regarding concurrent steroid use with immunotherapy is detailed next, followed by alternatives to steroids and barriers to their adoption. Finally, this paper discusses pre-clinical findings and emerging treatments aimed to augment or replace steroid use.
[Names] => Matthew Goldman ... Stephan Quintin [Doi] => 10.37349/etat.2022.00106 [Published] => October 31, 2022 [Viewed] => 1002 [Downloaded] => 26 [Subject] => Review [Year] => 2022 [CiteUrl] => [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:659–675 [Recommend] => 0 [Keywords] => Steroids, tumor, management, algorithm [DetailTitle] => [DetailUrl] => [Id] => 1002106 [ris] => https://www.explorationpub.com/uploads/Article/A1002106/7d80ba92d0949350cfaefc2852d4a699.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002106/98cd7793ce5744b14ca819a9bff363e3.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Goldman M, Lucke-Wold B, Martinez-Sosa M, Katz J, Mehkri Y, Valisno J, et al. Steroid utility, immunotherapy, and brain tumor management: an update on conflicting therapies. Explor Target Antitumor Ther. 2022;3:659–75. https://doi.org/10.37349/etat.2022.00106 [Jindex] => 0 [CName] => BrandonLucke-Wold, [CEmail] => Brandon.Lucke-Wold@neurosurgery.ufl.edu, [Ris_Time] => 2022-10-26 08:51:38 [Bib_Time] => 2022-10-26 08:51:38 [KeysWordContens] => Steroid utility, immunotherapy, and brain tumor management: an update on conflicting therapies, Steroids, tumor, management, algorithm, Steroid use is a widely accepted practice for both the treatment and prevention of tumor-induced edema, but there are many unknowns regarding their current clinical utility with modern anti-tumor therapies. This decreases edema and relieves the symptomatic mass effect. There are clearly understood benefits and commonly accepted complications of methylprednisolone (MP) use, but the topic is recently controversial. With immunotherapy advancing, a robust immune response is crucial for full therapeutic efficacy. The immunosuppression of MP may interfere with future and current therapeutics relying on the integrity of the patient’s immune system. This further emphasizes the need for alternative agents to effectively treat tumor-induced cerebral edema. This review highlights the current clinical utility of steroids to treat brain tumor-related edema and the underlying pathophysiology. It also reviews details regarding different steroid formulations and dosing. Research available regarding concurrent steroid use with immunotherapy is detailed next, followed by alternatives to steroids and barriers to their adoption. Finally, this paper discusses pre-clinical findings and emerging treatments aimed to augment or replace steroid use. ,Matthew Goldman ... Stephan Quintin [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [106] => Array ( [ArticleId] => 421 [Create_Time] => 2022-10-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202210/20221031072038.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002107/1002107.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002107/1002107.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002107/1002107_cover.png [JournalsId] => 4 [Title] => Perspectives of traditional Chinese medicine to patch up immune checkpoint blockers [Abstract] => In this era of cancer immunotherapy, the response rates of immune checkpoint blockers (ICBs) are still too low and the adverse events may also be significant. Of the ways of patching up such deficit [AbstractComplete] =>In this era of cancer immunotherapy, the response rates of immune checkpoint blockers (ICBs) are still too low and the adverse events may also be significant. Of the ways of patching up such deficits, chemotherapy (ChT), especially if metronomic, seems promising, especially as immunity induced by immunogenic cell death (ICD) may be preserved. However, side effects, e.g., lymphocytopenia and interstitial pneumonitis cannot be ignored; eventually, resistance may also ensue. Vascular endothelial growth factors (VEGFs), being potent angiogenic factors, promote cancer cells’ purposeful angiogenesis rendering an extremely resistant tumor microenvironment (TME). This highly evasive and extremely resilient TME actually demands multi-agent, multi-target agents as currently in use through traditional Chinese medicine (TCM). With a good track record of 3,000 years, TCM is favored by mainland Chinese cancer patients. Although TCM had been criticized as unscientific and imprecise, recently, artificial intelligence (AI) technologies serve to elucidate the sound scientific basis and validity of TCM. Several TCM preparations having anti-VEGF actions are found; others suppress immune checkpoints. Especially, these herbs’ multi-prong approach appears to be more effective than Western medicine’s primarily monotherapy approach if one wishes to eradicate the very resistant TME. A “bonus” point is that some autoimmune-related adverse side effects of ICBs may also be reduced by TCM. Nevertheless, as the TCM experience is mostly anecdotal, robust clinical trials are mandatory. Moreover, other TCM problems, e.g., herbal batch variations and consistency and uniformity of herbal prescriptions are outstanding. Invariably, TCM prescriptions have daily variations as the practice of “syndrome differentiation” is hailed. Despite experienced TCM practitioners would refuse to give up their time-honored traditional practice, the multi-prong approach is still very attractive for the undue resilience of TME, let alone its good safety profile, ready availability, and eminent affordability. Although the passage is dark, light is now appearing at the end of the tunnel.
[Names] => Shiu Ying Tsao [Doi] => 10.37349/etat.2022.00107 [Published] => October 31, 2022 [Viewed] => 1310 [Downloaded] => 22 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00107 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 75 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:676–693 [Recommend] => 0 [Keywords] => Antiangiogenesis, hypoxia-inducible factors, multi-agent approach, traditional Chinese medicine, tumor microenvironment, vascular endothelial growth factor [DetailTitle] => Theranostic Frontiers in Neuro-oncology [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/75 [Id] => 1002107 [ris] => https://www.explorationpub.com/uploads/Article/A1002107/0f14a65ec176c8f262457879106324c2.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002107/3bc96ce2bea4c01e4805e24fc1293f6c.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Tsao SY. Perspectives of traditional Chinese medicine to patch up immune checkpoint blockers. Explor Target Antitumor Ther. 2022;3:676–93. https://doi.org/10.37349/etat.2022.00107 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-10-27 10:45:12 [Bib_Time] => 2022-10-27 10:45:12 [KeysWordContens] => Perspectives of traditional Chinese medicine to patch up immune checkpoint blockers, Antiangiogenesis, hypoxia-inducible factors, multi-agent approach, traditional Chinese medicine, tumor microenvironment, vascular endothelial growth factor, In this era of cancer immunotherapy, the response rates of immune checkpoint blockers (ICBs) are still too low and the adverse events may also be significant. Of the ways of patching up such deficits, chemotherapy (ChT), especially if metronomic, seems promising, especially as immunity induced by immunogenic cell death (ICD) may be preserved. However, side effects, e.g., lymphocytopenia and interstitial pneumonitis cannot be ignored; eventually, resistance may also ensue. Vascular endothelial growth factors (VEGFs), being potent angiogenic factors, promote cancer cells’ purposeful angiogenesis rendering an extremely resistant tumor microenvironment (TME). This highly evasive and extremely resilient TME actually demands multi-agent, multi-target agents as currently in use through traditional Chinese medicine (TCM). With a good track record of 3,000 years, TCM is favored by mainland Chinese cancer patients. Although TCM had been criticized as unscientific and imprecise, recently, artificial intelligence (AI) technologies serve to elucidate the sound scientific basis and validity of TCM. Several TCM preparations having anti-VEGF actions are found; others suppress immune checkpoints. Especially, these herbs’ multi-prong approach appears to be more effective than Western medicine’s primarily monotherapy approach if one wishes to eradicate the very resistant TME. A “bonus” point is that some autoimmune-related adverse side effects of ICBs may also be reduced by TCM. Nevertheless, as the TCM experience is mostly anecdotal, robust clinical trials are mandatory. Moreover, other TCM problems, e.g., herbal batch variations and consistency and uniformity of herbal prescriptions are outstanding. Invariably, TCM prescriptions have daily variations as the practice of “syndrome differentiation” is hailed. Despite experienced TCM practitioners would refuse to give up their time-honored traditional practice, the multi-prong approach is still very attractive for the undue resilience of TME, let alone its good safety profile, ready availability, and eminent affordability. Although the passage is dark, light is now appearing at the end of the tunnel. ,Shiu Ying Tsao [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [107] => Array ( [ArticleId] => 425 [Create_Time] => 2022-10-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202211/20221101020939.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002108/1002108.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002108/1002108.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002108/1002108_cover.png [JournalsId] => 4 [Title] => The tumor innate immune microenvironment in prostate cancer: an overview of soluble factors and cellular effectors [Abstract] => Prostate cancer (PCa) accounts as the most common non-cutaneous disease affecting males, and as the first cancer, for incidence, in male. With the introduction of the concept of immunoscore, PCa has [AbstractComplete] =>Prostate cancer (PCa) accounts as the most common non-cutaneous disease affecting males, and as the first cancer, for incidence, in male. With the introduction of the concept of immunoscore, PCa has been classified as a cold tumor, thus driving the attention in the development of strategies aimed at blocking the infiltration/activation of immunosuppressive cells, while favoring the infiltration/activation of anti-tumor immune cells. Even if immunotherapy has revolutionized the approaches to cancer therapy, there is still a window failure, due to the immune cell plasticity within PCa, that can acquire pro-tumor features, subsequent to the tumor microenvironment (TME) capability to polarize them. This review discussed selected relevant soluble factors [transforming growth factor-beta (TGFβ), interleukin-6 (IL-6), IL-10, IL-23] and cellular components of the innate immunity, as drivers of tumor progression, immunosuppression, and angiogenesis within the PCa-TME.
[Names] => Maria Teresa Palano ... Lorenzo Mortara [Doi] => 10.37349/etat.2022.00108 [Published] => October 31, 2022 [Viewed] => 1467 [Downloaded] => 58 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.000108 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 70 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:694–718 [Recommend] => 0 [Keywords] => prostate cancer, tumor immune microenvironment, innate immune cell polarization, cytokines [DetailTitle] => Cancer Immunotherapy and Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/70 [Id] => 1002108 [ris] => https://www.explorationpub.com/uploads/Article/A1002108/8d5d89abb8687cdd924faded9b35804c.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002108/104c402fa82004c2e031d0496e873338.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Palano MT, Gallazzi M, Cucchiara M, Dehò F, Capogrosso P, Bruno A, et al. The tumor innate immune microenvironment in prostate cancer: an overview of soluble factors and cellular effectors. Explor Target Antitumor Ther. 2022;3:694–718. https://doi.org/10.37349/etat.2022.00108 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-10-28 01:00:43 [Bib_Time] => 2022-10-28 01:00:43 [KeysWordContens] => The tumor innate immune microenvironment in prostate cancer: an overview of soluble factors and cellular effectors, prostate cancer, tumor immune microenvironment, innate immune cell polarization, cytokines, Prostate cancer (PCa) accounts as the most common non-cutaneous disease affecting males, and as the first cancer, for incidence, in male. With the introduction of the concept of immunoscore, PCa has been classified as a cold tumor, thus driving the attention in the development of strategies aimed at blocking the infiltration/activation of immunosuppressive cells, while favoring the infiltration/activation of anti-tumor immune cells. Even if immunotherapy has revolutionized the approaches to cancer therapy, there is still a window failure, due to the immune cell plasticity within PCa, that can acquire pro-tumor features, subsequent to the tumor microenvironment (TME) capability to polarize them. This review discussed selected relevant soluble factors [transforming growth factor-beta (TGFβ), interleukin-6 (IL-6), IL-10, IL-23] and cellular components of the innate immunity, as drivers of tumor progression, immunosuppression, and angiogenesis within the PCa-TME. ,Maria Teresa Palano ... Lorenzo Mortara [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [108] => Array ( [ArticleId] => 428 [Create_Time] => 2022-11-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202211/20221101004646.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002109/1002109.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002109/1002109.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002109/1002109_cover.png [JournalsId] => 4 [Title] => Onosma L. as a source of anticancer agents: phytochemistry to mechanistic insight [Abstract] => Onosma (O.) is a genus of perennial flowering plants in the family Boraginaceae with approximately 250 species widely dispersed in temperate, tropical, and subtropical areas. It is traditionally use [AbstractComplete] =>Onosma (O.) is a genus of perennial flowering plants in the family Boraginaceae with approximately 250 species widely dispersed in temperate, tropical, and subtropical areas. It is traditionally used to treat rheumatism, fever, asthma, stomach irritation, and inflammatory ailments. The bioactive constituents present in the genus O. include benzoquinones, naphthazarins, alkaloids, phenolic, naphthoquinones, and flavonoids whereas shikonins and onosmins are the most significant. The review compiled contemporary research on O. L., including its distribution, morphology, traditional applications, phytochemistry, ethnopharmacology, and toxicology. This review also highlights a few critical challenges and possible future directions for O. L. research. Modern research has demonstrated a wide range of pharmacological effects of different species of O. L., including anti-diabetic, anticancer, anti-inflammatory, and cardiovascular protective. However, the studies on the O. genus are still not fully explored, therefore, researchers need to discover novel products with their toxicity studies, molecular mechanism, and associated side effects. Future exploration of potent constituents from this genus and clinical trials are required to explore its pharmacological importance.
[Names] => Ajay Kumar ... Satwinderjeet Kaur [Doi] => 10.37349/etat.2022.00109 [Published] => October 31, 2022 [Viewed] => 1152 [Downloaded] => 50 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00109 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 73 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:719–733 [Recommend] => 0 [Keywords] => Alkaloids, anti-cancer, anti-inflammatory, Boraginaceae ethnopharmacological, naphthoquinones, shikonin [DetailTitle] => Plant Extracts as an Infinite Resource for New Anticancer Agents [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/73 [Id] => 1002109 [ris] => https://www.explorationpub.com/uploads/Article/A1002109/4325b5903ab0d39d1716cc27e65d322f.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002109/be435b4182d9a59d3b8351e00cc5c833.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Kumar A, Attri S, Kaur S, Tuli HS, Saini RV, Saini AK, et al. Onosma L. as a source of anticancer agents: phytochemistry to mechanistic insight. Explor Target Antitumor Ther. 2022;3:719–33. https://doi.org/10.37349/etat.2022.00109 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-10-31 03:38:54 [Bib_Time] => 2022-10-31 03:38:54 [KeysWordContens] => Onosma L. as a source of anticancer agents: phytochemistry to mechanistic insight, Alkaloids, anti-cancer, anti-inflammatory, Boraginaceae ethnopharmacological, naphthoquinones, shikonin, Onosma (O.) is a genus of perennial flowering plants in the family Boraginaceae with approximately 250 species widely dispersed in temperate, tropical, and subtropical areas. It is traditionally used to treat rheumatism, fever, asthma, stomach irritation, and inflammatory ailments. The bioactive constituents present in the genus O. include benzoquinones, naphthazarins, alkaloids, phenolic, naphthoquinones, and flavonoids whereas shikonins and onosmins are the most significant. The review compiled contemporary research on O. L., including its distribution, morphology, traditional applications, phytochemistry, ethnopharmacology, and toxicology. This review also highlights a few critical challenges and possible future directions for O. L. research. Modern research has demonstrated a wide range of pharmacological effects of different species of O. L., including anti-diabetic, anticancer, anti-inflammatory, and cardiovascular protective. However, the studies on the O. genus are still not fully explored, therefore, researchers need to discover novel products with their toxicity studies, molecular mechanism, and associated side effects. Future exploration of potent constituents from this genus and clinical trials are required to explore its pharmacological importance. ,Ajay Kumar ... Satwinderjeet Kaur [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [109] => Array ( [ArticleId] => 437 [Create_Time] => 2022-12-13 [zipUrl] => https://www.explorationpub.com/uploads/zip/202301/20230106071634.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002110/1002110.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002110/1002110.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002110/1002110_cover.png [JournalsId] => 4 [Title] => Diffusion-weighted imaging and apparent diffusion coefficient mapping of head and neck lymph node metastasis: a systematic review [Abstract] => Aim: Head and neck squamous cell cancer (HNSCC) is the ninth most common tumor worldwide. Neck lymph node (LN) status is the major indicator of prognosis in all head and neck cancers, and the early detection of LN involvement is crucial in terms of therapy and prognosis. Diffusion-weighted imaging (DWI) is a non-invasive imaging technique used in magnetic resonance imaging (MRI) to characterize tissues based on the displacement motion of water molecules. This review aims to provide an overview of the current literature concerning quantitative diffusion imaging for LN staging in patients with HNSCC. Methods: This systematic review performed a literature search on the PubMed database (https://pubmed.ncbi.nlm.nih.gov/) for all relevant, peer-reviewed literature on the subject following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) criteria, using the keywords: DWI, MRI, head and neck, staging, lymph node. Results: After excluding reviews, meta-analyses, case reports, and bibliometric studies, 18 relevant papers out of the 567 retrieved were selected for analysis. Conclusions: DWI improves the diagnosis, treatment planning, treatment response evaluation, and overall management of patients affected by HNSCC. More robust data to clarify the role of apparent diffusion coefficient (ADC) and DWI parameters are needed to develop models for prognosis and prediction in HNSCC cancer using MRI. [AbstractComplete] =>Head and neck squamous cell cancer (HNSCC) is the ninth most common tumor worldwide. Neck lymph node (LN) status is the major indicator of prognosis in all head and neck cancers, and the early detection of LN involvement is crucial in terms of therapy and prognosis. Diffusion-weighted imaging (DWI) is a non- invasive imaging technique used in magnetic resonance imaging (MRI) to characterize tissues based on the displacement motion of water molecules. This review aims to provide an overview of the current literature concerning quantitative diffusion imaging for LN staging in patients with HNSCC.
This systematic review performed a literature search on the PubMed database (https://pubmed.ncbi.nlm.nih.gov/) for all relevant, peer-reviewed literature on the subject following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) criteria, using the keywords: DWI, MRI, head and neck, staging, lymph node.
After excluding reviews, meta-analyses, case reports, and bibliometric studies, 18 relevant papers out of the 567 retrieved were selected for analysis.
DWI improves the diagnosis, treatment planning, treatment response evaluation, and overall management of patients affected by HNSCC. More robust data to clarify the role of apparent diffusion coefficient (ADC) and DWI parameters are needed to develop models for prognosis and prediction in HNSCC cancer using MRI.
Major advances in cancer treatment have emerged with the introduction of immunotherapies using blocking antibodies that target T-cell inhibitory receptors, such as programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), known as immune checkpoints. However, most cancer patients do not respond to immune checkpoint blockade (ICB) therapies, suggesting the development of resistance mechanisms associated with either an insufficient number of preexisting tumor-specific T-cell precursors and/or inappropriate T-cell reactivation. To broaden clinical benefit, anti-PD-1/PD-1 ligand (PD-L1) neutralizing antibodies have been combined with therapeutic cancer vaccines based on non-mutant and/or mutant tumor antigens, to stimulate and expand tumor-specific T lymphocytes. Although these combination treatments achieve the expected goal in some patients, relapse linked to alterations in antigen presentation machinery (APM) of cancer cells often occurs leading to tumor escape from CD8 T-cell immunity. Remarkably, an alternative antigenic peptide repertoire, referred to as T-cell epitopes associated with impaired peptide processing (TEIPP), arises on these malignant cells with altered APM. TEIPP are derived from ubiquitous non-mutant self-proteins and represent a unique resource to target immune-edited tumors that have acquired resistance to cytotoxic T lymphocytes (CTLs) related to defects in transporter associated with antigen processing (TAP) and possibly also to ICB. The present review discusses tumor-associated antigens (TAAs) and mutant neoantigens and their use as targets in peptide- and RNA-based therapeutic cancer vaccines. Finally, this paper highlights TEIPP as a promising immunogenic non-mutant neoantigen candidates for active cancer immunotherapy and combination with TAA and mutant neoantigens. Combining these polyepitope cancer vaccines with ICB would broaden T-cell specificity and reinvigorate exhausted antitumor CTL, resulting in the eradication of all types of neoplastic cells, including immune-escaped subtypes.
[Names] => Mohamad Omar Ashi ... Stéphanie Corgnac [Doi] => 10.37349/etat.2022.00111 [Published] => December 22, 2022 [Viewed] => 1312 [Downloaded] => 55 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00111 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 70 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:746–762 [Recommend] => 0 [Keywords] => Cancer immunotherapy, therapeutic peptide vaccine, messenger RNA vaccine, tumor-associated antigen, neoantigen, T-cell epitopes associated with impaired peptide processing [DetailTitle] => Cancer Immunotherapy and Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/70 [Id] => 1002111 [ris] => https://www.explorationpub.com/uploads/Article/A1002111/4e0405b2304053cb5c24bd3a824b4d0d.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002111/0620b2723a05befda740269cadb2277c.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Ashi MO, Mami-Chouaib F, Corgnac S. Mutant and non-mutant neoantigen-based cancer vaccines: recent advances and future promises. Explor Target Antitumor Ther. 2022;3:746–62. https://doi.org/10.37349/etat.2022.00111 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-12-12 02:49:35 [Bib_Time] => 2022-12-12 02:49:35 [KeysWordContens] => Mutant and non-mutant neoantigen-based cancer vaccines: recent advances and future promises, Cancer immunotherapy, therapeutic peptide vaccine, messenger RNA vaccine, tumor-associated antigen, neoantigen, T-cell epitopes associated with impaired peptide processing, Major advances in cancer treatment have emerged with the introduction of immunotherapies using blocking antibodies that target T-cell inhibitory receptors, such as programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), known as immune checkpoints. However, most cancer patients do not respond to immune checkpoint blockade (ICB) therapies, suggesting the development of resistance mechanisms associated with either an insufficient number of preexisting tumor-specific T-cell precursors and/or inappropriate T-cell reactivation. To broaden clinical benefit, anti-PD-1/PD-1 ligand (PD-L1) neutralizing antibodies have been combined with therapeutic cancer vaccines based on non-mutant and/or mutant tumor antigens, to stimulate and expand tumor-specific T lymphocytes. Although these combination treatments achieve the expected goal in some patients, relapse linked to alterations in antigen presentation machinery (APM) of cancer cells often occurs leading to tumor escape from CD8 T-cell immunity. Remarkably, an alternative antigenic peptide repertoire, referred to as T-cell epitopes associated with impaired peptide processing (TEIPP), arises on these malignant cells with altered APM. TEIPP are derived from ubiquitous non-mutant self-proteins and represent a unique resource to target immune-edited tumors that have acquired resistance to cytotoxic T lymphocytes (CTLs) related to defects in transporter associated with antigen processing (TAP) and possibly also to ICB. The present review discusses tumor-associated antigens (TAAs) and mutant neoantigens and their use as targets in peptide- and RNA-based therapeutic cancer vaccines. Finally, this paper highlights TEIPP as a promising immunogenic non-mutant neoantigen candidates for active cancer immunotherapy and combination with TAA and mutant neoantigens. Combining these polyepitope cancer vaccines with ICB would broaden T-cell specificity and reinvigorate exhausted antitumor CTL, resulting in the eradication of all types of neoplastic cells, including immune-escaped subtypes. ,Mohamad Omar Ashi ... Stéphanie Corgnac [PublishedText] => Published [IsEdit] => 0 [AccountId] => 38 [Zh] => 1 ) [111] => Array ( [ArticleId] => 1182 [Create_Time] => 2024-04-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240424023712.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002220/1002220.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002220/1002220.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002220/1002220_cover.png [JournalsId] => 4 [Title] => Magnetite nanoparticles: an emerging adjunctive tool for the improvement of cancer immunotherapy [Abstract] => Cancer immunotherapy has emerged as a groundbreaking field, offering promising and transformative tools for oncological research and treatment. However, it faces several limitations, including varia [AbstractComplete] =>Cancer immunotherapy has emerged as a groundbreaking field, offering promising and transformative tools for oncological research and treatment. However, it faces several limitations, including variations in cancer types, dependence on the tumor microenvironments (TMEs), immune cell exhaustion, and adverse reactions. Magnetic nanoparticles, particularly magnetite nanoparticles (MNPs), with established pharmacodynamics and pharmacokinetics for clinical use, hold great promise in this context and are now being explored for therapeutic aims. Numerous preclinical studies have illustrated their efficacy in enhancing immunotherapy through various strategies, such as modulating leukocyte functions, creating favorable TMEs for cytotoxic T lymphocytes, combining with monoclonal antibodies, and stimulating the immune response via magnetic hyperthermia (MHT) treatment (Front Immunol. 2021;12:701485. doi: 10.3389/fimmu.2021.701485). However, the current clinical trials of MNPs are mostly for diagnostic aims and as a tool for generating hyperthermia for tumor ablation. With concerns about the adverse effects of MNPs in the in vivo systems, clinical translation and clinical study of MNP-boosted immunotherapy remains limited. The lack of extensive clinical investigations poses a current barrier to patient application. Urgent efforts are needed to ascertain both the efficacy of MNP-enhanced immunotherapy and its safety profile in combination therapy. This article reviews the roles, potential, and challenges of using MNPs in advancing cancer immunotherapy. The application of MNPs in boosting immunotherapy, and its perspective role in research and development is also discussed.
[Names] => Phoomipat Jungcharoen ... Charupong Saengboonmee [Doi] => 10.37349/etat.2024.00220 [Published] => April 23, 2024 [Viewed] => 140 [Downloaded] => 12 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00220 [Inline] => 1 [Type] => 0 [Issue] => [Topic] => 175 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:316–331 [Recommend] => 0 [Keywords] => Cancer, magnetic iron oxide nanoparticles, immunotherapy, tumor microenvironment [DetailTitle] => Novel Strategies and Targets for Immunotherapy of Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/175 [Id] => 1002220 [ris] => https://www.explorationpub.com/uploads/Article/A1002220/9f0057f9a71b3f0950256311c2af6b88.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002220/4be870aeed35d6579877fad6ac79e4a6.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Jungcharoen P, Thivakorakot K, Thientanukij N, Kosachunhanun N, Vichapattana C, Panaampon J, et al. Magnetite nanoparticles: an emerging adjunctive tool for the improvement of cancer immunotherapy. Explor Target Antitumor Ther. 2024;5:316–31. https://doi.org/10.37349/etat.2024.00220 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-24 02:37:12 [Bib_Time] => 2024-04-24 02:37:12 [KeysWordContens] => Magnetite nanoparticles: an emerging adjunctive tool for the improvement of cancer immunotherapy, Cancer, magnetic iron oxide nanoparticles, immunotherapy, tumor microenvironment, Cancer immunotherapy has emerged as a groundbreaking field, offering promising and transformative tools for oncological research and treatment. However, it faces several limitations, including variations in cancer types, dependence on the tumor microenvironments (TMEs), immune cell exhaustion, and adverse reactions. Magnetic nanoparticles, particularly magnetite nanoparticles (MNPs), with established pharmacodynamics and pharmacokinetics for clinical use, hold great promise in this context and are now being explored for therapeutic aims. Numerous preclinical studies have illustrated their efficacy in enhancing immunotherapy through various strategies, such as modulating leukocyte functions, creating favorable TMEs for cytotoxic T lymphocytes, combining with monoclonal antibodies, and stimulating the immune response via magnetic hyperthermia (MHT) treatment (Front Immunol. 2021;12:701485. doi: 10.3389/fimmu.2021.701485). However, the current clinical trials of MNPs are mostly for diagnostic aims and as a tool for generating hyperthermia for tumor ablation. With concerns about the adverse effects of MNPs in the in vivo systems, clinical translation and clinical study of MNP-boosted immunotherapy remains limited. The lack of extensive clinical investigations poses a current barrier to patient application. Urgent efforts are needed to ascertain both the efficacy of MNP-enhanced immunotherapy and its safety profile in combination therapy. This article reviews the roles, potential, and challenges of using MNPs in advancing cancer immunotherapy. The application of MNPs in boosting immunotherapy, and its perspective role in research and development is also discussed. ,Phoomipat Jungcharoen ... Charupong Saengboonmee [PublishedText] => Published [IsEdit] => 0 [AccountId] => 77 [Zh] => 1 ) [112] => Array ( [ArticleId] => 442 [Create_Time] => 2022-12-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202305/20230522055447.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002112/1002112.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002112/1002112.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002112/1002112_cover.png [JournalsId] => 4 [Title] => Antibody-drug conjugates for lymphoma patients: preclinical and clinical evidences [Abstract] => Antibody-drug conjugates (ADCs) are a recent, revolutionary approach for malignancies treatment, designed to provide superior efficacy and specific targeting of tumor cells, compared to systemic cyt [AbstractComplete] =>Antibody-drug conjugates (ADCs) are a recent, revolutionary approach for malignancies treatment, designed to provide superior efficacy and specific targeting of tumor cells, compared to systemic cytotoxic chemotherapy. Their structure combines highly potent anti-cancer drugs (payloads or warheads) and monoclonal antibodies (Abs), specific for a tumor-associated antigen, via a chemical linker. Because the sensitive targeting capabilities of monoclonal Abs allow the direct delivery of cytotoxic payloads to tumor cells, these agents leave healthy cells unharmed, reducing toxicity. Different ADCs have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of a wide range of malignant conditions, both as monotherapy and in combination with chemotherapy, including for lymphoma patients. Over 100 ADCs are under preclinical and clinical investigation worldwide. This paper it provides an overview of approved and promising ADCs in clinical development for the treatment of lymphoma. Each component of the ADC design, their mechanism of action, and the highlights of their clinical development progress are discussed.
[Names] => Marilia Barreca ... Francesco Bertoni [Doi] => 10.37349/etat.2022.00112 [Published] => December 26, 2022 [Viewed] => 1744 [Downloaded] => 61 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00112 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 45 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:763–794 [Recommend] => 0 [Keywords] => Antibody-drug conjugate, cytotoxic payload, monoclonal antibody, linkers, lymphoma [DetailTitle] => Antibody-Drug Conjugates [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/45 [Id] => 1002112 [ris] => https://www.explorationpub.com/uploads/Article/A1002112/d01787cfc241c1351085c371bd4243e5.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002112/cf054a432b92f39748082a9c0a8f96ad.bib [ens] => [Cited] => 8 [Cited_Time] => 2024-04-27 [CitethisArticle] => Barreca M, Lang N, Tarantelli C, Spriano F, Barraja P, Bertoni F. Antibody-drug conjugates for lymphoma patients: preclinical and clinical evidences. Explor Target Antitumor Ther. 2022;3:763–94. https://doi.org/10.37349/etat.2022.00112 [Jindex] => 0 [CName] => FrancescoBertoni, [CEmail] => francesco.bertoni@ior.usi.ch, [Ris_Time] => 2022-12-27 03:13:57 [Bib_Time] => 2022-12-27 03:13:57 [KeysWordContens] => Antibody-drug conjugates for lymphoma patients: preclinical and clinical evidences, Antibody-drug conjugate, cytotoxic payload, monoclonal antibody, linkers, lymphoma, Antibody-drug conjugates (ADCs) are a recent, revolutionary approach for malignancies treatment, designed to provide superior efficacy and specific targeting of tumor cells, compared to systemic cytotoxic chemotherapy. Their structure combines highly potent anti-cancer drugs (payloads or warheads) and monoclonal antibodies (Abs), specific for a tumor-associated antigen, via a chemical linker. Because the sensitive targeting capabilities of monoclonal Abs allow the direct delivery of cytotoxic payloads to tumor cells, these agents leave healthy cells unharmed, reducing toxicity. Different ADCs have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of a wide range of malignant conditions, both as monotherapy and in combination with chemotherapy, including for lymphoma patients. Over 100 ADCs are under preclinical and clinical investigation worldwide. This paper it provides an overview of approved and promising ADCs in clinical development for the treatment of lymphoma. Each component of the ADC design, their mechanism of action, and the highlights of their clinical development progress are discussed. ,Marilia Barreca ... Francesco Bertoni [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 1 ) [113] => Array ( [ArticleId] => 443 [Create_Time] => 2022-12-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202305/20230522081731.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002113/1002113.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002113/1002113.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002113/1002113_cover.png [JournalsId] => 4 [Title] => Artificial intelligence in breast cancer imaging: risk stratification, lesion detection and classification, treatment planning and prognosis—a narrative review [Abstract] => The advent of artificial intelligence (AI) represents a real game changer in today’s landscape of breast cancer imaging. Several innovative AI-based tools have been developed and validated in recent years that promise to accelerate the goal of real patient-tailored management. Numerous studies confirm that proper integration of AI into existing clinical workflows could bring significant benefits to women, radiologists, and healthcare systems. The AI-based approach has proved particularly useful for developing new risk prediction models that integrate multi-data streams for planning individualized screening protocols. [AbstractComplete] =>The advent of artificial intelligence (AI) represents a real game changer in today’s landscape of breast cancer imaging. Several innovative AI-based tools have been developed and validated in recent years that promise to accelerate the goal of real patient-tailored management. Numerous studies confirm that proper integration of AI into existing clinical workflows could bring significant benefits to women, radiologists, and healthcare systems. The AI-based approach has proved particularly useful for developing new risk prediction models that integrate multi-data streams for planning individualized screening protocols. Furthermore, AI models could help radiologists in the pre-screening and lesion detection phase, increasing diagnostic accuracy, while reducing workload and complications related to overdiagnosis. Radiomics and radiogenomics approaches could extrapolate the so-called imaging signature of the tumor to plan a targeted treatment. The main challenges to the development of AI tools are the huge amounts of high-quality data required to train and validate these models and the need for a multidisciplinary team with solid machine-learning skills. The purpose of this article is to present a summary of the most important AI applications in breast cancer imaging, analyzing possible challenges and new perspectives related to the widespread adoption of these new tools.
[Names] => Maurizio Cè ... Michaela Cellina [Doi] => 10.37349/etat.2022.00113 [Published] => December 27, 2022 [Viewed] => 1718 [Downloaded] => 60 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00113 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 88 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:795–816 [Recommend] => 0 [Keywords] => Breast cancer imaging, artificial intelligence, machine learning, computer-aided detection, mammogram, digital breast tomosynthesis, magnetic resonance imaging [DetailTitle] => Artificial Intelligence for Precision Oncology [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/88 [Id] => 1002113 [ris] => https://www.explorationpub.com/uploads/Article/A1002113/1c9006c35a49ab38aac9093d45847b0b.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002113/8990d6f3adf5e997cad7929ca3848378.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-27 [CitethisArticle] => Cè M, Caloro E, Pellegrino ME, Basile M, Sorce A, Fazzini D, et al. Artificial intelligence in breast cancer imaging: risk stratification, lesion detection and classification, treatment planning and prognosis—a narrative review. Explor Target Antitumor Ther. 2022;3:795–816. https://doi.org/10.37349/etat.2022.00113 [Jindex] => 0 [CName] => MaurizioCè, [CEmail] => maurizioce.md1@gmail.com, [Ris_Time] => 2022-12-26 06:48:31 [Bib_Time] => 2022-12-26 06:48:31 [KeysWordContens] => Artificial intelligence in breast cancer imaging: risk stratification, lesion detection and classification, treatment planning and prognosis—a narrative review, Breast cancer imaging, artificial intelligence, machine learning, computer-aided detection, mammogram, digital breast tomosynthesis, magnetic resonance imaging, The advent of artificial intelligence (AI) represents a real game changer in today’s landscape of breast cancer imaging. Several innovative AI-based tools have been developed and validated in recent years that promise to accelerate the goal of real patient-tailored management. Numerous studies confirm that proper integration of AI into existing clinical workflows could bring significant benefits to women, radiologists, and healthcare systems. The AI-based approach has proved particularly useful for developing new risk prediction models that integrate multi-data streams for planning individualized screening protocols. Furthermore, AI models could help radiologists in the pre-screening and lesion detection phase, increasing diagnostic accuracy, while reducing workload and complications related to overdiagnosis. Radiomics and radiogenomics approaches could extrapolate the so-called imaging signature of the tumor to plan a targeted treatment. The main challenges to the development of AI tools are the huge amounts of high-quality data required to train and validate these models and the need for a multidisciplinary team with solid machine-learning skills. The purpose of this article is to present a summary of the most important AI applications in breast cancer imaging, analyzing possible challenges and new perspectives related to the widespread adoption of these new tools. ,Maurizio Cè ... Michaela Cellina [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [114] => Array ( [ArticleId] => 444 [Create_Time] => 2022-12-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202212/20221227085637.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002114/1002114.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002114/1002114.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002114/1002114-cover.png [JournalsId] => 4 [Title] => Encouraging probiotics for the prevention and treatment of immune-related adverse events in novel immunotherapies against malignant glioma [Abstract] => Among the malignant tumors in the central nervous system (CNS), glioma is the most challenging tumor to the public society, which accounts for the majority of intracranial malignant tumors with impa [AbstractComplete] =>Among the malignant tumors in the central nervous system (CNS), glioma is the most challenging tumor to the public society, which accounts for the majority of intracranial malignant tumors with impaired brain function. In general, conventional therapies are still unable to provide an effective cure. However, novel immunotherapies have changed the treatment scene giving patients a greater potential to attain long term survival, improved quality of life. Having shown favorable results in solid tumors, those therapies are now at a cancer research hotspot, which could even shrink the growth of glioma cells without causing severe complications. However, it is important to recognize that the therapy may be occasionally associated with noteworthy adverse action called immune-related adverse events (IRAEs) which have emerged as a potential limitation of the therapy. Multiple classes of mediators have been developed to enhance the ability of immune system to target malignant tumors including glioma but may also be associated with the IRAEs. In addition, it is probable that it would take long time after the therapy to exhibit severe immune-related disorders. Gut microbiota could play an integral role in optimal immune development and/or appropriate function for the cancer therapy, which is a vital component of the multidirectional communication between immune system, brain, and gut, also known as gut-brain-immune axis. Here, we show the potential effects of the gut-brain-immune axis based on an “engram theory” for the innovative treatment of IRAEs.
[Names] => Sayuri Yoshikawa ... Satoru Matsuda [Doi] => 10.37349/etat.2022.00114 [Published] => December 27, 2022 [Viewed] => 2934 [Downloaded] => 1314 [Subject] => Perspective [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00114 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 75 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:817–827 [Recommend] => 0 [Keywords] => Glioma, oncolytic virus therapy, immune-related adverse events, gut microbiota, gut-brain-immune axis, engram, immune-related disorders, reactive oxygen species [DetailTitle] => Theranostic Frontiers in Neuro-Oncology [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/75 [Id] => 1002114 [ris] => https://www.explorationpub.com/uploads/Article/A1002114/f61259982958d071e884c176ac868820.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002114/d4fd656232da52633d9e48451de70d62.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-27 [CitethisArticle] => Yoshikawa S, Taniguchi K, Sawamura H, Ikeda Y, Tsuji A, Matsuda S. Encouraging probiotics for the prevention and treatment of immune-related adverse events in novel immunotherapies against malignant glioma. Explor Target Antitumor Ther. 2022;3:817–27. https://doi.org/10.37349/etat.2022.00114 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-12-26 07:43:53 [Bib_Time] => 2022-12-26 07:43:53 [KeysWordContens] => Encouraging probiotics for the prevention and treatment of immune-related adverse events in novel immunotherapies against malignant glioma, Glioma, oncolytic virus therapy, immune-related adverse events, gut microbiota, gut-brain-immune axis, engram, immune-related disorders, reactive oxygen species, Among the malignant tumors in the central nervous system (CNS), glioma is the most challenging tumor to the public society, which accounts for the majority of intracranial malignant tumors with impaired brain function. In general, conventional therapies are still unable to provide an effective cure. However, novel immunotherapies have changed the treatment scene giving patients a greater potential to attain long term survival, improved quality of life. Having shown favorable results in solid tumors, those therapies are now at a cancer research hotspot, which could even shrink the growth of glioma cells without causing severe complications. However, it is important to recognize that the therapy may be occasionally associated with noteworthy adverse action called immune-related adverse events (IRAEs) which have emerged as a potential limitation of the therapy. Multiple classes of mediators have been developed to enhance the ability of immune system to target malignant tumors including glioma but may also be associated with the IRAEs. In addition, it is probable that it would take long time after the therapy to exhibit severe immune-related disorders. Gut microbiota could play an integral role in optimal immune development and/or appropriate function for the cancer therapy, which is a vital component of the multidirectional communication between immune system, brain, and gut, also known as gut-brain-immune axis. Here, we show the potential effects of the gut-brain-immune axis based on an “engram theory” for the innovative treatment of IRAEs. ,Sayuri Yoshikawa ... Satoru Matsuda [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [115] => Array ( [ArticleId] => 446 [Create_Time] => 2022-12-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202212/20221229065822.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002115/1002115.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002115/1002115.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002115/1002115-Cover.png [JournalsId] => 4 [Title] => Dendritic cell-targeting chemokines inhibit colorectal cancer progression [Abstract] => Aim: Recent progress in cancer immunotherapy has shown its promise and prompted researchers to develop novel therapeutic strategies. Dendritic cells (DCs) are professional antigen-presenting cell [AbstractComplete] =>Recent progress in cancer immunotherapy has shown its promise and prompted researchers to develop novel therapeutic strategies. Dendritic cells (DCs) are professional antigen-presenting cells crucial for initiating adaptive anti-tumor immunity, therefore a promising target for cancer treatment. Here, anti-tumor activities of DC-targeting chemokines were explored in murine colorectal tumor models.
The correlation of chemokine messenger RNA (mRNA) expression with DC markers was analyzed using The Cancer Genome Atlas (TCGA) dataset. Murine colorectal tumor cell lines (CT26 and MC38) stably overexpressing mouse C-C motif chemokine ligand 3 (CCL3), CCL19, CCL21, and X-C motif chemokine ligand 1 (XCL1) were established by lentiviral transduction. The effect of chemokines on tumor cell proliferation/survival was evaluated in vitro by cell counting kit-8 (CCK-8) assay and colony formation assay. Syngeneic subcutaneous tumor models were used to study the effects of these chemokines on tumor growth. Ki-67 expression in tumors was examined by immunohistochemistry. Immune cells in the tumor microenvironment (TME) and lymph nodes were analyzed by flow cytometry.
Expression of the four chemokines was positively correlated with the two DC markers [integrin alpha X (ITGAX) and CLEC9A] in human colorectal tumor samples. Tumoral overexpression of DC-targeting chemokines had little or no effect on tumor cell proliferation/survival in vitro while significantly suppressing tumor growth in vivo. Fluorescence-activated cell sorting (FACS) analysis showed that CCL19, CCL21, and XCL1 boosted the ratios of DCs and T cells in CD45+ leukocytes while CCL3 increased the percentage of CD45+ leukocytes in total cells in MC38 tumor. XCL1 had an additional positive effect on antigen uptake by DCs in the TME and antigen transfer to tumor-draining lymph nodes.
CCL3, CCL19, CCL21, and XCL1 exhibited potent anti-tumor activities in vivo, although they might differentially regulate immune cells in the TME and antigen transfer to lymph nodes.
The onset and development of breast cancer in postmenopausal women are associated with closely related individual-dependent factors, including weight gain and high levels of circulating androgens. Adipose tissue is the most peripheral site of aromatase enzyme synthesis; therefore, the excessive accumulation of visceral fat results in increased androgens aromatization and estradiol production that provides the microenvironment favorable to tumorigenesis in mammary epithelial cells expressing estrogen receptors (ERs). Moreover, to meet the increased requirement of cholesterol for cell membrane assembly and the production of steroid hormones to sustain their proliferation, ER-positive cells activate de novo cholesterol biosynthesis and subsequent steroidogenesis. Several approaches have been followed to neutralize the de novo cholesterol synthesis, including specific enzyme inhibitors, statins, and, more recently, metformin. Cumulating evidence indicated that inhibiting cholesterol biosynthesis by statins and metformin may be a promising therapeutic strategy to block breast cancer progression. Unlike antiestrogens and aromatase inhibitors (AIs) which compete for binding to ER and inhibit androgens aromatization, respectively, statins block the production of mevalonic acid by inhibiting the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and metformin hampers the activation of the sterol regulatory element-binding protein 2 (SREBP2) transcription factor, thus inhibiting the synthesis of several enzymes involved in cholesterol biosynthesis. Noteworthy, statins and metformin not only improve the prognosis of overweight patients with ER-positive cancer but also improve the prognosis of patients with triple-negative breast cancer, the aggressive tumor subtype that lacks, at present, specific therapy.
[Names] => Danila Coradini [Doi] => 10.37349/etat.2022.00116 [Published] => December 28, 2022 [Viewed] => 883 [Downloaded] => 22 [Subject] => Commentary [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00116 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:841–852 [Recommend] => 0 [Keywords] => Breast cancer, cholesterol biosynthesis, statins, metformin [DetailTitle] => [DetailUrl] => [Id] => 1002116 [ris] => https://www.explorationpub.com/uploads/Article/A1002116/037669d31b5bc4b07f1b7fef8d597350.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002116/04892e1ea60bbb6f1afd32d5099055b6.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Coradini D. De novo cholesterol biosynthesis: an additional therapeutic target for the treatment of postmenopausal breast cancer with excessive adipose tissue. Explor Target Antitumor Ther. 2022;3:841–52. https://doi.org/10.37349/etat.2022.00116 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-12-28 05:31:18 [Bib_Time] => 2022-12-28 05:31:18 [KeysWordContens] => De novo cholesterol biosynthesis: an additional therapeutic target for the treatment of postmenopausal breast cancer with excessive adipose tissue, Breast cancer, cholesterol biosynthesis, statins, metformin, The onset and development of breast cancer in postmenopausal women are associated with closely related individual-dependent factors, including weight gain and high levels of circulating androgens. Adipose tissue is the most peripheral site of aromatase enzyme synthesis; therefore, the excessive accumulation of visceral fat results in increased androgens aromatization and estradiol production that provides the microenvironment favorable to tumorigenesis in mammary epithelial cells expressing estrogen receptors (ERs). Moreover, to meet the increased requirement of cholesterol for cell membrane assembly and the production of steroid hormones to sustain their proliferation, ER-positive cells activate de novo cholesterol biosynthesis and subsequent steroidogenesis. Several approaches have been followed to neutralize the de novo cholesterol synthesis, including specific enzyme inhibitors, statins, and, more recently, metformin. Cumulating evidence indicated that inhibiting cholesterol biosynthesis by statins and metformin may be a promising therapeutic strategy to block breast cancer progression. Unlike antiestrogens and aromatase inhibitors (AIs) which compete for binding to ER and inhibit androgens aromatization, respectively, statins block the production of mevalonic acid by inhibiting the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and metformin hampers the activation of the sterol regulatory element-binding protein 2 (SREBP2) transcription factor, thus inhibiting the synthesis of several enzymes involved in cholesterol biosynthesis. Noteworthy, statins and metformin not only improve the prognosis of overweight patients with ER-positive cancer but also improve the prognosis of patients with triple-negative breast cancer, the aggressive tumor subtype that lacks, at present, specific therapy. ,Danila Coradini [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 1 ) [117] => Array ( [ArticleId] => 456 [Create_Time] => 2022-12-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202301/20230106102233.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002117/1002117.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002117/1002117.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002117/1002117_cover.png [JournalsId] => 4 [Title] => Evaluating immune response in vitro in a relevant microenvironment: a high-throughput microfluidic model for clinical screening [Abstract] => Aim: Functional screening of new pharmaceutical compounds requires clinically relevant models to monitor essential cellular and immune responses during cancer progression, with or without treatment. Beyond survival, the emergence of resistant tumor cell clones should also be considered, including specific properties related to plasticity, such as invasiveness, stemness, escape from programmed cell death, and immune response. Numerous pathways are involved in these processes. Defining the relevant ones in the context of a specific tumor type will be key to designing an appropriate combination of inhibitors. However, the diversity and potential redundancy of these pathways remain a challenge for therapy. Methods: A new microfluidic device developed by Okomera was dedicated to the screening of drug treatment for breast cancer. This microchip includes 150 droplet-trapping microwells, offering multi-chip settings and multiple treatment choices. Results: After validating the system with established cell lines and a panel of drugs used clinically at Gustave Roussy, preclinical experiments were initiated including patient-derived xenograft (PDX) and primary tumor cells-derived tumoroids with the collaboration of Gustave Roussy clinicians. Tumor-isolated lymphocytes were also added to the tumoroids, using secondary droplets in proof-of-concept experiments. Conclusions: These results show the relevance of the methodology for screening large numbers of drugs, a wide range of doses, and multiple drug combinations. This methodology will be used for two purposes: 1) new drug screening from the compound library, using the high throughput potential of the chip; and 2) pre-clinical assay for a two-weeks response for personalized medicine, allowing evaluation of drug combinations to flag an optimized treatment with potential clinical application. [AbstractComplete] =>Functional screening of new pharmaceutical compounds requires clinically relevant models to monitor essential cellular and immune responses during cancer progression, with or without treatment. Beyond survival, the emergence of resistant tumor cell clones should also be considered, including specific properties related to plasticity, such as invasiveness, stemness, escape from programmed cell death, and immune response. Numerous pathways are involved in these processes. Defining the relevant ones in the context of a specific tumor type will be key to designing an appropriate combination of inhibitors. However, the diversity and potential redundancy of these pathways remain a challenge for therapy.
A new microfluidic device developed by Okomera was dedicated to the screening of drug treatment for breast cancer. This microchip includes 150 droplet-trapping microwells, offering multi-chip settings and multiple treatment choices.
After validating the system with established cell lines and a panel of drugs used clinically at Gustave Roussy, preclinical experiments were initiated including patient-derived xenograft (PDX) and primary tumor cells-derived tumoroids with the collaboration of Gustave Roussy clinicians. Tumor-isolated lymphocytes were also added to the tumoroids, using secondary droplets in proof-of-concept experiments.
These results show the relevance of the methodology for screening large numbers of drugs, a wide range of doses, and multiple drug combinations. This methodology will be used for two purposes: 1) new drug screening from the compound library, using the high throughput potential of the chip; and 2) pre-clinical assay for a two-weeks response for personalized medicine, allowing evaluation of drug combinations to flag an optimized treatment with potential clinical application.
Glioblastoma multiforme (GBM) is known as the most aggressive and prevalent brain tumor with a high mortality rate. It is reported in people who are as young as 10 years old to as old as over 70 years old, exhibiting inter and intra tumor heterogeneity. There are several genomic and proteomic investigations that have been performed to find the unexplored potential targets of the drug against GBM. Therefore, certain effective targets have been taken to further validate the studies embarking on the robustness in the field of medicinal chemistry followed by testing in clinical trials. Also, The Cancer Genome Atlas (TCGA) project has identified certain overexpressed targets involved in the pathogenesis of GBM in three major pathways, i.e., tumor protein 53 (p53), retinoblastoma (RB), and receptor tyrosine kinase (RTK)/rat sarcoma virus (Ras)/phosphoinositide 3-kinase (PI3K) pathways. This review focuses on the compilation of recent developments in the fight against GBM thus, directing future research into the elucidation of pathogenesis and potential cure for GBM. Also, it highlights the potential biomarkers that have undergone extensive research and have promising prognostic and predictive values. Additionally, this manuscript analyses the advent of gene therapy and immunotherapy, unlocking the way to consider treatment approaches other than, or in addition to, conventional chemo-radiation therapies. This review study encompasses all the relevant research studies associated with the pathophysiology, occurrence, diagnostic tools, and therapeutic intervention for GBM. It highlights the evolution of various therapeutic perspectives against GBM from the most conventional form of radiotherapy to the recent advancement of gene/cell/immune therapy. Further, the review focuses on various targeted therapies for GBM including chemotherapy sensitization, radiotherapy, nanoparticles based, immunotherapy, cell therapy, and gene therapy which would offer a comprehensive account for exploring several facets related to GBM prognostics.
[Names] => Manisha Singh ... Rachana [Doi] => 10.37349/etat.2022.00118 [Published] => December 30, 2022 [Viewed] => 1262 [Downloaded] => 51 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2022.00118 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 70 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2022;3:866–888 [Recommend] => 0 [Keywords] => P53 pathway, retinoblastoma pathway, receptor tyrosine kinase (RTK)/rat sarcoma virus (Ras)/phosphoinositide 3-kinase (PI3K) pathway, theranostic biomarkers, immune therapy, gene therapy [DetailTitle] => Cancer Immunotherapy and Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/70 [Id] => 1002118 [ris] => https://www.explorationpub.com/uploads/Article/A1002118/a8914ecb673bf36ba6f394b87fe5b82a.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002118/3ccc46e5d66133912c626c8dbb07e724.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Singh M, Jindal D, Agarwal V, Pathak D, Sharma M, Pancham P, et al. New phase therapeutic pursuits for targeted drug delivery in glioblastoma multiforme. Explor Target Antitumor Ther. 2022;3:866–88. https://doi.org/10.37349/etat.2022.00118 [Jindex] => 0 [CName] => ManishaSingh, [CEmail] => manishasingh1295@gmail.com, [Ris_Time] => 2022-12-30 05:35:36 [Bib_Time] => 2022-12-28 06:38:08 [KeysWordContens] => New phase therapeutic pursuits for targeted drug delivery in glioblastoma multiforme, P53 pathway, retinoblastoma pathway, receptor tyrosine kinase (RTK)/rat sarcoma virus (Ras)/phosphoinositide 3-kinase (PI3K) pathway, theranostic biomarkers, immune therapy, gene therapy, Glioblastoma multiforme (GBM) is known as the most aggressive and prevalent brain tumor with a high mortality rate. It is reported in people who are as young as 10 years old to as old as over 70 years old, exhibiting inter and intra tumor heterogeneity. There are several genomic and proteomic investigations that have been performed to find the unexplored potential targets of the drug against GBM. Therefore, certain effective targets have been taken to further validate the studies embarking on the robustness in the field of medicinal chemistry followed by testing in clinical trials. Also, The Cancer Genome Atlas (TCGA) project has identified certain overexpressed targets involved in the pathogenesis of GBM in three major pathways, i.e., tumor protein 53 (p53), retinoblastoma (RB), and receptor tyrosine kinase (RTK)/rat sarcoma virus (Ras)/phosphoinositide 3-kinase (PI3K) pathways. This review focuses on the compilation of recent developments in the fight against GBM thus, directing future research into the elucidation of pathogenesis and potential cure for GBM. Also, it highlights the potential biomarkers that have undergone extensive research and have promising prognostic and predictive values. Additionally, this manuscript analyses the advent of gene therapy and immunotherapy, unlocking the way to consider treatment approaches other than, or in addition to, conventional chemo-radiation therapies. This review study encompasses all the relevant research studies associated with the pathophysiology, occurrence, diagnostic tools, and therapeutic intervention for GBM. It highlights the evolution of various therapeutic perspectives against GBM from the most conventional form of radiotherapy to the recent advancement of gene/cell/immune therapy. Further, the review focuses on various targeted therapies for GBM including chemotherapy sensitization, radiotherapy, nanoparticles based, immunotherapy, cell therapy, and gene therapy which would offer a comprehensive account for exploring several facets related to GBM prognostics. ,Manisha Singh ... Rachana [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 1 ) [119] => Array ( [ArticleId] => 468 [Create_Time] => 2023-02-07 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230614071730.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002119/1002119.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002119/1002119.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002119/1002119_cover.png [JournalsId] => 4 [Title] => Artificial intelligence fusion for predicting survival of rectal cancer patients using immunohistochemical expression of Ras homolog family member B in biopsy [Abstract] => Aim: The process of biomarker discovery is being accelerated with the application of artificial intelligence (AI), including machine learning. Biomarkers of diseases are useful because they are i [AbstractComplete] =>The process of biomarker discovery is being accelerated with the application of artificial intelligence (AI), including machine learning. Biomarkers of diseases are useful because they are indicators of pathogenesis or measures of responses to therapeutic treatments, and therefore, play a key role in new drug development. Proteins are among the candidates for biomarkers of rectal cancer, which need to be explored using state-of-the-art AI to be utilized for prediction, prognosis, and therapeutic treatment. This paper aims to investigate the predictive power of Ras homolog family member B (RhoB) protein in rectal cancer.
This study introduces the integration of pretrained convolutional neural networks and support vector machines (SVMs) for classifying biopsy samples of immunohistochemical expression of protein RhoB in rectal-cancer patients to validate its biologic measure in biopsy. Features of the immunohistochemical expression images were extracted by the pretrained networks and used for binary classification by the SVMs into two groups of less and more than 5-year survival rates.
The fusion of neural search architecture network (NASNet)-Large for deep-layer feature extraction and classifier using SVMs provided the best average classification performance with a total accuracy = 85%, prediction of survival rate of more than 5 years = 90%, and prediction of survival rate of less than 5 years = 75%.
The finding obtained from the use of AI reported in this study suggest that RhoB expression on rectal-cancer biopsy can be potentially used as a biomarker for predicting survival outcomes in rectal-cancer patients, which can be informative for clinical decision making if the patient would be recommended for preoperative therapy.
Cancer-associated fibroblasts (CAFs) are a major point of interest in modern oncology. Their interest resides in their ability to favor tumor growth without carrying genetic mutations. From a translational standpoint, they are potential therapeutic targets, particularly for hard-to-treat solid cancers. CAFs can be defined as non-tumor cells within the tumor microenvironment that have the morphological traits of fibroblasts, are negative for lineage-specific markers (e.g., leukocyte, endothelium), and enhance tumor progression in a multi-pronged manner. Two often-mentioned aspects of CAF biology are their ability to alter the mechanics and architecture of the tumor microenvironment, and also to drive local immunosuppression. These two aspects are the specific focus of this work, which also contains a brief summary of novel therapeutic interventions under study to normalize or eliminate CAFs from the tumor microenvironment.
[Names] => Vanessa C. Talayero, Miguel Vicente-Manzanares [Doi] => 10.37349/etat.2023.00120 [Published] => February 20, 2023 [Viewed] => 833 [Downloaded] => 24 [Subject] => Perspective [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.000120 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 70 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:17–27 [Recommend] => 0 [Keywords] => Fibroblast, transforming growth factor-β, immunosuppression, cell mechanics, solid tumors, contractility [DetailTitle] => Cancer Immunotherapy and Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/70 [Id] => 1002120 [ris] => https://www.explorationpub.com/uploads/Article/A1002120/330dca089e11f8769521111ce5e62da1.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002120/22e4ae1aed907a9221574a50fbb3cde3.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Talayero VC, Vicente-Manzanares M. A primer on cancer-associated fibroblast mechanics and immunosuppressive ability. Explor Target Antitumor Ther. 2023;4:17–27. https://doi.org/10.37349/etat.2023.00120 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-02-20 03:52:17 [Bib_Time] => 2023-02-20 03:52:17 [KeysWordContens] => A primer on cancer-associated fibroblast mechanics and immunosuppressive ability, Fibroblast, transforming growth factor-β, immunosuppression, cell mechanics, solid tumors, contractility, Cancer-associated fibroblasts (CAFs) are a major point of interest in modern oncology. Their interest resides in their ability to favor tumor growth without carrying genetic mutations. From a translational standpoint, they are potential therapeutic targets, particularly for hard-to-treat solid cancers. CAFs can be defined as non-tumor cells within the tumor microenvironment that have the morphological traits of fibroblasts, are negative for lineage-specific markers (e.g., leukocyte, endothelium), and enhance tumor progression in a multi-pronged manner. Two often-mentioned aspects of CAF biology are their ability to alter the mechanics and architecture of the tumor microenvironment, and also to drive local immunosuppression. These two aspects are the specific focus of this work, which also contains a brief summary of novel therapeutic interventions under study to normalize or eliminate CAFs from the tumor microenvironment. ,Vanessa C. Talayero, Miguel Vicente-Manzanares [PublishedText] => Published [IsEdit] => 0 [AccountId] => 46 [Zh] => 1 ) [121] => Array ( [ArticleId] => 483 [Create_Time] => 2023-02-25 [zipUrl] => https://www.explorationpub.com/uploads/zip/202302/20230225082914.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002121/1002121.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002121/1002121.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002121/1002121_cover.png [JournalsId] => 4 [Title] => Liquid biopsy and glioblastoma [Abstract] => Glioblastoma is the most common and malignant primary brain tumor. Despite a century of research efforts, the survival of patients has not significantly improved. Currently, diagnosis is based on ne [AbstractComplete] =>Glioblastoma is the most common and malignant primary brain tumor. Despite a century of research efforts, the survival of patients has not significantly improved. Currently, diagnosis is based on neuroimaging techniques followed by histopathological and molecular analysis of resected or biopsied tissue. A recent paradigm shift in diagnostics ranks the molecular analysis of tissue samples as the new gold standard over classical histopathology, thus correlating better with the biological behavior of glioblastoma and clinical prediction, especially when a tumor lacks the typical hallmarks for glioblastoma. Liquid biopsy aims to detect and quantify tumor-derived content, such as nucleic acids (DNA/RNA), circulating tumor cells (CTCs), or extracellular vesicles (EVs) in biofluids, mainly blood, cerebrospinal fluid (CSF), or urine. Liquid biopsy has the potential to overcome the limitations of both neuroimaging and tissue-based methods to identify early recurrence and to differentiate tumor progression from pseudoprogression, without the risks of repeated surgical biopsies. This review highlights the origins and time-frame of liquid biopsy in glioblastoma and points to recent developments, limitations, and challenges of adding liquid biopsy to support the clinical management of glioblastoma patients.
[Names] => Robert H. Eibl, Markus Schneemann [Doi] => 10.37349/etat.2023.00121 [Published] => February 25, 2023 [Viewed] => 1682 [Downloaded] => 38 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00121 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 75 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:28–41 [Recommend] => 0 [Keywords] => Liquid biopsy, glioblastoma, cell-free DNA, circulating tumor DNA, minimal residual disease, monitoring, circulating tumor cells, treatment response [DetailTitle] => Theranostic Frontiers in Neuro-Oncology [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/75 [Id] => 1002121 [ris] => https://www.explorationpub.com/uploads/Article/A1002121/0520a0ab712e8a474cf5c1a33fe08cde.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002121/2bcaade15ad5fee3e52c21b20ad4f75e.bib [ens] => [Cited] => 8 [Cited_Time] => 2024-04-27 [CitethisArticle] => Eibl RH, Schneemann M. Liquid biopsy and glioblastoma. Explor Target Antitumor Ther. 2023;4:28–41. https://doi.org/10.37349//etat.2023.00121 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-02-22 05:49:36 [Bib_Time] => 2023-02-22 05:49:36 [KeysWordContens] => Liquid biopsy and glioblastoma, Liquid biopsy, glioblastoma, cell-free DNA, circulating tumor DNA, minimal residual disease, monitoring, circulating tumor cells, treatment response, Glioblastoma is the most common and malignant primary brain tumor. Despite a century of research efforts, the survival of patients has not significantly improved. Currently, diagnosis is based on neuroimaging techniques followed by histopathological and molecular analysis of resected or biopsied tissue. A recent paradigm shift in diagnostics ranks the molecular analysis of tissue samples as the new gold standard over classical histopathology, thus correlating better with the biological behavior of glioblastoma and clinical prediction, especially when a tumor lacks the typical hallmarks for glioblastoma. Liquid biopsy aims to detect and quantify tumor-derived content, such as nucleic acids (DNA/RNA), circulating tumor cells (CTCs), or extracellular vesicles (EVs) in biofluids, mainly blood, cerebrospinal fluid (CSF), or urine. Liquid biopsy has the potential to overcome the limitations of both neuroimaging and tissue-based methods to identify early recurrence and to differentiate tumor progression from pseudoprogression, without the risks of repeated surgical biopsies. This review highlights the origins and time-frame of liquid biopsy in glioblastoma and points to recent developments, limitations, and challenges of adding liquid biopsy to support the clinical management of glioblastoma patients. ,Robert H. Eibl, Markus Schneemann [PublishedText] => Published [IsEdit] => 0 [AccountId] => 46 [Zh] => 1 ) [122] => Array ( [ArticleId] => 494 [Create_Time] => 2023-02-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202303/20230307082642.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002122/1002122.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002122/1002122.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002122/1002122_cover.png [JournalsId] => 4 [Title] => Enhancement of reactive oxygen species production in triple negative breast cancer cells treated with electric pulses and resveratrol [Abstract] => Aim: Triple negative breast cancer (TNBC) is difficult to treat since it lacks all the three most commonly targeted hormone receptors. Patients afflicted with TNBC are treated with platinum core [AbstractComplete] =>Triple negative breast cancer (TNBC) is difficult to treat since it lacks all the three most commonly targeted hormone receptors. Patients afflicted with TNBC are treated with platinum core chemotherapeutics, such as cisplatin. Despite the initial effective anticancer effects of cisplatin, TNBC attenuates its effect and develops resistance eventually, which results in tumor reoccurrence. Hence, there is a critical demand for effective, alternative, and natural ways to treat TNBC. Towards this, a promising technique for inhibiting TNBC cell proliferation involves promoting the production of reactive oxygen species (ROS), which triggers pro-apoptotic caspases 9 and 3. Resveratrol (RESV), an active bio compound found in naturally available fruits, such as grapes, is utilized in this research for that. In addition, electrochemotherapy (ECT), which involves the application of electrical pulses (EP), was utilized to enhance the uptake of RESV.
MDA-MB-231, human TNBC cells were treated with/out RESV, and eight 600–1,000 V/cm, 100 μs pulses at 1 Hz. The cells were characterized by using various assays, including viability assay, and ROS assay.
A TNBC cell viability of as low as 20% was obtained at 24 h (it was 13% at 60 h), demonstrating the potential of this novel treatment. ROS production was the highest in the combination of EP at 1,000 V/cm along with RESV at 100 μmol/L.
Results indicate that RESV has the potential as an anti-TNBC agent and that EP + RESV can significantly enhance the cell death to reduce MDA-MB-231 cell viability by increasing ROS production and triggering apoptosis.
This study shows how important it is to coordinate research on Ficus deltoidea Jack (FD) so that results from different sources can be compared directly and a scientific conclusion can be made.
The author looked for research papers on Ficus (F.) deltoidea on Google Scholar, Science Direct, Google.com, Wiley, PubMed, Hindawi, Springer, and other related databases. This analysis excludes data that cannot be trusted, thesis papers, and review articles about F. deltoidea.
In traditional medicine, the plant’s leaves and syconia are used to cure a wide variety of ailments, including itchiness, diarrhoea, cancer, sexual dysfunction, age-related issues, malaria, cancer, anxiety, pain, constipation, fever, diabetes, tooth pain, and tooth decay. In vitro and in vivo studies showed the effectiveness of the leaves against cancer cell lines.
Based on the existing research on the health benefits of FD, it is critical to focus on its more active constituents and their identification, determination, further development, and, most importantly, standardization of the leaves for the management and treatment of cancer and its related cases. More research is needed before it can be considered a promising herbal source of novel medication candidates for treating various disorders.
Macrophages, as ubiquitous and functionally diverse immune cells, play a central role in innate immunity and initiate adaptive immunity. Especially, tumor-associated macrophages (TAMs) are crucial contributors to the tumorigenesis and development of cancer. Thus, macrophages are emerging potential targets for cancer treatment. Among the numerous targeted therapeutic options, gene therapy is one of the most potential therapeutic strategies via directly and specifically regulating biological functions of macrophages at the gene level for cancer treatment. This short review briefly introduces the characteristics of macrophage populations, the functions of TAM in the occurrence, and the progress of cancer. It also summarized some representative examples to highlight the current progress in TAM-targeted gene therapy. The review hopes to provide new insights into macrophage-targeted gene therapy for precision cancer therapy.
[Names] => Yuanzheng Huang ... Xiaoxuan Liu [Doi] => 10.37349/etat.2023.00124 [Published] => February 28, 2023 [Viewed] => 1451 [Downloaded] => 43 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00124 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 51 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:89–101 [Recommend] => 0 [Keywords] => Macrophages, gene therapy, cancer [DetailTitle] => Gene Delivery Approach to Fight Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/51 [Id] => 1002124 [ris] => https://www.explorationpub.com/uploads/Article/A1002124/9d4c87d5908c9098e5cdb2a4b370c813.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002124/c015053c8afbfe0a1ad11c8a7d58f502.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-27 [CitethisArticle] => Huang YZ, Wang ZH, Gong JN, Zhu DD, Chen W, Li FZ, et al. Macrophages as potential targets in gene therapy for cancer treatment. Explor Target Antitumor Ther. 2023;4:89–101. https://doi.org/10.37349/etat.2023.00124 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-02-28 03:39:05 [Bib_Time] => 2023-02-28 03:39:05 [KeysWordContens] => Macrophages as potential targets in gene therapy for cancer treatment, Macrophages, gene therapy, cancer, Macrophages, as ubiquitous and functionally diverse immune cells, play a central role in innate immunity and initiate adaptive immunity. Especially, tumor-associated macrophages (TAMs) are crucial contributors to the tumorigenesis and development of cancer. Thus, macrophages are emerging potential targets for cancer treatment. Among the numerous targeted therapeutic options, gene therapy is one of the most potential therapeutic strategies via directly and specifically regulating biological functions of macrophages at the gene level for cancer treatment. This short review briefly introduces the characteristics of macrophage populations, the functions of TAM in the occurrence, and the progress of cancer. It also summarized some representative examples to highlight the current progress in TAM-targeted gene therapy. The review hopes to provide new insights into macrophage-targeted gene therapy for precision cancer therapy. ,Yuanzheng Huang ... Xiaoxuan Liu [PublishedText] => Published [IsEdit] => 0 [AccountId] => 57 [Zh] => 1 ) [125] => Array ( [ArticleId] => 506 [Create_Time] => 2023-03-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202303/20230301030629.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002125/1002125.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002125/1002125.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002125/1002125_cover.png [JournalsId] => 4 [Title] => Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer [Abstract] => Liquid biopsy is a diagnostic repeatable test, which in last years has emerged as a powerful tool for profiling cancer genomes in real-time with minimal invasiveness and tailoring oncological decisi [AbstractComplete] =>Liquid biopsy is a diagnostic repeatable test, which in last years has emerged as a powerful tool for profiling cancer genomes in real-time with minimal invasiveness and tailoring oncological decision-making. It analyzes different blood-circulating biomarkers and circulating tumor DNA (ctDNA) is the preferred one. Nevertheless, tissue biopsy remains the gold standard for molecular evaluation of solid tumors whereas liquid biopsy is a complementary tool in many different clinical settings, such as treatment selection, monitoring treatment response, cancer clonal evolution, prognostic evaluation, as well as the detection of early disease and minimal residual disease (MRD). A wide number of technologies have been developed with the aim of increasing their sensitivity and specificity with acceptable costs. Moreover, several preclinical and clinical studies have been conducted to better understand liquid biopsy clinical utility. Anyway, several issues are still a limitation of its use such as false positive and negative results, results interpretation, and standardization of the panel tests. Although there has been rapid development of the research in these fields and recent advances in the clinical setting, many clinical trials and studies are still needed to make liquid biopsy an instrument of clinical routine. This review provides an overview of the current and future clinical applications and opening questions of liquid biopsy in different oncological settings, with particular attention to ctDNA liquid biopsy.
[Names] => Vincenza Caputo ... Stefania Napolitano [Doi] => 10.37349/etat.2023.00125 [Published] => February 28, 2023 [Viewed] => 1844 [Downloaded] => 61 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00125 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 61 [TitleAbbr] => Explor Target Antitumor Ther [Pages] => 2023;4:102–138 [Recommend] => 0 [Keywords] => Liquid biopsy, circulating tumor DNA, precision medicine, clinical trials, minimal residual disease [DetailTitle] => The Implementation of Liquid Biopsy in Clinical Practice for Different Solid Tumor [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/61 [Id] => 1002125 [ris] => https://www.explorationpub.com/uploads/Article/A1002125/640b4b8d16a5066d69bfe9b6257d127d.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002125/68f36cb692f238845b538cf76c993108.bib [ens] => [Cited] => 17 [Cited_Time] => 2024-04-27 [CitethisArticle] => Caputo V, Ciardiello F, Della Corte CM, Martini G, Troiani T, Napolitano S. Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer. Explor Target Antitumor Ther. 2023;4:102–38. https://doi.org/10.37349/etat.2023.00125 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-02-27 01:44:37 [Bib_Time] => 2023-02-27 01:43:22 [KeysWordContens] => Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer, Liquid biopsy, circulating tumor DNA, precision medicine, clinical trials, minimal residual disease, Liquid biopsy is a diagnostic repeatable test, which in last years has emerged as a powerful tool for profiling cancer genomes in real-time with minimal invasiveness and tailoring oncological decision-making. It analyzes different blood-circulating biomarkers and circulating tumor DNA (ctDNA) is the preferred one. Nevertheless, tissue biopsy remains the gold standard for molecular evaluation of solid tumors whereas liquid biopsy is a complementary tool in many different clinical settings, such as treatment selection, monitoring treatment response, cancer clonal evolution, prognostic evaluation, as well as the detection of early disease and minimal residual disease (MRD). A wide number of technologies have been developed with the aim of increasing their sensitivity and specificity with acceptable costs. Moreover, several preclinical and clinical studies have been conducted to better understand liquid biopsy clinical utility. Anyway, several issues are still a limitation of its use such as false positive and negative results, results interpretation, and standardization of the panel tests. Although there has been rapid development of the research in these fields and recent advances in the clinical setting, many clinical trials and studies are still needed to make liquid biopsy an instrument of clinical routine. This review provides an overview of the current and future clinical applications and opening questions of liquid biopsy in different oncological settings, with particular attention to ctDNA liquid biopsy. ,Vincenza Caputo ... Stefania Napolitano [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 1 ) [126] => Array ( [ArticleId] => 510 [Create_Time] => 2023-03-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202303/20230301035440.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002126/1002126.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002126/1002126.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002126/1002126_cover.png [JournalsId] => 4 [Title] => Research progress in molecular pathology markers in medulloblastoma [Abstract] => Glioblastoma is the most common and malignant primary brain tumor. Despite a century of research efforts, the survival of patients has not significantly improved. Currently, diagnosis is based on ne [AbstractComplete] =>Medulloblastoma (MB) is the commonest primary malignant brain cancer. The current treatment of MB is usually surgical resection combined with radiotherapy or chemotherapy. Although great progress has been made in the clinical management of MB, tumor metastasis and recurrence are still the main cause of death. Therefore, definitive and timely diagnosis is of great importance for improving therapeutic effects on MB. In 2016, the World Health Organization (WHO) divided MB into four subtypes: wingless-type mouse mammary tumor virus integration site (WNT), sonic hedgehog (SHH), non-WNT/non-SHH group 3, and group 4. Each subtype of MB has a unique profile in copy number variation, DNA alteration, gene transcription, or post-transcriptional/translational modification, all of which are associated with different biological manifestations, clinical features, and prognosis. This article reviewed the research progress of different molecular pathology markers in MB and summarized some targeted drugs against these molecular markers, hoping to stimulate the clinical application of these molecular markers in the classification, diagnosis, and treatment of MB.
[Names] => Zixuan Zhou ... Shangfeng Gao [Doi] => 10.37349/etat.2023.00126 [Published] => February 28, 2023 [Viewed] => 1003 [Downloaded] => 26 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00126 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 75 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:139–156 [Recommend] => 0 [Keywords] => Medulloblastoma, molecular pathology, children, diagnosis, targeted therapy [DetailTitle] => Theranostic Frontiers in Neuro-Oncology [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/75 [Id] => 1002126 [ris] => https://www.explorationpub.com/uploads/Article/A1002126/2dbeacfec1133193f2452799d475d75b.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002126/b8c0f0e7202d05aae457d5b461ea7786.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Zhou Z, Zhu B, Meng Q, Zhang T, Wu Y, Yu R, et al. Research progress in molecular pathology markers in medulloblastoma. Explor Target Antitumor Ther. 2023;4:139–56. https://doi.org/10.37349/etat.2023.00126 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-02-27 07:16:20 [Bib_Time] => 2023-02-27 05:46:35 [KeysWordContens] => Research progress in molecular pathology markers in medulloblastoma, Medulloblastoma, molecular pathology, children, diagnosis, targeted therapy, Medulloblastoma (MB) is the commonest primary malignant brain cancer. The current treatment of MB is usually surgical resection combined with radiotherapy or chemotherapy. Although great progress has been made in the clinical management of MB, tumor metastasis and recurrence are still the main cause of death. Therefore, definitive and timely diagnosis is of great importance for improving therapeutic effects on MB. In 2016, the World Health Organization (WHO) divided MB into four subtypes: wingless-type mouse mammary tumor virus integration site (WNT), sonic hedgehog (SHH), non-WNT/non-SHH group 3, and group 4. Each subtype of MB has a unique profile in copy number variation, DNA alteration, gene transcription, or post-transcriptional/translational modification, all of which are associated with different biological manifestations, clinical features, and prognosis. This article reviewed the research progress of different molecular pathology markers in MB and summarized some targeted drugs against these molecular markers, hoping to stimulate the clinical application of these molecular markers in the classification, diagnosis, and treatment of MB. ,Zixuan Zhou ... Shangfeng Gao [PublishedText] => Published [IsEdit] => 0 [AccountId] => 46 [Zh] => 1 ) [127] => Array ( [ArticleId] => 514 [Create_Time] => 2023-03-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202302/20230228102822.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002127/1002127.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002127/1002127.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002127/1002127_cover.png [JournalsId] => 4 [Title] => Artificial intelligence applications in pediatric oncology diagnosis [Abstract] => Artificial intelligence (AI) algorithms have been applied in abundant medical tasks with high accuracy and efficiency. Physicians can improve their diagnostic efficiency with the assistance of AI techniques for improving the subsequent personalized treatment and surveillance. AI algorithms fundamentally capture data, identify underlying patterns, achieve preset endpoints, and provide decisions and predictions about real-world events with working principles of machine learning and deep learning. AI algorithms with sufficient graphic processing unit power have been demonstrated to provide timely diagnostic references based on preliminary training of large amounts of clinical and imaging data. The sample size issue is an inevitable challenge for pediatric oncology considering its low morbidity and individual heterogeneity. However, this problem may be solved in the near future considering the exponential advancements of AI algorithms technically to decrease the dependence of AI operation on the amount of data sets and the efficiency of computing power. For instance, it could be a feasible solution by shifting convolutional neural networks (CNNs) from adults and sharing CNN algorithms across multiple institutions besides original data. The present review provides important insights into emerging AI applications for the diagnosis of pediatric oncology by systematically overviewing of up-to-date literature. [AbstractComplete] =>Artificial intelligence (AI) algorithms have been applied in abundant medical tasks with high accuracy and efficiency. Physicians can improve their diagnostic efficiency with the assistance of AI techniques for improving the subsequent personalized treatment and surveillance. AI algorithms fundamentally capture data, identify underlying patterns, achieve preset endpoints, and provide decisions and predictions about real-world events with working principles of machine learning and deep learning. AI algorithms with sufficient graphic processing unit power have been demonstrated to provide timely diagnostic references based on preliminary training of large amounts of clinical and imaging data. The sample size issue is an inevitable challenge for pediatric oncology considering its low morbidity and individual heterogeneity. However, this problem may be solved in the near future considering the exponential advancements of AI algorithms technically to decrease the dependence of AI operation on the amount of data sets and the efficiency of computing power. For instance, it could be a feasible solution by shifting convolutional neural networks (CNNs) from adults and sharing CNN algorithms across multiple institutions besides original data. The present review provides important insights into emerging AI applications for the diagnosis of pediatric oncology by systematically overviewing of up-to-date literature.
[Names] => Yuhan Yang ... Yuan Li [Doi] => 10.37349/etat.2023.00127 [Published] => February 28, 2023 [Viewed] => 1079 [Downloaded] => 29 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00127 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 88 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:157–169 [Recommend] => 0 [Keywords] => Pediatric oncology, artificial intelligence, cancer diagnosis, machine learning, deep learning [DetailTitle] => Artificial Intelligence for Precision Oncology [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/88 [Id] => 1002127 [ris] => https://www.explorationpub.com/uploads/Article/A1002127/2609aa0c789b59eaf94ac3367ee26e37.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002127/d6ed3dba74c04c847c7a332fa545477c.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Yang Y, Zhang Y, Li Y. Artificial intelligence applications in pediatric oncology diagnosis. Explor Target Antitumor Ther. 2023;4:157–69. https://doi.org/10.37349/etat.2023.00127 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-02-27 10:20:01 [Bib_Time] => 2023-02-27 10:20:01 [KeysWordContens] => Artificial intelligence applications in pediatric oncology diagnosis, Pediatric oncology, artificial intelligence, cancer diagnosis, machine learning, deep learning, Artificial intelligence (AI) algorithms have been applied in abundant medical tasks with high accuracy and efficiency. Physicians can improve their diagnostic efficiency with the assistance of AI techniques for improving the subsequent personalized treatment and surveillance. AI algorithms fundamentally capture data, identify underlying patterns, achieve preset endpoints, and provide decisions and predictions about real-world events with working principles of machine learning and deep learning. AI algorithms with sufficient graphic processing unit power have been demonstrated to provide timely diagnostic references based on preliminary training of large amounts of clinical and imaging data. The sample size issue is an inevitable challenge for pediatric oncology considering its low morbidity and individual heterogeneity. However, this problem may be solved in the near future considering the exponential advancements of AI algorithms technically to decrease the dependence of AI operation on the amount of data sets and the efficiency of computing power. For instance, it could be a feasible solution by shifting convolutional neural networks (CNNs) from adults and sharing CNN algorithms across multiple institutions besides original data. The present review provides important insights into emerging AI applications for the diagnosis of pediatric oncology by systematically overviewing of up-to-date literature. ,Yuhan Yang ... Yuan Li [PublishedText] => Published [IsEdit] => 0 [AccountId] => 47 [Zh] => 1 ) [128] => Array ( [ArticleId] => 539 [Create_Time] => 2023-04-21 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230612085446.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002128/1002128.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002128/1002128.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002128/1002128_cover.png [JournalsId] => 4 [Title] => Cancer resistance via the downregulation of the tumor suppressors RKIP and PTEN expressions: therapeutic implications [Abstract] => The Raf kinase inhibitor protein (RKIP) has been reported to be underexpressed in many cancers and plays a role in the regulation of tumor cells' survival, proliferation, invasion, and me [AbstractComplete] =>The Raf kinase inhibitor protein (RKIP) has been reported to be underexpressed in many cancers and plays a role in the regulation of tumor cells' survival, proliferation, invasion, and metastasis, hence, a tumor suppressor. RKIP also regulates tumor cell resistance to cytotoxic drugs/cells. Likewise, the tumor suppressor, phosphatase and tensin homolog (PTEN), which inhibits the phosphatidylinositol 3 kinase (PI3K)/AKT pathway, is either mutated, underexpressed, or deleted in many cancers and shares with RKIP its anti-tumor properties and its regulation in resistance. The transcriptional and posttranscriptional regulations of RKIP and PTEN expressions and their roles in resistance were reviewed. The underlying mechanism of the interrelationship between the signaling expressions of RKIP and PTEN in cancer is not clear. Several pathways are regulated by RKIP and PTEN and the transcriptional and post-transcriptional regulations of RKIP and PTEN is significantly altered in cancers. In addition, RKIP and PTEN play a key role in the regulation of tumor cells response to chemotherapy and immunotherapy. In addition, molecular and bioinformatic data revealed crosstalk signaling networks that regulate the expressions of both RKIP and PTEN. These crosstalks involved the mitogen-activated protein kinase (MAPK)/PI3K pathways and the dysregulated nuclear factor-kappaB (NF-κB)/Snail/Yin Yang 1 (YY1)/RKIP/PTEN loop in many cancers. Furthermore, further bioinformatic analyses were performed to investigate the correlations (positive or negative) and the prognostic significance of the expressions of RKIP or PTEN in 31 different human cancers. These analyses were not uniform and only revealed that there was a positive correlation between the expression of RKIP and PTEN only in few cancers. These findings demonstrated the existence of signaling cross-talks between RKIP and PTEN and both regulate resistance. Targeting either RKIP or PTEN (alone or in combination with other therapies) may be sufficient to therapeutically inhibit tumor growth and reverse the tumor resistance to cytotoxic therapies.
[Names] => Matthew Moghaddam ... Benjamin Bonavida [Doi] => 10.37349/etat.2023.00128 [Published] => April 20, 2023 [Viewed] => 1005 [Downloaded] => 29 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00128 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 70 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:170–207 [Recommend] => 0 [Keywords] => RKIP, PTEN, cross-talks, signaling, bioinformatics, resistance [DetailTitle] => Cancer Immunotherapy and Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/70 [Id] => 1002128 [ris] => https://www.explorationpub.com/uploads/Article/A1002128/09f14508a7357a6937c1faec38ae4115.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002128/c941541d9a260e615f45d97cb304c00e.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Moghaddam M, Vivarelli S, Falzone L, Libra M, Bonavida B. Cancer resistance via the downregulation of the tumor suppressors RKIP and PTEN expressions: therapeutic implications. Explor Target Antitumor Ther. 2023;4:170–207. https://doi.org/10.37349/etat.2023.00128 [Jindex] => 0 [CName] => BenjaminBonavida, [CEmail] => bbonavida@mednet.ucla.edu, [Ris_Time] => 2023-04-17 01:44:36 [Bib_Time] => 2023-04-19 00:46:35 [KeysWordContens] => Cancer resistance via the downregulation of the tumor suppressors RKIP and PTEN expressions: therapeutic implications, RKIP, PTEN, cross-talks, signaling, bioinformatics, resistance, The Raf kinase inhibitor protein (RKIP) has been reported to be underexpressed in many cancers and plays a role in the regulation of tumor cells' survival, proliferation, invasion, and metastasis, hence, a tumor suppressor. RKIP also regulates tumor cell resistance to cytotoxic drugs/cells. Likewise, the tumor suppressor, phosphatase and tensin homolog (PTEN), which inhibits the phosphatidylinositol 3 kinase (PI3K)/AKT pathway, is either mutated, underexpressed, or deleted in many cancers and shares with RKIP its anti-tumor properties and its regulation in resistance. The transcriptional and posttranscriptional regulations of RKIP and PTEN expressions and their roles in resistance were reviewed. The underlying mechanism of the interrelationship between the signaling expressions of RKIP and PTEN in cancer is not clear. Several pathways are regulated by RKIP and PTEN and the transcriptional and post-transcriptional regulations of RKIP and PTEN is significantly altered in cancers. In addition, RKIP and PTEN play a key role in the regulation of tumor cells response to chemotherapy and immunotherapy. In addition, molecular and bioinformatic data revealed crosstalk signaling networks that regulate the expressions of both RKIP and PTEN. These crosstalks involved the mitogen-activated protein kinase (MAPK)/PI3K pathways and the dysregulated nuclear factor-kappaB (NF-κB)/Snail/Yin Yang 1 (YY1)/RKIP/PTEN loop in many cancers. Furthermore, further bioinformatic analyses were performed to investigate the correlations (positive or negative) and the prognostic significance of the expressions of RKIP or PTEN in 31 different human cancers. These analyses were not uniform and only revealed that there was a positive correlation between the expression of RKIP and PTEN only in few cancers. These findings demonstrated the existence of signaling cross-talks between RKIP and PTEN and both regulate resistance. Targeting either RKIP or PTEN (alone or in combination with other therapies) may be sufficient to therapeutically inhibit tumor growth and reverse the tumor resistance to cytotoxic therapies. ,Matthew Moghaddam ... Benjamin Bonavida [PublishedText] => Published [IsEdit] => 0 [AccountId] => 57 [Zh] => 1 ) [129] => Array ( [ArticleId] => 542 [Create_Time] => 2023-04-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202304/20230425072723.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002130/1002130.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002130/1002130.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002130/1002130_cover.png [JournalsId] => 4 [Title] => Clinicopathological relevance of stem cell marker growth and differentiation factor 3 in esophageal squamous cell carcinoma [Abstract] => Esophageal squamous cell carcinoma (ESCC) is the second leading cause of cancer-related deaths in Iran, often diagnosed in advanced stages with a poor prognosis. Growth and differentiation factor 3 [AbstractComplete] =>Esophageal squamous cell carcinoma (ESCC) is the second leading cause of cancer-related deaths in Iran, often diagnosed in advanced stages with a poor prognosis. Growth and differentiation factor 3 (GDF3) is a member of the transforming growth factor-beta (TGF-β) superfamily. It acts as an inhibitor of bone morphogenetic proteins (BMPs) signaling pathway associated with pluripotent embryonic and cancer stem cells (CSCs) characteristics. Since its expression in ESCC has not yet been evaluated, the clinicopathological relevance of GDF3 expression was elucidated in ESCC patients. Expression of GDF3 in tumor tissues from 40 ESCC patients was compared to the related margin normal tissues by relatively comparative real-time polymerase chain reaction (PCR). Glyceraldehydes 3-phosphate dehydrogenase (GAPDH) was used as the endogenous control. Likewise, the function of GDF3 in the differentiation and development of embryonic stem cells (ESCs) was also reviewed. GDF3 was significantly overexpressed in 17.5% of tumors and a significant correlation between GDF3 expression and the depth of tumor invasion was observed (P = 0.032). The results suggest that GDF3 expression is likely to have substantial roles in the progression and invasiveness behavior of ESCC. Having considered the importance of CSC markers identification and their exploitation in targeted cancer therapy, GDF3 may be introduced as a promising therapeutic target to inhibit the invasion of tumor cells in ESCC.
[Names] => Sara Tahbazzadeh Moghaddam, Mohammad Mahdi Forghanifard [Doi] => 10.37349/etat.2023.00130 [Published] => April 24, 2023 [Viewed] => 613 [Downloaded] => 16 [Subject] => Letter to the Editor [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00130 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:217–226 [Recommend] => 0 [Keywords] => Cancer stem cell marker, esophageal squamous cell carcinoma, growth and differentiation factor 3, real-time polymerase chain reaction, expressional analysis [DetailTitle] => [DetailUrl] => [Id] => 1002130 [ris] => https://www.explorationpub.com/uploads/Article/A1002130/973634b52d06bc489375c5b8e32ac885.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002130/003fd42d209c9977375ee4513938072a.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Tahbazzadeh Moghaddam S, Forghanifard MM. Clinicopathological relevance of stem cell marker growth and differentiation factor 3 in esophageal squamous cell carcinoma. Explor Target Antitumor Ther. 2023;4:217–26. https://doi.org/10.37349/etat.2023.00130 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-04-18 08:57:38 [Bib_Time] => 2023-04-18 08:57:38 [KeysWordContens] => Clinicopathological relevance of stem cell marker growth and differentiation factor 3 in esophageal squamous cell carcinoma, Cancer stem cell marker, esophageal squamous cell carcinoma, growth and differentiation factor 3, real-time polymerase chain reaction, expressional analysis, Esophageal squamous cell carcinoma (ESCC) is the second leading cause of cancer-related deaths in Iran, often diagnosed in advanced stages with a poor prognosis. Growth and differentiation factor 3 (GDF3) is a member of the transforming growth factor-beta (TGF-β) superfamily. It acts as an inhibitor of bone morphogenetic proteins (BMPs) signaling pathway associated with pluripotent embryonic and cancer stem cells (CSCs) characteristics. Since its expression in ESCC has not yet been evaluated, the clinicopathological relevance of GDF3 expression was elucidated in ESCC patients. Expression of GDF3 in tumor tissues from 40 ESCC patients was compared to the related margin normal tissues by relatively comparative real-time polymerase chain reaction (PCR). Glyceraldehydes 3-phosphate dehydrogenase (GAPDH) was used as the endogenous control. Likewise, the function of GDF3 in the differentiation and development of embryonic stem cells (ESCs) was also reviewed. GDF3 was significantly overexpressed in 17.5% of tumors and a significant correlation between GDF3 expression and the depth of tumor invasion was observed (P = 0.032). The results suggest that GDF3 expression is likely to have substantial roles in the progression and invasiveness behavior of ESCC. Having considered the importance of CSC markers identification and their exploitation in targeted cancer therapy, GDF3 may be introduced as a promising therapeutic target to inhibit the invasion of tumor cells in ESCC. ,Sara Tahbazzadeh Moghaddam, Mohammad Mahdi Forghanifard [PublishedText] => Published [IsEdit] => 0 [AccountId] => 45 [Zh] => 1 ) [130] => Array ( [ArticleId] => 541 [Create_Time] => 2023-04-21 [zipUrl] => https://www.explorationpub.com/uploads/zip/202304/20230421082441.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002129/1002129.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002129/1002129.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002129/1002129_cover.png [JournalsId] => 4 [Title] => Ginnalin A and hamamelitannin: the unique gallotannins with promising anti-carcinogenic potential [Abstract] => Tannins are secondary metabolites that belong to the family of polyphenolic compounds and have gained a huge interest among researchers due to their versatile therapeutic potential. After lignin, th [AbstractComplete] =>Tannins are secondary metabolites that belong to the family of polyphenolic compounds and have gained a huge interest among researchers due to their versatile therapeutic potential. After lignin, these are the second most abundant polyphenols found in almost every plant part like stem, bark, fruit, seed, leaves, etc. Depending upon their structural composition, these polyphenols can be divided into two distinct groups, namely condensed tannins and hydrolysable tannins. Hydrolysable tannins can be further divided into two types: gallotannins and ellagitannins. Gallotannins are formed by the esterification of D-glucose hydroxyl groups with gallic acid. The gallolyl moieties are bound by a depside bond. The current review focuses mainly on the anti-carcinogenic potential of recently discovered gallotannins, ginnalin A, and hamamelitannin (HAM). Both of these gallotannins possess two galloyl moieties linked to a core monosaccharide having anti-oxidant, anti-inflammatory, and anti-carcinogenic abilities. Ginnalin A is found in plants of the genus Acer whereas HAM is present in witch hazel plants. The biosynthetic pathway of ginnalin A along with the mechanism of the anti-cancer therapeutic potential of ginnalin A and HAM has been discussed. This review will certainly help researchers to work further on the chemo-therapeutic abilities of these two unique gallotannins.
[Names] => Rippin ... Anil K. Sharma [Doi] => 10.37349/etat.2023.00129 [Published] => April 21, 2023 [Viewed] => 836 [Downloaded] => 21 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00129 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 73 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:208–216 [Recommend] => 0 [Keywords] => Tannins, gallotannins, ginnalin A, acertannin, anti-carcinogen, hamamelitannin [DetailTitle] => Plant Extracts as an Infinite Resource for New Anticancer Agents [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/73 [Id] => 1002129 [ris] => https://www.explorationpub.com/uploads/Article/A1002129/d798805f03d8374ece9989fb2156f3a7.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002129/2c3db566b01a5989eaa586be2f709a7d.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-27 [CitethisArticle] => Rippin, Beniwal V, Sharma A, Singh BJ, Ramniwas S, Sak K, et al. Ginnalin A and hamamelitannin: the unique gallotannins with promising anti-carcinogenic potential. Explor Target Antitumor Ther. 2023;4:208–16. https://doi.org/10.37349/etat.2023.00129 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-04-18 08:55:06 [Bib_Time] => 2023-04-18 08:55:06 [KeysWordContens] => Ginnalin A and hamamelitannin: the unique gallotannins with promising anti-carcinogenic potential, Tannins, gallotannins, ginnalin A, acertannin, anti-carcinogen, hamamelitannin, Tannins are secondary metabolites that belong to the family of polyphenolic compounds and have gained a huge interest among researchers due to their versatile therapeutic potential. After lignin, these are the second most abundant polyphenols found in almost every plant part like stem, bark, fruit, seed, leaves, etc. Depending upon their structural composition, these polyphenols can be divided into two distinct groups, namely condensed tannins and hydrolysable tannins. Hydrolysable tannins can be further divided into two types: gallotannins and ellagitannins. Gallotannins are formed by the esterification of D-glucose hydroxyl groups with gallic acid. The gallolyl moieties are bound by a depside bond. The current review focuses mainly on the anti-carcinogenic potential of recently discovered gallotannins, ginnalin A, and hamamelitannin (HAM). Both of these gallotannins possess two galloyl moieties linked to a core monosaccharide having anti-oxidant, anti-inflammatory, and anti-carcinogenic abilities. Ginnalin A is found in plants of the genus Acer whereas HAM is present in witch hazel plants. The biosynthetic pathway of ginnalin A along with the mechanism of the anti-cancer therapeutic potential of ginnalin A and HAM has been discussed. This review will certainly help researchers to work further on the chemo-therapeutic abilities of these two unique gallotannins. , Rippin ... Anil K. Sharma [PublishedText] => Published [IsEdit] => 0 [AccountId] => 45 [Zh] => 1 ) [131] => Array ( [ArticleId] => 543 [Create_Time] => 2023-04-25 [zipUrl] => https://www.explorationpub.com/uploads/zip/202304/20230428012738.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002131/1002131.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002131/1002131.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002131/1002131_Cover.png [JournalsId] => 4 [Title] => A potent bioactive fraction against colon cancer from Plectranthus vettiveroides [Abstract] => Aim: This study was designed to investigate the anticancer efficacy of the organic leaf extracts of the plant, Plectranthus vettiveroides (P. vettiveroides), and to analyze the molecular mechanism [AbstractComplete] =>This study was designed to investigate the anticancer efficacy of the organic leaf extracts of the plant, Plectranthus vettiveroides (P. vettiveroides), and to analyze the molecular mechanism of the anticancer activity.
The leaf extracts were prepared by polarity-graded serial extraction of the dried leaf powder. The cytotoxic effect of the extracts was analyzed by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The most active ethyl acetate extract was subjected to bioactivity-guided fractionation by column chromatography, which yielded a cytotoxic fraction designated as the P. vettiveroides fraction (PVF). The anticancer property of PVF was confirmed further by clonogenic assay. The mechanism of PVF-induced cell death was analyzed by flow cytometry and fluorescence microscopy. Additionally, the effects of PVF on apoptotic and cell survival pathways were analyzed using western immunoblot analysis.
A bioactive fraction PVF, was isolated from the ethyl acetate leaf extract. PVF showed significant anticancer activity against colon cancer cells, whilst normal cells were comparatively less affected. PVF induced strong apoptotic stimuli in colorectal carcinoma cell line HCT116, involving both extrinsic and intrinsic pathways. Investigation into the molecular mechanism of anticancer activity of PVF in HCT116 cells revealed that the fraction activates the pro-apoptotic pathway via tumor suppressor protein 53 (p53) and inhibits the anti-apoptotic pathway by regulating phosphatidylinositol 3-kinase (PI3K) signaling.
The findings of this study demonstrate, with mechanism-based evidence, the chemotherapeutic potential of a bioactive fraction PVF, derived from the leaves of the medicinal plant P. vettiveroides against colon cancer.
Neuroendocrine tumours (NETs) are a rare type of tumours that arise from the neuroendocrine cells which are distributed throughout the body. Of all the gastrointestinal tumours only 1–2% account for NETs. They have an extremely low incidence of 0.17% arising in the intrahepatic bile duct epithelium. Majority of hepatic NETs occur as a result of metastases from the primary NETs. Most cases of primary hepatic NET (PHNET) present as a solid nodular mass. However, predominantly cystic PHNET is extremely rare which mimics other cystic space-occupying lesions clinically and radiologically as seen in this case.
[Names] => Mangesh Londhe ... Charusheela Gore [Doi] => 10.37349/etat.2023.00133 [Published] => April 26, 2023 [Viewed] => 617 [Downloaded] => 13 [Subject] => Case Report [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00133 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 41 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:266–272 [Recommend] => 0 [Keywords] => Biliary, cystadenoma, primary neoplasm, synaptophysin [DetailTitle] => Precision Medicine for Cholangiocarcinoma [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/41 [Id] => 1002133 [ris] => https://www.explorationpub.com/uploads/Article/A1002133/ced26e6cc48da5b0684816b760b14f73.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002133/e591cf542c1a1d414ea319ff8953a4f6.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Londhe M, Garg S, Gurwale S, Gore C. Cystic presentation of primary hepatic neuroendocrine tumour: a case report with a brief review of literature. Explor Target Antitumor Ther. 2023;4:266–72. https://doi.org/10.37349/etat.2023.00133 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-04-25 02:29:35 [Bib_Time] => 2023-04-25 02:29:35 [KeysWordContens] => Cystic presentation of primary hepatic neuroendocrine tumour: a case report with a brief review of literature, Biliary, cystadenoma, primary neoplasm, synaptophysin, Neuroendocrine tumours (NETs) are a rare type of tumours that arise from the neuroendocrine cells which are distributed throughout the body. Of all the gastrointestinal tumours only 1–2% account for NETs. They have an extremely low incidence of 0.17% arising in the intrahepatic bile duct epithelium. Majority of hepatic NETs occur as a result of metastases from the primary NETs. Most cases of primary hepatic NET (PHNET) present as a solid nodular mass. However, predominantly cystic PHNET is extremely rare which mimics other cystic space-occupying lesions clinically and radiologically as seen in this case. ,Mangesh Londhe ... Charusheela Gore [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 1 ) [133] => Array ( [ArticleId] => 553 [Create_Time] => 2023-04-26 [zipUrl] => https://www.explorationpub.com/uploads/zip/202304/20230426074947.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002132/1002132.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002132/1002132.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002132/1002132_cover.png [JournalsId] => 4 [Title] => Gut microbiota, an emergent target to shape the efficiency of cancer therapy [Abstract] => It is now well-acknowledged that microbiota has a profound influence on both human health and illness. The gut microbiota has recently come to light as a crucial element that influences cancer throu [AbstractComplete] =>It is now well-acknowledged that microbiota has a profound influence on both human health and illness. The gut microbiota has recently come to light as a crucial element that influences cancer through a variety of mechanisms. The connections between the microbiome and cancer therapy are further highlighted by a number of preclinical and clinical evidence, suggesting that these complicated interactions may vary by cancer type, treatment, or even by tumor stage. The paradoxical relationship between gut microbiota and cancer therapies is that in some cancers, the gut microbiota may be necessary to maintain therapeutic efficacy, whereas, in other cancers, gut microbiota depletion significantly increases efficacy. Actually, mounting research has shown that the gut microbiota plays a crucial role in regulating the host immune response and boosting the efficacy of anticancer medications like chemotherapy and immunotherapy. Therefore, gut microbiota modulation, which aims to restore gut microbial balance, is a viable technique for cancer prevention and therapy given the expanding understanding of how the gut microbiome regulates treatment response and contributes to carcinogenesis. This review will provide an outline of the gut microbiota’s role in health and disease, along with a summary of the most recent research on how it may influence the effectiveness of various anticancer medicines and affect the growth of cancer. This study will next cover the newly developed microbiota-targeting strategies including prebiotics, probiotics, and fecal microbiota transplantation (FMT) to enhance anticancer therapy effectiveness, given its significance.
[Names] => Soumaya Kouidhi ... Amel Ben Ammar El Gaaied [Doi] => 10.37349/etat.2023.00132 [Published] => April 26, 2023 [Viewed] => 1271 [Downloaded] => 38 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00132 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 70 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:240–265 [Recommend] => 0 [Keywords] => Cancer, gut microbiota, dysbiosis, chemotherapy, immunotherapy [DetailTitle] => Cancer Immunotherapy and Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/70 [Id] => 1002132 [ris] => https://www.explorationpub.com/uploads/Article/A1002132/447e9dfccd0f4f5d4b3fafa14dccdbe1.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002132/6a735cab9d43b10d1aa312efd9a57473.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-26 [CitethisArticle] => Kouidhi S, Zidi O, Belkhiria Z, Rais H, Ayadi A, Ben Ayed F, et al. Gut microbiota, an emergent target to shape the efficiency of cancer therapy. Explor Target Antitumor Ther. 2023;4:240–65. https://doi.org/10.37349/etat.2023.00132 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-04-25 05:03:10 [Bib_Time] => 2023-04-25 05:03:10 [KeysWordContens] => Gut microbiota, an emergent target to shape the efficiency of cancer therapy, Cancer, gut microbiota, dysbiosis, chemotherapy, immunotherapy, It is now well-acknowledged that microbiota has a profound influence on both human health and illness. The gut microbiota has recently come to light as a crucial element that influences cancer through a variety of mechanisms. The connections between the microbiome and cancer therapy are further highlighted by a number of preclinical and clinical evidence, suggesting that these complicated interactions may vary by cancer type, treatment, or even by tumor stage. The paradoxical relationship between gut microbiota and cancer therapies is that in some cancers, the gut microbiota may be necessary to maintain therapeutic efficacy, whereas, in other cancers, gut microbiota depletion significantly increases efficacy. Actually, mounting research has shown that the gut microbiota plays a crucial role in regulating the host immune response and boosting the efficacy of anticancer medications like chemotherapy and immunotherapy. Therefore, gut microbiota modulation, which aims to restore gut microbial balance, is a viable technique for cancer prevention and therapy given the expanding understanding of how the gut microbiome regulates treatment response and contributes to carcinogenesis. This review will provide an outline of the gut microbiota’s role in health and disease, along with a summary of the most recent research on how it may influence the effectiveness of various anticancer medicines and affect the growth of cancer. This study will next cover the newly developed microbiota-targeting strategies including prebiotics, probiotics, and fecal microbiota transplantation (FMT) to enhance anticancer therapy effectiveness, given its significance. ,Soumaya Kouidhi ... Amel Ben Ammar El Gaaied [PublishedText] => Published [IsEdit] => 0 [AccountId] => 48 [Zh] => 1 ) [134] => Array ( [ArticleId] => 570 [Create_Time] => 2023-04-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202304/20230427082906.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002135/1002135.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002135/1002135.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002135/1002135_cover.png [JournalsId] => 4 [Title] => Development and validation of an infrared-artificial intelligence software for breast cancer detection [Abstract] => Aim: In countries where access to mammography equipment and skilled personnel is limited, most breast cancer (BC) cases are detected in locally advanced stages. Infrared breast thermography is reco [AbstractComplete] =>In countries where access to mammography equipment and skilled personnel is limited, most breast cancer (BC) cases are detected in locally advanced stages. Infrared breast thermography is recognized as an adjunctive technique for the detection of BC due to its advantages such as safety (by not emitting ionizing radiation nor applying any stress to the breast), portability, and low cost. Improved by advanced computational analytics techniques, infrared thermography could be a valuable complementary screening technique to detect BC at early stages. In this work, an infrared-artificial intelligence (AI) software was developed and evaluated to help physicians to identify potential BC cases.
Several AI algorithms were developed and evaluated, which were learned from a proprietary database of 2,700 patients, with BC cases that were confirmed through mammography, ultrasound, and biopsy. Following by evaluation of the algorithms, the best AI algorithm (infrared-AI software) was submitted to a clinic validation process in which its ability to detect BC was compared to mammography evaluations in a double-blind test.
The infrared-AI software demonstrated efficiency values of 94.87% sensitivity, 72.26% specificity, 30.08% positive predictive value (PPV), and 99.12% negative predictive value (NPV), whereas the reference mammography evaluation reached 100% sensitivity, 97.10% specificity, 81.25% PPV, and 100% NPV.
The infrared-AI software here developed shows high BC sensitivity (94.87%) and high NPV (99.12%). Therefore, it is proposed as a complementary screening tool for BC.
One in eight fatalities globally are considered cancer-related. The need for cancer therapy is growing. Natural products continue to play a role in drug development, as up to 50% of authorized drugs in the last 30 years have been isolated from natural sources.
Anticancer, antioxidant, antibacterial, antifungal, antiviral, analgesic, anti-inflammatory, and other actions have all been reported in research papers using plants from the Syzygium genus in the treatment and prevention of disease.
Results from the anticancer test showed that the genus, especially Syzygium aqueum, Syzygium samarangense, and Syzygium cumini had significant promise as an anticancer agent in vitro against several cancer cell lines. Numerous factors, including phytochemical composition, increased apoptotic activity, decreased cell proliferation, stopped angiogenesis, and reduced inflammation.
These results, despite preliminary, show promise for further purification and investigation of bioactive compounds and extracts within the genus Syzygium for their anticancer properties.
A clinical case of a 61-year-old female diagnosed with stage IV right colon adenocarcinoma (unresectable liver and multiple lymph node metastases at the time of diagnosis), Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma rat sarcoma viral oncogene homolog (NRAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type, proficient mismatch repair (pMMR), in whom a complete response to the third-line of systemic treatment with trifluridine/tipiracil (TAS-102) was obtained. The complete response has been maintained for more than 2 years after its suspension.
[Names] => Celia Lara-Morga ... Luis Cabezón-Gutiérrez [Doi] => 10.37349/etat.2023.00136 [Published] => April 27, 2023 [Viewed] => 718 [Downloaded] => 19 [Subject] => Case Report [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00136 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 103 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:307–315 [Recommend] => 0 [Keywords] => Complete response, colorectal cancer, trifluridine/tipiracil (TAS-102) [DetailTitle] => Biomarkers for Personalized and Precise Cancer Diagnosis and Treatment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/103 [Id] => 1002136 [ris] => https://www.explorationpub.com/uploads/Article/A1002136/a47214ba9a5b9b6ccaee5840710419f8.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002136/21c03e750a2f0ef1c4224718d754fb0a.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Lara-Morga C, Palka-Kotlowska M, Custodio-Cabello S, Pacheco-Barcia V, Cabezón-Gutiérrez L. Complete response to third-line treatment with trifluridine/tipiracil (TAS-102) in stage IV colon adenocarcinoma. Explor Target Antitumor Ther. 2023;4:307–15. https://doi.org/10.37349/etat.2023.00136 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-04-26 06:26:03 [Bib_Time] => 2023-04-26 06:26:03 [KeysWordContens] => Complete response to third-line treatment with trifluridine/tipiracil (TAS-102) in stage IV colon adenocarcinoma, Complete response, colorectal cancer, trifluridine/tipiracil (TAS-102), A clinical case of a 61-year-old female diagnosed with stage IV right colon adenocarcinoma (unresectable liver and multiple lymph node metastases at the time of diagnosis), Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma rat sarcoma viral oncogene homolog (NRAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type, proficient mismatch repair (pMMR), in whom a complete response to the third-line of systemic treatment with trifluridine/tipiracil (TAS-102) was obtained. The complete response has been maintained for more than 2 years after its suspension. ,Celia Lara-Morga ... Luis Cabezón-Gutiérrez [PublishedText] => Published [IsEdit] => 0 [AccountId] => 45 [Zh] => 1 ) [137] => Array ( [ArticleId] => 572 [Create_Time] => 2023-04-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202304/20230428060139.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002137/1002137.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002137/1002137.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002137/1002137_cover.png [JournalsId] => 4 [Title] => Transforming growth factor-β signaling: from tumor microenvironment to anticancer therapy [Abstract] => Transforming growth factor-β (TGF-β) signaling is an important pathway for promoting the pathogenesis of inflammatory diseases, including cancer. The roles of TGF-β signaling are heterogeneous and versatile in cancer development and progression, both anticancer and protumoral actions are reported. Interestingly, increasing evidence suggests that TGF-β enhances disease progression and drug resistance via immune-modulatory actions in the tumor microenvironment (TME) of solid tumors. A better understanding of its regulatory mechanisms in the TME at the molecular level can facilitate the development of precision medicine to block the protumoral actions of TGF-β in the TME. Here, the latest information about the regulatory mechanisms and translational research of TGF-β signaling in the TME for therapeutic development had been summarized. [AbstractComplete] =>Transforming growth factor-β (TGF-β) signaling is an important pathway for promoting the pathogenesis of inflammatory diseases, including cancer. The roles of TGF-β signaling are heterogeneous and versatile in cancer development and progression, both anticancer and protumoral actions are reported. Interestingly, increasing evidence suggests that TGF-β enhances disease progression and drug resistance via immune-modulatory actions in the tumor microenvironment (TME) of solid tumors. A better understanding of its regulatory mechanisms in the TME at the molecular level can facilitate the development of precision medicine to block the protumoral actions of TGF-β in the TME. Here, the latest information about the regulatory mechanisms and translational research of TGF-β signaling in the TME for therapeutic development had been summarized.
[Names] => Max Kam-Kwan Chan ... Patrick Ming-Kuen Tang [Doi] => 10.37349/etat.2023.00137 [Published] => April 28, 2023 [Viewed] => 1230 [Downloaded] => 48 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00137 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 70 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:316–343 [Recommend] => 0 [Keywords] => Transforming growth factor-β, tumor microenvironment, cancer, immunity, cancer immunotherapy [DetailTitle] => Cancer Immunotherapy and Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/70 [Id] => 1002137 [ris] => https://www.explorationpub.com/uploads/Article/A1002137/bc8736d6e122712aade3daf2b7f80e5b.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002137/9bb068187eaa685c21433e5dd3773f84.bib [ens] => [Cited] => 5 [Cited_Time] => 2024-04-26 [CitethisArticle] => Chan MKK, Chan ELY, Ji ZZ, Chan ASW, Li C, Leung KT, et al. Transforming growth factor-β signaling: from tumor microenvironment to anticancer therapy. Explor Target Antitumor Ther. 2023;4:316–43. https://doi.org/10.37349/etat.2023.00137 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-04-28 05:51:37 [Bib_Time] => 2023-04-28 05:51:37 [KeysWordContens] => Transforming growth factor-β signaling: from tumor microenvironment to anticancer therapy, Transforming growth factor-β, tumor microenvironment, cancer, immunity, cancer immunotherapy, Transforming growth factor-β (TGF-β) signaling is an important pathway for promoting the pathogenesis of inflammatory diseases, including cancer. The roles of TGF-β signaling are heterogeneous and versatile in cancer development and progression, both anticancer and protumoral actions are reported. Interestingly, increasing evidence suggests that TGF-β enhances disease progression and drug resistance via immune-modulatory actions in the tumor microenvironment (TME) of solid tumors. A better understanding of its regulatory mechanisms in the TME at the molecular level can facilitate the development of precision medicine to block the protumoral actions of TGF-β in the TME. Here, the latest information about the regulatory mechanisms and translational research of TGF-β signaling in the TME for therapeutic development had been summarized. ,Max Kam-Kwan Chan ... Patrick Ming-Kuen Tang [PublishedText] => Published [IsEdit] => 0 [AccountId] => 46 [Zh] => 1 ) [138] => Array ( [ArticleId] => 574 [Create_Time] => 2023-04-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202304/20230428053820.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002138/1002138.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002138/1002138.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002138/1002138_cover.png [JournalsId] => 4 [Title] => Role of artificial intelligence in oncologic emergencies: a narrative review [Abstract] => Oncologic emergencies are a wide spectrum of oncologic conditions caused directly by malignancies or their treatment. Oncologic emergencies may be classified according to the underlying physiopathol [AbstractComplete] =>Oncologic emergencies are a wide spectrum of oncologic conditions caused directly by malignancies or their treatment. Oncologic emergencies may be classified according to the underlying physiopathology in metabolic, hematologic, and structural conditions. In the latter, radiologists have a pivotal role, through an accurate diagnosis useful to provide optimal patient care. Structural conditions may involve the central nervous system, thorax, or abdomen, and emergency radiologists have to know the characteristics imaging findings of each one of them. The number of oncologic emergencies is growing due to the increased incidence of malignancies in the general population and also to the improved survival of these patients thanks to the advances in cancer treatment. Artificial intelligence (AI) could be a solution to assist emergency radiologists with this rapidly increasing workload. To our knowledge, AI applications in the setting of the oncologic emergency are mostly underexplored, probably due to the relatively low number of oncologic emergencies and the difficulty in training algorithms. However, cancer emergencies are defined by the cause and not by a specific pattern of radiological symptoms and signs. Therefore, it can be expected that AI algorithms developed for the detection of these emergencies in the non-oncological field can be transferred to the clinical setting of oncologic emergency. In this review, a craniocaudal approach was followed and central nervous system, thoracic, and abdominal oncologic emergencies have been addressed regarding the AI applications reported in literature. Among the central nervous system emergencies, AI applications have been reported for brain herniation and spinal cord compression. In the thoracic district the addressed emergencies were pulmonary embolism, cardiac tamponade and pneumothorax. Pneumothorax was the most frequently described application for AI, to improve sensibility and to reduce the time-to-diagnosis. Finally, regarding abdominal emergencies, AI applications for abdominal hemorrhage, intestinal obstruction, intestinal perforation, and intestinal intussusception have been described.
[Names] => Salvatore Claudio Fanni ... Emanuele Neri [Doi] => 10.37349/etat.2023.00138 [Published] => April 28, 2023 [Viewed] => 1133 [Downloaded] => 37 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00138 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 88 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:344–354 [Recommend] => 0 [Keywords] => Artificial intelligence, machine learning, deep learning, neural networks, oncologic emergencies, oncologic imaging [DetailTitle] => Artificial Intelligence for Precision Oncology [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/88 [Id] => 1002138 [ris] => https://www.explorationpub.com/uploads/Article/A1002138/0cdc570967fc0887aff15d2fefe92221.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002138/a907b91904dc130bc0217386310b188d.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-26 [CitethisArticle] => Fanni SC, Greco G, Rossi S, Aghakhanyan G, Masala S, Scaglione M, et al. Role of artificial intelligence in oncologic emergencies: a narrative review. Explor Target Antitumor Ther. 2023;4:344–54. https://doi.org/10.37349/etat.2023.00138 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-04-26 10:11:20 [Bib_Time] => 2023-04-26 10:11:20 [KeysWordContens] => Role of artificial intelligence in oncologic emergencies: a narrative review, Artificial intelligence, machine learning, deep learning, neural networks, oncologic emergencies, oncologic imaging, Oncologic emergencies are a wide spectrum of oncologic conditions caused directly by malignancies or their treatment. Oncologic emergencies may be classified according to the underlying physiopathology in metabolic, hematologic, and structural conditions. In the latter, radiologists have a pivotal role, through an accurate diagnosis useful to provide optimal patient care. Structural conditions may involve the central nervous system, thorax, or abdomen, and emergency radiologists have to know the characteristics imaging findings of each one of them. The number of oncologic emergencies is growing due to the increased incidence of malignancies in the general population and also to the improved survival of these patients thanks to the advances in cancer treatment. Artificial intelligence (AI) could be a solution to assist emergency radiologists with this rapidly increasing workload. To our knowledge, AI applications in the setting of the oncologic emergency are mostly underexplored, probably due to the relatively low number of oncologic emergencies and the difficulty in training algorithms. However, cancer emergencies are defined by the cause and not by a specific pattern of radiological symptoms and signs. Therefore, it can be expected that AI algorithms developed for the detection of these emergencies in the non-oncological field can be transferred to the clinical setting of oncologic emergency. In this review, a craniocaudal approach was followed and central nervous system, thoracic, and abdominal oncologic emergencies have been addressed regarding the AI applications reported in literature. Among the central nervous system emergencies, AI applications have been reported for brain herniation and spinal cord compression. In the thoracic district the addressed emergencies were pulmonary embolism, cardiac tamponade and pneumothorax. Pneumothorax was the most frequently described application for AI, to improve sensibility and to reduce the time-to-diagnosis. Finally, regarding abdominal emergencies, AI applications for abdominal hemorrhage, intestinal obstruction, intestinal perforation, and intestinal intussusception have been described. ,Salvatore Claudio Fanni ... Emanuele Neri [PublishedText] => Published [IsEdit] => 0 [AccountId] => 38 [Zh] => 1 ) [139] => Array ( [ArticleId] => 586 [Create_Time] => 2023-04-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202304/20230428082943.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002139/1002139.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002139/1002139.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002139/1002139_cover.png [JournalsId] => 4 [Title] => Small cell lung cancer: circulating tumor cell lines and expression of mediators of angiogenesis and coagulation [Abstract] => Aim: Coagulation is frequently activated in cancer patients and has been correlated with an unfavorable prognosis. To evaluate whether a putative release of tissue factor (TF) by circulating tumor [AbstractComplete] =>Coagulation is frequently activated in cancer patients and has been correlated with an unfavorable prognosis. To evaluate whether a putative release of tissue factor (TF) by circulating tumor cells (CTCs) represents a target to impair the dissemination of small cell lung cancer (SCLC), the expression of relevant proteins in a panel of permanent SCLC and SCLC CTC cell lines that have been established at the Medical University of Vienna.
Five CTC and SCLC lines were analyzed using a TF enzyme-linked immunosorbent assay (ELISA) tests, RNA sequencing, and western blot arrays covering 55 angiogenic mediators. Furthermore, the influence of topotecan and epirubicin as well as hypoxia-like conditions on the expression of these mediators was investigated.
The results demonstrate that the SCLC CTC cell lines express no significant amounts of active TF but thrombospondin-1 (TSP-1), urokinase-type plasminogen activator receptor (uPAR), vascular endothelial-derived growth factor (VEGF) and angiopoietin-2 in two cases. The major difference between the SCLC and SCLC CTC cell lines found was the loss of the expression of angiogenin in the blood-derived CTC lines. Topotecan and epirubicin decreased the expression of VEGF, whereas hypoxia-like conditions upregulated VEGF.
Active TF capable of triggering coagulation seems not to be expressed in SCLC CTC cell lines in significant levels and, thus, CTC-derived TF seems dispensable for dissemination. Nevertheless, all CTC lines form large spheroids, termed tumorospheres, which may become trapped in clots of the microvasculature and extravasate in this supportive microenvironment. The contribution of clotting to the protection and dissemination of CTCs in SCLC may be different from other solid tumors such as breast cancer.
Cancer is the leading cause of death globally superseded only by cardiovascular diseases, and novel strategies to overcome therapeutic resistance against existing cancer treatments are urgently required. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with potent immunosuppressive capacity against well-established anti-tumour effectors such as natural killer cells (NK cells) and T cells thereby promoting cancer initiation and progression. Critically, MDSCs are readily identified in almost all tumour types and human cancer patients, and numerous studies in the past decade have recognised their role in contributing to therapeutic resistance against all four pillars of modern cancer treatment, namely surgery, chemotherapy, radiotherapy and immunotherapy. MDSCs suppress anti-tumour immunity through a plethora of mechanisms including the well-characterised arginase 1 (Arg1), inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS)-mediated pathways, along with several other more recently discovered. MDSCs are largely absent in healthy homeostatic states and predominantly exist in pathological conditions, making them attractive therapeutic targets. However, the lack of specific markers identified for MDSCs to date greatly hindered therapeutic development, and currently there are no clinically approved drugs that specifically target MDSCs. Methods to deplete MDSCs clinically and inhibit their immunosuppressive function will be crucial in advancing cancer treatment and to overcome treatment resistance. This review provides a detailed overview of the current understandings behind the mechanisms of MDSC-mediated suppression of anti-tumour immunity, and discusses potential strategies to target MDSC immunosuppressive mechanisms to overcome therapeutic resistance.
[Names] => Eric Jou ... Fizza Nasim [Doi] => 10.37349/etat.2024.00212 [Published] => February 28, 2024 [Viewed] => 763 [Downloaded] => 14 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00212 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 175 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:187–207 [Recommend] => 0 [Keywords] => Tumor microenvironment, cancer therapy, preclinical models, immunotherapy, myeloid-derived suppressor cell, myeloid cells, immunosuppression [DetailTitle] => Novel Strategies and Targets for Immunotherapy of Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/175 [Id] => 1002212 [ris] => https://www.explorationpub.com/uploads/Article/A1002212/accc3bd8156d8575eb304a6d6a73980c.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002212/89ab585970ca440e22df74b7a763ad81.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Jou E, Chaudhury N, Nasim F. Novel therapeutic strategies targeting myeloid-derived suppressor cell immunosuppressive mechanisms for cancer treatment. Explor Target Antitumor Ther. 2024;5:187–207. https://doi.org/10.37349/etat.2024.00212 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-19 06:57:30 [Bib_Time] => 2024-02-19 06:57:30 [KeysWordContens] => Novel therapeutic strategies targeting myeloid-derived suppressor cell immunosuppressive mechanisms for cancer treatment, Tumor microenvironment, cancer therapy, preclinical models, immunotherapy, myeloid-derived suppressor cell, myeloid cells, immunosuppression, Cancer is the leading cause of death globally superseded only by cardiovascular diseases, and novel strategies to overcome therapeutic resistance against existing cancer treatments are urgently required. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with potent immunosuppressive capacity against well-established anti-tumour effectors such as natural killer cells (NK cells) and T cells thereby promoting cancer initiation and progression. Critically, MDSCs are readily identified in almost all tumour types and human cancer patients, and numerous studies in the past decade have recognised their role in contributing to therapeutic resistance against all four pillars of modern cancer treatment, namely surgery, chemotherapy, radiotherapy and immunotherapy. MDSCs suppress anti-tumour immunity through a plethora of mechanisms including the well-characterised arginase 1 (Arg1), inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS)-mediated pathways, along with several other more recently discovered. MDSCs are largely absent in healthy homeostatic states and predominantly exist in pathological conditions, making them attractive therapeutic targets. However, the lack of specific markers identified for MDSCs to date greatly hindered therapeutic development, and currently there are no clinically approved drugs that specifically target MDSCs. Methods to deplete MDSCs clinically and inhibit their immunosuppressive function will be crucial in advancing cancer treatment and to overcome treatment resistance. This review provides a detailed overview of the current understandings behind the mechanisms of MDSC-mediated suppression of anti-tumour immunity, and discusses potential strategies to target MDSC immunosuppressive mechanisms to overcome therapeutic resistance. ,Eric Jou ... Fizza Nasim [PublishedText] => Published [IsEdit] => 0 [AccountId] => 22 [Zh] => 1 ) [141] => Array ( [ArticleId] => 607 [Create_Time] => 2023-06-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230629004133.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002140/1002140.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002140/1002140.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002140/1002140_cover.png [JournalsId] => 4 [Title] => Capitalizing glycomic changes for improved biomarker-based cancer diagnostics [Abstract] => Cancer serum biomarkers are valuable or even indispensable for cancer diagnostics and/or monitoring and, currently, many cancer serum markers are routinely used in the clinic. Most of those markers [AbstractComplete] =>Cancer serum biomarkers are valuable or even indispensable for cancer diagnostics and/or monitoring and, currently, many cancer serum markers are routinely used in the clinic. Most of those markers are glycoproteins, carrying cancer-specific glycan structures that can provide extra-information for cancer monitoring. Nonetheless, in the majority of cases, this differential feature is not exploited and the corresponding analytical assays detect only the protein amount, disregarding the analysis of the aberrant glycoform. Two exceptions to this trend are the biomarkers α-fetoprotein (AFP) and cancer antigen 19-9 (CA19-9), which are clinically monitored for their cancer-related glycan changes, and only the AFP assay includes quantification of both the protein amount and the altered glycoform. This narrative review demonstrates, through several examples, the advantages of the combined quantification of protein cancer biomarkers and the respective glycoform analysis, which enable to yield the maximum information and overcome the weaknesses of each individual analysis. This strategy allows to achieve higher sensitivity and specificity in the detection of cancer, enhancing the diagnostic power of biomarker-based cancer detection tests.
[Names] => Maria Luísa S. Silva [Doi] => 10.37349/etat.2023.00140 [Published] => June 28, 2023 [Viewed] => 618 [Downloaded] => 24 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00140 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 103 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:366–395 [Recommend] => 0 [Keywords] => Cancer, biomarkers, aberrant glycosylation, assays, sensitivity, specificity [DetailTitle] => Biomarkers for Personalized and Precise Cancer Diagnosis and Treatment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/103 [Id] => 1002140 [ris] => https://www.explorationpub.com/uploads/Article/A1002140/b871a6e1435d16577b9641e805d4fc7e.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002140/5fe21dc642dc867e89b871d3bd82c060.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-27 [CitethisArticle] => Maria Luísa S. Silva. Capitalizing glycomic changes for improved biomarker-based cancer diagnostics. Explor Target Antitumor Ther. 2023;4:366–95. https://doi.org/10.37349/etat.2023.00140 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-06-28 09:35:19 [Bib_Time] => 2023-06-28 09:35:19 [KeysWordContens] => Capitalizing glycomic changes for improved biomarker-based cancer diagnostics, Cancer, biomarkers, aberrant glycosylation, assays, sensitivity, specificity, Cancer serum biomarkers are valuable or even indispensable for cancer diagnostics and/or monitoring and, currently, many cancer serum markers are routinely used in the clinic. Most of those markers are glycoproteins, carrying cancer-specific glycan structures that can provide extra-information for cancer monitoring. Nonetheless, in the majority of cases, this differential feature is not exploited and the corresponding analytical assays detect only the protein amount, disregarding the analysis of the aberrant glycoform. Two exceptions to this trend are the biomarkers α-fetoprotein (AFP) and cancer antigen 19-9 (CA19-9), which are clinically monitored for their cancer-related glycan changes, and only the AFP assay includes quantification of both the protein amount and the altered glycoform. This narrative review demonstrates, through several examples, the advantages of the combined quantification of protein cancer biomarkers and the respective glycoform analysis, which enable to yield the maximum information and overcome the weaknesses of each individual analysis. This strategy allows to achieve higher sensitivity and specificity in the detection of cancer, enhancing the diagnostic power of biomarker-based cancer detection tests. ,Maria Luísa S. Silva [PublishedText] => Published [IsEdit] => 0 [AccountId] => 57 [Zh] => 1 ) [142] => Array ( [ArticleId] => 608 [Create_Time] => 2023-06-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230629054210.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002141/1002141.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002141/1002141.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002141/etat-04-1002141_cover.png [JournalsId] => 4 [Title] => Real world outcomes in patients with neuroendocrine tumor receiving peptide receptor radionucleotide therapy [Abstract] => Aim: 177Lu-Dotatate (Lu-177), a form of peptide receptor radionuclide therapy (PRRT), was approved by Food and Drug Administration (FDA) for the treatment of somatostatin-receptor-positive neur [AbstractComplete] =>177Lu-Dotatate (Lu-177), a form of peptide receptor radionuclide therapy (PRRT), was approved by Food and Drug Administration (FDA) for the treatment of somatostatin-receptor-positive neuroendocrine tumors (NETs) in 2018. Clinical trials prior to the FDA approval of Lu-177 showed favorable outcomes but there is limited published real world outcomes data. This study aims to describe and analyze real world outcomes of patients with NET who received Lu-177.
After obtaining institutional review board approval, retrospective evaluation was performed to analyze the efficacy of Lu-177 for somatostatin receptor-positive gastro-entero-pancreatic NETs (GEP-NETs) patients at the University of Kansas Cancer Center between June 2018 and September 2021. This study aims to determine the response rate to the treatment of the entire cohort and subgroups.
A total of 65 patients received Lu-177 of which 58 completed treatment. The 58 patients had a median age of 61.5 years, 24 females and 34 males, 86% Caucasian and 12% black. The origins of NETs were primarily small bowel (n = 24) and pancreatic (n = 14). Pathology showed grades 1 (n = 21), 2 (n = 25), and 3 (n = 4) and were primarily well-differentiated tumors (n = 4). Among the cohort, 52 patients had imaging to assess response with 14 (26.9%) patients with partial response (PR), 31 (59.6%) with stable disease (SD), and 7 (13.5%) with progressive disease (PD). In a subset analysis, patients with non-functional disease (n = 29) had higher rates of PR 42.3% (compared to 11.5%, P = 0.0147) and higher disease control rate of 96% (compared to 78%, P = 0.042) than patients with functional disease (n = 29). Patients with non-functional disease had a lower PD of 3.85% (compared to 23%, P = 0.0147) than those with functional disease.
This real world outcomes analysis of NETs treated with Lu-177 shows improved PR when compared to the initial clinical trials and is promising for patients. In addition, patients with non-functional tumors were found to have a statistically significant improved response rate which has not been described in the literature before. If these study findings are validated in a larger cohort they may guide patient selection for Lu-177 therapy in the future.
Rectal cancer (RC) is one of the most common tumours worldwide in both males and females, with significant morbidity and mortality rates, and it accounts for approximately one-third of colorectal cancers (CRCs). Magnetic resonance imaging (MRI) has been demonstrated to be accurate in evaluating the tumour location and stage, mucin content, invasion depth, lymph node (LN) metastasis, extramural vascular invasion (EMVI), and involvement of the mesorectal fascia (MRF). However, these features alone remain insufficient to precisely guide treatment decisions. Therefore, new imaging biomarkers are necessary to define tumour characteristics for staging and restaging patients with RC. During the last decades, RC evaluation via MRI-based radiomics and artificial intelligence (AI) tools has been a research hotspot. The aim of this review was to summarise the achievement of MRI-based radiomics and AI for the evaluation of staging, response to therapy, genotyping, prediction of high-risk factors, and prognosis in the field of RC. Moreover, future challenges and limitations of these tools that need to be solved to favour the transition from academic research to the clinical setting will be discussed.
[Names] => Giuseppe Di Costanzo ... Enrico Cavaglià [Doi] => 10.37349/etat.2023.00142 [Published] => June 30, 2023 [Viewed] => 822 [Downloaded] => 23 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00142 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 88 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:406–421 [Recommend] => 0 [Keywords] => Rectal cancer, magnetic resonance imaging, radiomics, machine learning, artificial intelligence [DetailTitle] => Artificial Intelligence for Precision Oncology [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/88 [Id] => 1002142 [ris] => https://www.explorationpub.com/uploads/Article/A1002142/3632cfd11d8437a3c11b5318c904fc2a.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002142/d2ac32db0f272f9ca8fc3f95a6051fcb.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-27 [CitethisArticle] => Di Costanzo G, Ascione R, Ponsiglione A, Tucci AG, Dell’Aversana S, Iasiello F, et al. Artificial intelligence and radiomics in magnetic resonance imaging of rectal cancer: a review. Explor Target Antitumor Ther. 2023;4:406–21. https://doi.org/10.37349/etat.2023.00142 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-06-29 08:15:00 [Bib_Time] => 2023-06-29 08:15:00 [KeysWordContens] => Artificial intelligence and radiomics in magnetic resonance imaging of rectal cancer: a review, Rectal cancer, magnetic resonance imaging, radiomics, machine learning, artificial intelligence, Rectal cancer (RC) is one of the most common tumours worldwide in both males and females, with significant morbidity and mortality rates, and it accounts for approximately one-third of colorectal cancers (CRCs). Magnetic resonance imaging (MRI) has been demonstrated to be accurate in evaluating the tumour location and stage, mucin content, invasion depth, lymph node (LN) metastasis, extramural vascular invasion (EMVI), and involvement of the mesorectal fascia (MRF). However, these features alone remain insufficient to precisely guide treatment decisions. Therefore, new imaging biomarkers are necessary to define tumour characteristics for staging and restaging patients with RC. During the last decades, RC evaluation via MRI-based radiomics and artificial intelligence (AI) tools has been a research hotspot. The aim of this review was to summarise the achievement of MRI-based radiomics and AI for the evaluation of staging, response to therapy, genotyping, prediction of high-risk factors, and prognosis in the field of RC. Moreover, future challenges and limitations of these tools that need to be solved to favour the transition from academic research to the clinical setting will be discussed. ,Giuseppe Di Costanzo ... Enrico Cavaglià [PublishedText] => Published [IsEdit] => 0 [AccountId] => 24 [Zh] => 1 ) [144] => Array ( [ArticleId] => 621 [Create_Time] => 2023-06-30 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230630093116.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002143/1002143.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002143/1002143.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002143/1002143_cover.png [JournalsId] => 4 [Title] => Liquid biopsy: an examination of platelet RNA obtained from head and neck squamous cell carcinoma patients for predictive molecular tumor markers [Abstract] => Aim: Recently, a tumor cell-platelet interaction was identified in different tumor entities, resulting in a transfer of tumor-derived RNA into platelets, named further “tumor-educated platelets [AbstractComplete] =>Recently, a tumor cell-platelet interaction was identified in different tumor entities, resulting in a transfer of tumor-derived RNA into platelets, named further “tumor-educated platelets (TEP)”. The present pilot study aims to investigate whether such a tumor-platelet transfer of RNA occurs also in patients suffering from head and neck squamous cell carcinoma (HNSCC).
Sequencing analysis of RNA derived from platelets of tumor patients (TPs) and healthy donors (HDs) were performed. Subsequently, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used for verification of differentially expressed genes in platelets from TPs and HDs in a second cohort of patients and HDs. Data were analyzed by applying bioinformatic tools.
Sequencing of RNA derived from the tumor as well as from platelets of TPs and HDs revealed 426 significantly differentially existing RNA, at which 406 RNA were more and 20 RNA less abundant in platelets from TPs in comparison to that of HDs. In TPs’ platelets, abundantly existing RNA coding for 49 genes were detected, characteristically expressed in epithelial cells and RNA, the products of which are involved in tumor progression. Applying bioinformatic tools and verification on a second TP/HD cohort, collagen type I alpha 1 chain (COL1A1) and zinc finger protein 750 (ZNF750) were identified as the strongest potentially platelet-RNA-sequencing (RNA-seq)-based biomarkers for HNSCC.
These results indicate a transfer of tumor-derived messenger RNA (mRNA) into platelets of HNSCC patients. Therefore, analyses of a patient’s platelet RNA could be an efficient option for liquid biopsy in order to diagnose HNSCC or to monitor tumorigenesis as well as therapeutic responses at any time and in real time.
Human histone deacetylase 8 (KDAC8) is a well-recognized pharmaceutical target in Cornelia de Lange syndrome and different types of cancer, particularly childhood neuroblastoma. Several classes of chemotypes have been identified, which interfere with the enzyme activity of KDAC8. These compounds have been identified under equilibrium or near equilibrium conditions for inhibitor binding to the target enzyme. This study aims for the classification of KDAC8 inhibitors according to the mode of action and identification of most promising lead compounds for drug development.
A continuous enzyme activity assay is used to monitor inhibition kinetics.
A high-throughput continuous KDAC8 activity assay is developed that provides additional mechanistic information about enzyme inhibition enabling the classification of KDAC8 inhibitors according to their mode of action. Fast reversible inhibitors act as a molecular chaperone and are capable to rescue the enzyme activity of misfolded KDAC8, while covalent inactivators and slow dissociating inhibitors do not preserve KDAC8 activity.
The application of continuous KDAC8 activity assay reveals additional information about the mode of interaction with inhibitors, which can be used to classify KDAC8 inhibitors according to their mode of action. The approach is compatible with the high-throughput screening of compound libraries. Fast reversible inhibitors of KDAC8 act as molecular chaperones and recover enzyme activity from misfolded protein conformations. In contrast, slow-binding inhibitors and covalent inactivators of KDAC8 are not capable to recover enzyme activity.
Immunotherapy strategies targeting immune checkpoint molecules such as programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) are revolutionizing oncology. However, its effectiveness is limited in part due to the loss of effector cytotoxic T lymphocytes. Interestingly, supplementation of vitamin D could abolish the repressive effect of programmed cell death-ligand 1 (PD-L1) on CD8+ T cells, which might prevent the lymphocytopenia. In addition, vitamin D signaling could contribute to the differentiation of T-regulatory (Treg) cells associated with the expression of Treg markers such as forkhead box P3 (FOXP3) and CTLA-4. Furthermore, vitamin D may be associated with the stimulation of innate immunity. Peroxisome proliferator-activated receptor (PPAR) and estrogen receptor (ESR) signaling, and even the signaling from phosphoinositide-3 kinase (PI3K)/AKT pathway could have inhibitory roles in carcinogenesis possibly via the modulation of immune checkpoint molecules. In some cases, certain small molecules including vitamin D could be a novel therapeutic modality with a promising potential for the better performance of immune checkpoint blockade cancer therapies.
[Names] => Ai Tsuji ... Satoru Matsuda [Doi] => 10.37349/etat.2023.00145 [Published] => June 30, 2023 [Viewed] => 1779 [Downloaded] => 800 [Subject] => Perspective [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00145 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 70 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:460–473 [Recommend] => 0 [Keywords] => Vitamin D, programmed cell death-1 (PD-1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), immune checkpoint, estrogen, peroxisome proliferator-activated receptor (PPAR), phosphoinositide-3 kinase (PI3K)/AKT, cancer therapy [DetailTitle] => Cancer Immunotherapy and Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/70 [Id] => 1002145 [ris] => https://www.explorationpub.com/uploads/Article/A1002145/24e68fd039bc29514caded137b1db20a.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002145/67b6aeef0c2de2eba1e5047b406666e8.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Tsuji A, Yoshikawa S, Morikawa S, Ikeda Y, Taniguchi K, Sawamura H, et al. Potential tactics with vitamin D and certain phytochemicals for enhancing the effectiveness of immune-checkpoint blockade therapies. Explor Target Antitumor Ther. 2023;4:460–73. https://doi.org/10.37349/etat.2023.00145 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-06-28 03:44:30 [Bib_Time] => 2023-06-28 03:44:30 [KeysWordContens] => Potential tactics with vitamin D and certain phytochemicals for enhancing the effectiveness of immune-checkpoint blockade therapies, Vitamin D, programmed cell death-1 (PD-1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), immune checkpoint, estrogen, peroxisome proliferator-activated receptor (PPAR), phosphoinositide-3 kinase (PI3K)/AKT, cancer therapy, Immunotherapy strategies targeting immune checkpoint molecules such as programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) are revolutionizing oncology. However, its effectiveness is limited in part due to the loss of effector cytotoxic T lymphocytes. Interestingly, supplementation of vitamin D could abolish the repressive effect of programmed cell death-ligand 1 (PD-L1) on CD8+ T cells, which might prevent the lymphocytopenia. In addition, vitamin D signaling could contribute to the differentiation of T-regulatory (Treg) cells associated with the expression of Treg markers such as forkhead box P3 (FOXP3) and CTLA-4. Furthermore, vitamin D may be associated with the stimulation of innate immunity. Peroxisome proliferator-activated receptor (PPAR) and estrogen receptor (ESR) signaling, and even the signaling from phosphoinositide-3 kinase (PI3K)/AKT pathway could have inhibitory roles in carcinogenesis possibly via the modulation of immune checkpoint molecules. In some cases, certain small molecules including vitamin D could be a novel therapeutic modality with a promising potential for the better performance of immune checkpoint blockade cancer therapies. ,Ai Tsuji ... Satoru Matsuda [PublishedText] => Published [IsEdit] => 0 [AccountId] => 24 [Zh] => 1 ) [147] => Array ( [ArticleId] => 625 [Create_Time] => 2023-07-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230630051440.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002146/1002146.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002146/1002146.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002146/1002146_cover.png [JournalsId] => 4 [Title] => Type 1 and type 2 cytokine-mediated immune orchestration in the tumour microenvironment and their therapeutic potential [Abstract] => Cancer remains the second leading cause of death worldwide despite modern breakthroughs in medicine, and novel treatments are urgently needed. The revolutionary success of immune checkpoint inhibito [AbstractComplete] =>Cancer remains the second leading cause of death worldwide despite modern breakthroughs in medicine, and novel treatments are urgently needed. The revolutionary success of immune checkpoint inhibitors in the past decade serves as proof of concept that the immune system can be effectively harnessed to treat cancer. Cytokines are small signalling proteins with critical roles in orchestrating the immune response and have become an attractive target for immunotherapy. Type 1 immune cytokines, including interferon γ (IFNγ), interleukin-12 (IL-12), and tumour necrosis factor α (TNFα), have been shown to have largely tumour suppressive roles in part through orchestrating anti-tumour immune responses mediated by natural killer (NK) cells, CD8+ T cells and T helper 1 (Th1) cells. Conversely, type 2 immunity involving group 2 innate lymphoid cells (ILC2s) and Th2 cells are involved in tissue regeneration and wound repair and are traditionally thought to have pro-tumoural effects. However, it is found that the classical type 2 immune cytokines IL-4, IL-5, IL-9, and IL-13 may have conflicting roles in cancer. Similarly, type 2 immunity-related cytokines IL-25 and IL-33 with recently characterised roles in cancer may either promote or suppress tumorigenesis in a context-dependent manner. Furthermore, type 1 cytokines IFNγ and TNFα have also been found to have pro-tumoural effects under certain circumstances, further complicating the overall picture. Therefore, the dichotomy of type 1 and type 2 cytokines inhibiting and promoting tumours respectively is not concrete, and attempts of utilising these for cancer immunotherapy must take into account all available evidence. This review provides an overview summarising the current understanding of type 1 and type 2 cytokines in tumour immunity and discusses the prospects of harnessing these for immunotherapy in light of previous and ongoing clinical trials.
[Names] => Eric Jou [Doi] => 10.37349/etat.2023.00146 [Published] => June 30, 2023 [Viewed] => 785 [Downloaded] => 22 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00146 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 113 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:474–497 [Recommend] => 0 [Keywords] => Tumour microenvironment, cancer therapy, targeted therapy, preclinical models, immunotherapy, cytokines, oncology trials [DetailTitle] => Therapeutic Targeting of the Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/113 [Id] => 1002146 [ris] => https://www.explorationpub.com/uploads/Article/A1002146/a74aea7c69700fbbf6f7cc0f47716b00.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002146/83fb2ee73322a4073c4130a7d46a5729.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-26 [CitethisArticle] => Jou E. Type 1 and type 2 cytokine-mediated immune orchestration in the tumour microenvironment and their therapeutic potential. Explor Target Antitumor Ther. 2023;4:474–97. https://doi.org/10.37349/etat.2023.00146 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-06-30 02:59:18 [Bib_Time] => 2023-06-30 02:59:18 [KeysWordContens] => Type 1 and type 2 cytokine-mediated immune orchestration in the tumour microenvironment and their therapeutic potential, Tumour microenvironment, cancer therapy, targeted therapy, preclinical models, immunotherapy, cytokines, oncology trials, Cancer remains the second leading cause of death worldwide despite modern breakthroughs in medicine, and novel treatments are urgently needed. The revolutionary success of immune checkpoint inhibitors in the past decade serves as proof of concept that the immune system can be effectively harnessed to treat cancer. Cytokines are small signalling proteins with critical roles in orchestrating the immune response and have become an attractive target for immunotherapy. Type 1 immune cytokines, including interferon γ (IFNγ), interleukin-12 (IL-12), and tumour necrosis factor α (TNFα), have been shown to have largely tumour suppressive roles in part through orchestrating anti-tumour immune responses mediated by natural killer (NK) cells, CD8+ T cells and T helper 1 (Th1) cells. Conversely, type 2 immunity involving group 2 innate lymphoid cells (ILC2s) and Th2 cells are involved in tissue regeneration and wound repair and are traditionally thought to have pro-tumoural effects. However, it is found that the classical type 2 immune cytokines IL-4, IL-5, IL-9, and IL-13 may have conflicting roles in cancer. Similarly, type 2 immunity-related cytokines IL-25 and IL-33 with recently characterised roles in cancer may either promote or suppress tumorigenesis in a context-dependent manner. Furthermore, type 1 cytokines IFNγ and TNFα have also been found to have pro-tumoural effects under certain circumstances, further complicating the overall picture. Therefore, the dichotomy of type 1 and type 2 cytokines inhibiting and promoting tumours respectively is not concrete, and attempts of utilising these for cancer immunotherapy must take into account all available evidence. This review provides an overview summarising the current understanding of type 1 and type 2 cytokines in tumour immunity and discusses the prospects of harnessing these for immunotherapy in light of previous and ongoing clinical trials. ,Eric Jou [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 1 ) [148] => Array ( [ArticleId] => 636 [Create_Time] => 2023-07-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230630085532.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002148/1002148.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002148/1002148.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002148/1002148_cover.png [JournalsId] => 4 [Title] => Spontaneous regression of a metastatic carcinoma transmitted by a kidney graft [Abstract] => Transmission of a malignancy from a donor’s organ to the recipient of the graft is a rare event, though it is a severe complication that can result in a poor outcome. Usually, immunosuppressive th [AbstractComplete] =>Transmission of a malignancy from a donor’s organ to the recipient of the graft is a rare event, though it is a severe complication that can result in a poor outcome. Usually, immunosuppressive therapy is discontinued and the allograft is removed. However, treatment of patients with the disseminated cancers implies that after the graft removal and cessation of the immunosuppression, radiotherapy, chemotherapy, or immunotherapy with alpha-interferon (INF-α) or interleukin-2 (IL-2) are required. The case report presents a clinical case of a transmitted kidney graft with multiple metastases (MTS) in a 31-year-old woman with the spontaneous regression of the metastatic cancer after transplantectomy and cancellation of the immunosuppressive therapy. Obviously, the determining factor is the recognition of the tumor by the effectors of the antitumor immunity due to the human leukocyte antigen (HLA) mismatch between the donor and the recipient. Therefore, cancellation of the immunosuppressive therapy in cases of transferal of a malignancy with a transplanted organ allows the effectors of the immune system to distinguish the tumor as a foreign tissue and effectively eliminate this neoplasm.
[Names] => Mikhail V. Kiselevskiy ... Irina Zh. Shubina [Doi] => 10.37349/etat.2023.00148 [Published] => June 30, 2023 [Viewed] => 504 [Downloaded] => 15 [Subject] => Case Report [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00148 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:511–518 [Recommend] => 0 [Keywords] => Cancer, spontaneous regressions, kidney graft, immunosuppressive therapy [DetailTitle] => [DetailUrl] => [Id] => 1002148 [ris] => https://www.explorationpub.com/uploads/Article/A1002148/64c5a64bbfbd2ccdafba1be4db4c359a.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002148/0e32ee7dd500793152af7a3e249b87ce.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Kiselevskiy MV, Gromova EG, Kozlov NA, Bezhanova SD, Shubina IZ. Spontaneous regression of a metastatic carcinoma transmitted by a kidney graft. Explor Target Antitumor Ther. 2023;4:511–8. https://doi.org/10.37349/etat.2023.00148 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-06-29 05:06:30 [Bib_Time] => 2023-06-29 05:06:30 [KeysWordContens] => Spontaneous regression of a metastatic carcinoma transmitted by a kidney graft, Cancer, spontaneous regressions, kidney graft, immunosuppressive therapy, Transmission of a malignancy from a donor’s organ to the recipient of the graft is a rare event, though it is a severe complication that can result in a poor outcome. Usually, immunosuppressive therapy is discontinued and the allograft is removed. However, treatment of patients with the disseminated cancers implies that after the graft removal and cessation of the immunosuppression, radiotherapy, chemotherapy, or immunotherapy with alpha-interferon (INF-α) or interleukin-2 (IL-2) are required. The case report presents a clinical case of a transmitted kidney graft with multiple metastases (MTS) in a 31-year-old woman with the spontaneous regression of the metastatic cancer after transplantectomy and cancellation of the immunosuppressive therapy. Obviously, the determining factor is the recognition of the tumor by the effectors of the antitumor immunity due to the human leukocyte antigen (HLA) mismatch between the donor and the recipient. Therefore, cancellation of the immunosuppressive therapy in cases of transferal of a malignancy with a transplanted organ allows the effectors of the immune system to distinguish the tumor as a foreign tissue and effectively eliminate this neoplasm. ,Mikhail V. Kiselevskiy ... Irina Zh. Shubina [PublishedText] => Published [IsEdit] => 0 [AccountId] => 57 [Zh] => 1 ) [149] => Array ( [ArticleId] => 629 [Create_Time] => 2023-07-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230629105225.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002147/1002147.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002147/1002147.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002147/1002147_cover.png [JournalsId] => 4 [Title] => Increasing differential diagnosis between lipoma and liposarcoma through radiomics: a narrative review [Abstract] => Soft tissue sarcomas (STSs) are rare, heterogeneous, and very often asymptomatic diseases. Their diagnosis is fundamental, as is the identification of the degree of malignancy, which may be high, me [AbstractComplete] =>Soft tissue sarcomas (STSs) are rare, heterogeneous, and very often asymptomatic diseases. Their diagnosis is fundamental, as is the identification of the degree of malignancy, which may be high, medium, or low. The Italian Medical Oncology Association and European Society of Medical Oncology (ESMO) guidelines recommend magnetic resonance imaging (MRI) because the clinical examination is typically ineffective. The diagnosis of these rare diseases with artificial intelligence (AI) techniques presents reduced datasets and therefore less robust methods. However, the combination of AI techniques with radiomics may be a new angle in diagnosing rare diseases such as STSs. Results obtained are promising within the literature, not only for the performance but also for the explicability of the data. In fact, one can make tumor classification, site localization, and prediction of the risk of developing metastasis. Thanks to the synergy between computer scientists and radiologists, linking numerical features to radiological evidence with excellent performance could be a new step forward for the diagnosis of rare diseases.
[Names] => Raffaele Natella ... Antonella Santone [Doi] => 10.37349/etat.2023.00147 [Published] => June 30, 2023 [Viewed] => 800 [Downloaded] => 24 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00147 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 88 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:498–510 [Recommend] => 0 [Keywords] => Radiology, radiomics, soft tissue sarcomas, liposarcoma, magnetic resonance imaging [DetailTitle] => Artificial Intelligence for Precision Oncology [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/88 [Id] => 1002147 [ris] => https://www.explorationpub.com/uploads/Article/A1002147/0cc75f83c32bf32b5a67d102e14af441.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002147/ee4824811672e39e5c765348d33087df.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Natella R, Varriano G, Brunese MC, Zappia M, Bruno M, Gallo M, et al. Increasing differential diagnosis between lipoma and liposarcoma through radiomics: a narrative review. Explor Target Antitumor Ther. 2023;4:498–510. https://doi.org/10.37349/etat.2023.00147 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-06-29 08:56:16 [Bib_Time] => 2023-06-29 08:56:16 [KeysWordContens] => Increasing differential diagnosis between lipoma and liposarcoma through radiomics: a narrative review, Radiology, radiomics, soft tissue sarcomas, liposarcoma, magnetic resonance imaging, Soft tissue sarcomas (STSs) are rare, heterogeneous, and very often asymptomatic diseases. Their diagnosis is fundamental, as is the identification of the degree of malignancy, which may be high, medium, or low. The Italian Medical Oncology Association and European Society of Medical Oncology (ESMO) guidelines recommend magnetic resonance imaging (MRI) because the clinical examination is typically ineffective. The diagnosis of these rare diseases with artificial intelligence (AI) techniques presents reduced datasets and therefore less robust methods. However, the combination of AI techniques with radiomics may be a new angle in diagnosing rare diseases such as STSs. Results obtained are promising within the literature, not only for the performance but also for the explicability of the data. In fact, one can make tumor classification, site localization, and prediction of the risk of developing metastasis. Thanks to the synergy between computer scientists and radiologists, linking numerical features to radiological evidence with excellent performance could be a new step forward for the diagnosis of rare diseases. ,Raffaele Natella ... Antonella Santone [PublishedText] => Published [IsEdit] => 0 [AccountId] => 69 [Zh] => 1 ) [150] => Array ( [ArticleId] => 638 [Create_Time] => 2023-07-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230630061808.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002149/1002149.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002149/1002149.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002149/1002149_cover.png [JournalsId] => 4 [Title] => Glucose metabolism reprogramming promotes immune escape of hepatocellular carcinoma cells [Abstract] => Hepatocellular carcinoma (HCC) is a complex process that plays an important role in its progression. Abnormal glucose metabolism in HCC cells can meet the nutrients required for the occurrence and d [AbstractComplete] =>Hepatocellular carcinoma (HCC) is a complex process that plays an important role in its progression. Abnormal glucose metabolism in HCC cells can meet the nutrients required for the occurrence and development of liver cancer, better adapt to changes in the surrounding microenvironment, and escape the attack of the immune system on the tumor. There is a close relationship between reprogramming of glucose metabolism and immune escape. This article reviews the current status and progress of glucose metabolism reprogramming in promoting immune escape in liver cancer, aiming to provide new strategies for clinical immunotherapy of liver cancer.
[Names] => Qiuyue Zhang ... Mengsen Li [Doi] => 10.37349/etat.2023.00149 [Published] => June 30, 2023 [Viewed] => 872 [Downloaded] => 25 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00149 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 113 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:519–536 [Recommend] => 0 [Keywords] => Hepatocellular carcinoma, reprogramming of glucose metabolism, immune escape [DetailTitle] => Therapeutic Targeting of the Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/113 [Id] => 1002149 [ris] => https://www.explorationpub.com/uploads/Article/A1002149/fe34017459942e80838303af90dccfc4.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002149/39ef875ecf4694d81b8ae039f72af778.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Zhang Q, Liu J, Lin H, Lin B, Zhu M, Li M. Glucose metabolism reprogramming promotes immune escape of hepatocellular carcinoma cells. Explor Target Antitumor Ther. 2023;4:519–36. https://doi.org/10.37349/etat.2023.00149 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-06-29 06:57:48 [Bib_Time] => 2023-06-29 06:57:48 [KeysWordContens] => Glucose metabolism reprogramming promotes immune escape of hepatocellular carcinoma cells, Hepatocellular carcinoma, reprogramming of glucose metabolism, immune escape, Hepatocellular carcinoma (HCC) is a complex process that plays an important role in its progression. Abnormal glucose metabolism in HCC cells can meet the nutrients required for the occurrence and development of liver cancer, better adapt to changes in the surrounding microenvironment, and escape the attack of the immune system on the tumor. There is a close relationship between reprogramming of glucose metabolism and immune escape. This article reviews the current status and progress of glucose metabolism reprogramming in promoting immune escape in liver cancer, aiming to provide new strategies for clinical immunotherapy of liver cancer. ,Qiuyue Zhang ... Mengsen Li [PublishedText] => Published [IsEdit] => 0 [AccountId] => 38 [Zh] => 1 ) [151] => Array ( [ArticleId] => 639 [Create_Time] => 2023-07-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202307/20230701023018.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002150/1002150.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002150/1002150.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002150/1002150_cover.png [JournalsId] => 4 [Title] => An introductory review of post-resection chemotherapeutics for primary brain tumors [Abstract] => The treatment of central nervous system (CNS) tumors is complicated by high rates of recurrence and treatment resistance that contribute to high morbidity and mortality (Nat Rev Neurol. 2022;18:221 [AbstractComplete] =>The treatment of central nervous system (CNS) tumors is complicated by high rates of recurrence and treatment resistance that contribute to high morbidity and mortality (Nat Rev Neurol. 2022;18:221–36. doi: 10.1038/s41582-022-00621-0). One of the challenges of treating these tumors is the limited permeability of the blood brain barrier (BBB). Early pharmacologic treatments worked to overcome the BBB by targeting vulnerabilities in the tumor cell replication process directly through alkylating agents like temozolomide. However, as advancements have been made options have expanded to include immunologic targets through the use of monoclonal antibodies. In the future, treatment will likely continue to focus on the use of immunotherapies, as well as emerging technology like the use of low-intensity focused ultrasound (LIFU). Ultimately, this paper serves as an introductory overview of current therapeutic options for post-resection primary brain tumors, as well as a look towards future work and emerging treatment options.
[Names] => Meaghan McGovern ... Brandon Lucke-Wold [Doi] => 10.37349/etat.2023.00150 [Published] => June 30, 2023 [Viewed] => 805 [Downloaded] => 33 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00150 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:537–544 [Recommend] => 0 [Keywords] => Chemotherapeutics, primary central nervous system tumor, blood brain barrier [DetailTitle] => [DetailUrl] => [Id] => 1002150 [ris] => https://www.explorationpub.com/uploads/Article/A1002150/61fd7ad78170b73cd985e1847f9104f3.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002150/23550ec2f7f0318791a56b6696dcade8.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => McGovern M, Scanlon M, Stanton A, Lucke-Wold B. An introductory review of post-resection chemotherapeutics for primary brain tumors. Explor Target Antitumor Ther. 2023;4:537–44. https://doi.org/10.37349/etat.2023.00150 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-06-29 07:50:34 [Bib_Time] => 2023-06-29 07:50:34 [KeysWordContens] => An introductory review of post-resection chemotherapeutics for primary brain tumors, Chemotherapeutics, primary central nervous system tumor, blood brain barrier, The treatment of central nervous system (CNS) tumors is complicated by high rates of recurrence and treatment resistance that contribute to high morbidity and mortality (Nat Rev Neurol. 2022;18:221–36. doi: 10.1038/s41582-022-00621-0). One of the challenges of treating these tumors is the limited permeability of the blood brain barrier (BBB). Early pharmacologic treatments worked to overcome the BBB by targeting vulnerabilities in the tumor cell replication process directly through alkylating agents like temozolomide. However, as advancements have been made options have expanded to include immunologic targets through the use of monoclonal antibodies. In the future, treatment will likely continue to focus on the use of immunotherapies, as well as emerging technology like the use of low-intensity focused ultrasound (LIFU). Ultimately, this paper serves as an introductory overview of current therapeutic options for post-resection primary brain tumors, as well as a look towards future work and emerging treatment options. ,Meaghan McGovern ... Brandon Lucke-Wold [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [152] => Array ( [ArticleId] => 661 [Create_Time] => 2023-07-19 [zipUrl] => https://www.explorationpub.com/uploads/zip/202309/20230901014445.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002151/1002151.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002151/1002151.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002151/1002151_cover.png [JournalsId] => 4 [Title] => Current role of machine learning and radiogenomics in precision neuro-oncology [Abstract] => In the past few years, artificial intelligence (AI) has been increasingly used to create tools that can enhance workflow in medicine. In particular, neuro-oncology has benefited from the use of AI a [AbstractComplete] =>In the past few years, artificial intelligence (AI) has been increasingly used to create tools that can enhance workflow in medicine. In particular, neuro-oncology has benefited from the use of AI and especially machine learning (ML) and radiogenomics, which are subfields of AI. ML can be used to develop algorithms that dynamically learn from available medical data in order to automatically do specific tasks. On the other hand, radiogenomics can identify relationships between tumor genetics and imaging features, thus possibly giving new insights into the pathophysiology of tumors. Therefore, ML and radiogenomics could help treatment tailoring, which is crucial in personalized neuro-oncology. The aim of this review is to illustrate current and possible future applications of ML and radiomics in neuro-oncology.
[Names] => Teresa Perillo ... Andrea Manto [Doi] => 10.37349/etat.2023.00151 [Published] => July 19, 2023 [Viewed] => 733 [Downloaded] => 36 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00151 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 88 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:545–555 [Recommend] => 0 [Keywords] => Artificial intelligence, machine learning, radiogenomics, neuro-oncology, glioblastoma, meningioma [DetailTitle] => Artificial Intelligence for Precision Oncology [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/88 [Id] => 1002151 [ris] => https://www.explorationpub.com/uploads/Article/A1002151/5effdcbd5f84dc2f4c4d94b2ec023898.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002151/3f5114d34bb0db4a5fe4d9cdd5954f9d.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Perillo T, de Giorgi M, Papace UM, Serino A, Cuocolo R, Manto A. Current role of machine learning and radiogenomics in precision neuro-oncology. Explor Target Antitumor Ther. 2023;4:545–55. https://doi.org/10.37349/etat.2023.00151 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-07-14 05:41:29 [Bib_Time] => 2023-07-14 05:41:29 [KeysWordContens] => Current role of machine learning and radiogenomics in precision neuro-oncology, Artificial intelligence, machine learning, radiogenomics, neuro-oncology, glioblastoma, meningioma, In the past few years, artificial intelligence (AI) has been increasingly used to create tools that can enhance workflow in medicine. In particular, neuro-oncology has benefited from the use of AI and especially machine learning (ML) and radiogenomics, which are subfields of AI. ML can be used to develop algorithms that dynamically learn from available medical data in order to automatically do specific tasks. On the other hand, radiogenomics can identify relationships between tumor genetics and imaging features, thus possibly giving new insights into the pathophysiology of tumors. Therefore, ML and radiogenomics could help treatment tailoring, which is crucial in personalized neuro-oncology. The aim of this review is to illustrate current and possible future applications of ML and radiomics in neuro-oncology. ,Teresa Perillo ... Andrea Manto [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [153] => Array ( [ArticleId] => 673 [Create_Time] => 2023-08-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202308/20230824055857.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002152/1002152.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002152/1002152.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002152/1002152_cover.png [JournalsId] => 4 [Title] => Potential tactics with certain gut microbiota for the treatment of unresectable hepatocellular carcinoma [Abstract] => Hepatocellular carcinoma (HCC) constitutes an extremely malignant form of primary liver cancer. Intricate connections linking to the immune system might be associated with the pathogenesis of HCC. M [AbstractComplete] =>Hepatocellular carcinoma (HCC) constitutes an extremely malignant form of primary liver cancer. Intricate connections linking to the immune system might be associated with the pathogenesis of HCC. Meanwhile, immunotherapy with immune checkpoint inhibitors has been established to be a favorable therapeutic possibility for advanced HCC. Although curative opportunities for advanced HCC are restricted, the immune checkpoint immunotherapy has developed as the main choice for treating HCC. However, patients with metabolic-associated fatty liver disease (MAFLD)-linked HCC might be less likely to benefit from the immunotherapy alone. The limitation of the effect of the immunotherapy might be owing to the impaired T cell activation in MAFLD patients, which could be well explained by a dysfunctional gut-liver axis. Gut microbiota and their metabolites including several bile acids could contribute to modulating the responses of the immune checkpoint immunotherapy. Roles of gut microbiota in the development of cancers have expected great interest in the latest studies. Here, an interplay between the gut and liver has been presented, which might suggest to affect the efficacy of immune checkpoint immunotherapy against HCC.
[Names] => Sayuri Yoshikawa ... Satoru Matsuda [Doi] => 10.37349/etat.2023.00152 [Published] => August 24, 2023 [Viewed] => 1638 [Downloaded] => 674 [Subject] => Perspective [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00152 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 70 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:556–568 [Recommend] => 0 [Keywords] => Hepatocellular carcinoma, non-alcoholic fatty liver disease, metabolic-associated fatty liver disease, gut microbiota, probiotics, immune checkpoint inhibitors, T helper 17 cells, regulatory T cells [DetailTitle] => Cancer Immunotherapy and Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/70 [Id] => 1002152 [ris] => https://www.explorationpub.com/uploads/Article/A1002152/8575347c101660b3678804d539c78f63.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002152/f76c4a3df3bcf30344849dde7c3c8343.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Yoshikawa S, Taniguchi K, Sawamura H, Ikeda Y, Asai T, Tsuji A, et al. Potential tactics with certain gut microbiota for the treatment of unresectable hepatocellular carcinoma. Explor Target Antitumor Ther. 2023;4:556–68. https://doi.org/10.37349/etat.2023.00152 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-08-24 05:58:57 [Bib_Time] => 2023-08-24 05:58:57 [KeysWordContens] => Potential tactics with certain gut microbiota for the treatment of unresectable hepatocellular carcinoma, Hepatocellular carcinoma, non-alcoholic fatty liver disease, metabolic-associated fatty liver disease, gut microbiota, probiotics, immune checkpoint inhibitors, T helper 17 cells, regulatory T cells, Hepatocellular carcinoma (HCC) constitutes an extremely malignant form of primary liver cancer. Intricate connections linking to the immune system might be associated with the pathogenesis of HCC. Meanwhile, immunotherapy with immune checkpoint inhibitors has been established to be a favorable therapeutic possibility for advanced HCC. Although curative opportunities for advanced HCC are restricted, the immune checkpoint immunotherapy has developed as the main choice for treating HCC. However, patients with metabolic-associated fatty liver disease (MAFLD)-linked HCC might be less likely to benefit from the immunotherapy alone. The limitation of the effect of the immunotherapy might be owing to the impaired T cell activation in MAFLD patients, which could be well explained by a dysfunctional gut-liver axis. Gut microbiota and their metabolites including several bile acids could contribute to modulating the responses of the immune checkpoint immunotherapy. Roles of gut microbiota in the development of cancers have expected great interest in the latest studies. Here, an interplay between the gut and liver has been presented, which might suggest to affect the efficacy of immune checkpoint immunotherapy against HCC. ,Sayuri Yoshikawa ... Satoru Matsuda [PublishedText] => Published [IsEdit] => 0 [AccountId] => 77 [Zh] => 1 ) [154] => Array ( [ArticleId] => 674 [Create_Time] => 2023-08-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202308/20230828050147.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002153/1002153.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002153/1002153.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002153/1002153_cover.png [JournalsId] => 4 [Title] => Emerging role of quantitative imaging (radiomics) and artificial intelligence in precision oncology [Abstract] => Cancer is a fatal disease and the second most cause of death worldwide. Treatment of cancer is a complex process and requires a multi-modality-based approach. Cancer detection and treatment starts w [AbstractComplete] =>Cancer is a fatal disease and the second most cause of death worldwide. Treatment of cancer is a complex process and requires a multi-modality-based approach. Cancer detection and treatment starts with screening/diagnosis and continues till the patient is alive. Screening/diagnosis of the disease is the beginning of cancer management and continued with the staging of the disease, planning and delivery of treatment, treatment monitoring, and ongoing monitoring and follow-up. Imaging plays an important role in all stages of cancer management. Conventional oncology practice considers that all patients are similar in a disease type, whereas biomarkers subgroup the patients in a disease type which leads to the development of precision oncology. The utilization of the radiomic process has facilitated the advancement of diverse imaging biomarkers that find application in precision oncology. The role of imaging biomarkers and artificial intelligence (AI) in oncology has been investigated by many researchers in the past. The existing literature is suggestive of the increasing role of imaging biomarkers and AI in oncology. However, the stability of radiomic features has also been questioned. The radiomic community has recognized that the instability of radiomic features poses a danger to the global generalization of radiomic-based prediction models. In order to establish radiomic-based imaging biomarkers in oncology, the robustness of radiomic features needs to be established on a priority basis. This is because radiomic models developed in one institution frequently perform poorly in other institutions, most likely due to radiomic feature instability. To generalize radiomic-based prediction models in oncology, a number of initiatives, including Quantitative Imaging Network (QIN), Quantitative Imaging Biomarkers Alliance (QIBA), and Image Biomarker Standardisation Initiative (IBSI), have been launched to stabilize the radiomic features.
[Names] => Ashish Kumar Jha ... Andre Dekker [Doi] => 10.37349/etat.2023.00153 [Published] => August 24, 2023 [Viewed] => 912 [Downloaded] => 20 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00153 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 88 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:569–582 [Recommend] => 0 [Keywords] => Precision oncology, radiomics, imaging biomarkers, artificial intelligence [DetailTitle] => Artificial Intelligence for Precision Oncology [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/88 [Id] => 1002153 [ris] => https://www.explorationpub.com/uploads/Article/A1002153/ec1f4ee64c9f2b7dcee1269d8ea8c234.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002153/731cdde56d44fac3054cf819d91a0d0f.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-27 [CitethisArticle] => Jha AK, Mithun S, Sherkhane UB, Dwivedi P, Puts S, Osong B, et al. Emerging role of quantitative imaging (radiomics) and artificial intelligence in precision oncology. Explor Target Antitumor Ther. 2023;4:569–82. https://doi.org/10.37349/etat.2023.00153 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-08-28 05:01:48 [Bib_Time] => 2023-08-28 05:01:48 [KeysWordContens] => Emerging role of quantitative imaging (radiomics) and artificial intelligence in precision oncology, Precision oncology, radiomics, imaging biomarkers, artificial intelligence, Cancer is a fatal disease and the second most cause of death worldwide. Treatment of cancer is a complex process and requires a multi-modality-based approach. Cancer detection and treatment starts with screening/diagnosis and continues till the patient is alive. Screening/diagnosis of the disease is the beginning of cancer management and continued with the staging of the disease, planning and delivery of treatment, treatment monitoring, and ongoing monitoring and follow-up. Imaging plays an important role in all stages of cancer management. Conventional oncology practice considers that all patients are similar in a disease type, whereas biomarkers subgroup the patients in a disease type which leads to the development of precision oncology. The utilization of the radiomic process has facilitated the advancement of diverse imaging biomarkers that find application in precision oncology. The role of imaging biomarkers and artificial intelligence (AI) in oncology has been investigated by many researchers in the past. The existing literature is suggestive of the increasing role of imaging biomarkers and AI in oncology. However, the stability of radiomic features has also been questioned. The radiomic community has recognized that the instability of radiomic features poses a danger to the global generalization of radiomic-based prediction models. In order to establish radiomic-based imaging biomarkers in oncology, the robustness of radiomic features needs to be established on a priority basis. This is because radiomic models developed in one institution frequently perform poorly in other institutions, most likely due to radiomic feature instability. To generalize radiomic-based prediction models in oncology, a number of initiatives, including Quantitative Imaging Network (QIN), Quantitative Imaging Biomarkers Alliance (QIBA), and Image Biomarker Standardisation Initiative (IBSI), have been launched to stabilize the radiomic features. ,Ashish Kumar Jha ... Andre Dekker [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [155] => Array ( [ArticleId] => 678 [Create_Time] => 2023-08-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202308/20230825012144.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002154/1002154.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002154/1002154.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002154/1002154_cover.png [JournalsId] => 4 [Title] => B-cell lymphoma 2 family members and sarcomas: a promising target in a heterogeneous disease [Abstract] => Targeting the B-cell lymphoma 2 (Bcl-2) family proteins has been the backbone for hematological malignancies with overall survival improvements. The Bcl-2 family is a major player in apoptosis regul [AbstractComplete] =>Targeting the B-cell lymphoma 2 (Bcl-2) family proteins has been the backbone for hematological malignancies with overall survival improvements. The Bcl-2 family is a major player in apoptosis regulation and, has captured the researcher’s interest in the treatment of solid tumors. Sarcomas are a heterogeneous group of diseases, comprising several entities, with high morbidity and mortality and with few specific therapies available. The treatment for sarcomas is based on platinum regimens, with variable results and poor outcomes, especially in advanced lesions. The high number of different sarcoma entities makes treatment standardization as well as the performance of clinical trials difficult. The use of Bcl-2 family members modifiers has revealed promising results in in vitro and in vivo models and may be a valid option, especially when used in combination with chemotherapy. In this article, a revision of these results and possibilities for the use of Bcl-2 family members inhibitors in sarcomas was performed.
[Names] => Rui Caetano Oliveira ... José Casanova [Doi] => 10.37349/etat.2023.00154 [Published] => August 24, 2023 [Viewed] => 495 [Downloaded] => 24 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00154 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 52 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:583–599 [Recommend] => 0 [Keywords] => B-cell lymphoma 2, sarcomas, therapy [DetailTitle] => The Role of Bcl-2 Family Proteins in Cancer Progression and Their Relevance to Cancer Therapy [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/52 [Id] => 1002154 [ris] => https://www.explorationpub.com/uploads/Article/A1002154/fa328b6b14b4603c0fb6ead726242a42.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002154/10f8827a037e686785898002325e37a4.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Oliveira RC, Gama J, Casanova J. B-cell lymphoma 2 family members and sarcomas: a promising target in a heterogeneous disease. Explor Target Antitumor Ther. 2023;4:583–99. https://doi.org/10.37349/etat.2023.00154 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-08-16 02:25:42 [Bib_Time] => 2023-08-16 02:25:42 [KeysWordContens] => B-cell lymphoma 2 family members and sarcomas: a promising target in a heterogeneous disease, B-cell lymphoma 2, sarcomas, therapy, Targeting the B-cell lymphoma 2 (Bcl-2) family proteins has been the backbone for hematological malignancies with overall survival improvements. The Bcl-2 family is a major player in apoptosis regulation and, has captured the researcher’s interest in the treatment of solid tumors. Sarcomas are a heterogeneous group of diseases, comprising several entities, with high morbidity and mortality and with few specific therapies available. The treatment for sarcomas is based on platinum regimens, with variable results and poor outcomes, especially in advanced lesions. The high number of different sarcoma entities makes treatment standardization as well as the performance of clinical trials difficult. The use of Bcl-2 family members modifiers has revealed promising results in in vitro and in vivo models and may be a valid option, especially when used in combination with chemotherapy. In this article, a revision of these results and possibilities for the use of Bcl-2 family members inhibitors in sarcomas was performed. ,Rui Caetano Oliveira ... José Casanova [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [156] => Array ( [ArticleId] => 679 [Create_Time] => 2023-08-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202309/20230901020326.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002155/1002155.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002155/1002155.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002155/1002155_cover.png [JournalsId] => 4 [Title] => Aspirin and the metabolic hallmark of cancer: novel therapeutic opportunities for colorectal cancer [Abstract] => Aspirin is a well-known nonsteroidal anti-inflammatory drug (NSAID) that has a recognized role in cancer prevention as well as evidence to support its use as an adjuvant for cancer treatment. Import [AbstractComplete] =>Aspirin is a well-known nonsteroidal anti-inflammatory drug (NSAID) that has a recognized role in cancer prevention as well as evidence to support its use as an adjuvant for cancer treatment. Importantly there has been an increasing number of studies contributing to the mechanistic understanding of aspirins’ anti-tumour effects and these studies continue to inform the potential clinical use of aspirin for both the prevention and treatment of cancer. This review focuses on the emerging role of aspirin as a regulator of metabolic reprogramming, an essential “hallmark of cancer” required to support the increased demand for biosynthetic intermediates needed for sustained proliferation. Cancer cells frequently undergo metabolic rewiring driven by oncogenic pathways such as hypoxia-inducible factor (HIF), wingless-related integration site (Wnt), mammalian target of rapamycin (mTOR), and nuclear factor kappa light chain enhancer of activated B cells (NF-κB), which supports the increased proliferative rate as tumours develop and progress. Reviewed here, cellular metabolic reprogramming has been identified as a key mechanism of action of aspirin and include the regulation of key metabolic drivers, the regulation of enzymes involved in glycolysis and glutaminolysis, and altered nutrient utilisation upon aspirin exposure. Importantly, as aspirin treatment exposes metabolic vulnerabilities in tumour cells, there is an opportunity for the use of aspirin in combination with specific metabolic inhibitors in particular, glutaminase (GLS) inhibitors currently in clinical trials such as telaglenastat (CB-839) and IACS-6274 for the treatment of colorectal and potentially other cancers. The increasing evidence that aspirin impacts metabolism in cancer cells suggests that aspirin could provide a simple, relatively safe, and cost-effective way to target this important hallmark of cancer. Excitingly, this review highlights a potential new role for aspirin in improving the efficacy of a new generation of metabolic inhibitors currently undergoing clinical investigation.
[Names] => Ashley J. Hoskin ... Emma E. Vincent [Doi] => 10.37349/etat.2023.00155 [Published] => August 28, 2023 [Viewed] => 834 [Downloaded] => 23 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00155 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:600–615 [Recommend] => 0 [Keywords] => Aspirin, cancer metabolism, metabolic hallmark, colorectal cancer, cancer prevention, nonsteroidal anti-inflammatory drugs, adjuvant for therapy, anti-tumour [DetailTitle] => [DetailUrl] => [Id] => 1002155 [ris] => https://www.explorationpub.com/uploads/Article/A1002155/fbdc880f3ce9f48037ff01638dab02bd.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002155/d35a1e9ae9b5288be1b298bed2d830d8.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Hoskin AJ, Holt AK, Legge DN, Collard TJ, Williams AC, Vincent EE. Aspirin and the metabolic hallmark of cancer: novel therapeutic opportunities for colorectal cancer. Explor Target Antitumor Ther. 2023;4:600–15. https://doi.org/10.37349/etat.2023.00155 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-08-16 02:50:49 [Bib_Time] => 2023-08-16 02:50:49 [KeysWordContens] => Aspirin and the metabolic hallmark of cancer: novel therapeutic opportunities for colorectal cancer, Aspirin, cancer metabolism, metabolic hallmark, colorectal cancer, cancer prevention, nonsteroidal anti-inflammatory drugs, adjuvant for therapy, anti-tumour, Aspirin is a well-known nonsteroidal anti-inflammatory drug (NSAID) that has a recognized role in cancer prevention as well as evidence to support its use as an adjuvant for cancer treatment. Importantly there has been an increasing number of studies contributing to the mechanistic understanding of aspirins’ anti-tumour effects and these studies continue to inform the potential clinical use of aspirin for both the prevention and treatment of cancer. This review focuses on the emerging role of aspirin as a regulator of metabolic reprogramming, an essential “hallmark of cancer” required to support the increased demand for biosynthetic intermediates needed for sustained proliferation. Cancer cells frequently undergo metabolic rewiring driven by oncogenic pathways such as hypoxia-inducible factor (HIF), wingless-related integration site (Wnt), mammalian target of rapamycin (mTOR), and nuclear factor kappa light chain enhancer of activated B cells (NF-κB), which supports the increased proliferative rate as tumours develop and progress. Reviewed here, cellular metabolic reprogramming has been identified as a key mechanism of action of aspirin and include the regulation of key metabolic drivers, the regulation of enzymes involved in glycolysis and glutaminolysis, and altered nutrient utilisation upon aspirin exposure. Importantly, as aspirin treatment exposes metabolic vulnerabilities in tumour cells, there is an opportunity for the use of aspirin in combination with specific metabolic inhibitors in particular, glutaminase (GLS) inhibitors currently in clinical trials such as telaglenastat (CB-839) and IACS-6274 for the treatment of colorectal and potentially other cancers. The increasing evidence that aspirin impacts metabolism in cancer cells suggests that aspirin could provide a simple, relatively safe, and cost-effective way to target this important hallmark of cancer. Excitingly, this review highlights a potential new role for aspirin in improving the efficacy of a new generation of metabolic inhibitors currently undergoing clinical investigation. ,Ashley J. Hoskin ... Emma E. Vincent [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [157] => Array ( [ArticleId] => 681 [Create_Time] => 2023-08-30 [zipUrl] => https://www.explorationpub.com/uploads/zip/202308/20230830011126.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002156/1002156.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002156/1002156.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002156/1002156_cover.png [JournalsId] => 4 [Title] => Nuclear epidermal growth factor receptor as a therapeutic target [Abstract] => Epidermal growth factor receptor (EGFR) is one of the most well-studied oncogenes with roles in proliferation, growth, metastasis, and therapeutic resistance. This intense study has led to the devel [AbstractComplete] =>Epidermal growth factor receptor (EGFR) is one of the most well-studied oncogenes with roles in proliferation, growth, metastasis, and therapeutic resistance. This intense study has led to the development of a range of targeted therapeutics including small-molecule tyrosine kinase inhibitors (TKIs), monoclonal antibodies, and nanobodies. These drugs are excellent at blocking the activation and kinase function of wild-type EGFR (wtEGFR) and several common EGFR mutants. These drugs have significantly improved outcomes for patients with cancers including head and neck, glioblastoma, colorectal, and non-small cell lung cancer (NSCLC). However, therapeutic resistance is often seen, resulting from acquired mutations or activation of compensatory signaling pathways. Additionally, these therapies are ineffective in tumors where EGFR is found predominantly in the nucleus, as can be found in triple negative breast cancer (TNBC). In TNBC, EGFR is subjected to alternative trafficking which drives the nuclear localization of the receptor. In the nucleus, EGFR interacts with several proteins to activate transcription, DNA repair, migration, and chemoresistance. Nuclear EGFR (nEGFR) correlates with metastatic disease and worse patient prognosis yet targeting its nuclear localization has proved difficult. This review provides an overview of current EGFR-targeted therapies and novel peptide-based therapies that block nEGFR, as well as their clinical applications and potential for use in oncology.
[Names] => Benjamin Atwell ... Joyce Schroeder [Doi] => 10.37349/etat.2023.00156 [Published] => August 30, 2023 [Viewed] => 672 [Downloaded] => 21 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00156 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 137 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:616–629 [Recommend] => 0 [Keywords] => Triple negative breast cancer, epidermal growth factor, mucin-1, retrotranslocation [DetailTitle] => Innovative Strategies to Target Triple-negative Breast Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/137 [Id] => 1002156 [ris] => https://www.explorationpub.com/uploads/Article/A1002156/a0673e6ebe20bd9aceec6454aba3d11e.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002156/dc4dc59d02d819125c752bb1c4eb0703.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Atwell B, Chalasani P, Schroeder J. Nuclear epidermal growth factor receptor as a therapeutic target. Explor Target Antitumor Ther. 2023;4:616–29. https://doi.org/10.37349/etat.2023.00156 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-08-16 03:46:49 [Bib_Time] => 2023-08-16 03:46:49 [KeysWordContens] => Nuclear epidermal growth factor receptor as a therapeutic target, Triple negative breast cancer, epidermal growth factor, mucin-1, retrotranslocation, Epidermal growth factor receptor (EGFR) is one of the most well-studied oncogenes with roles in proliferation, growth, metastasis, and therapeutic resistance. This intense study has led to the development of a range of targeted therapeutics including small-molecule tyrosine kinase inhibitors (TKIs), monoclonal antibodies, and nanobodies. These drugs are excellent at blocking the activation and kinase function of wild-type EGFR (wtEGFR) and several common EGFR mutants. These drugs have significantly improved outcomes for patients with cancers including head and neck, glioblastoma, colorectal, and non-small cell lung cancer (NSCLC). However, therapeutic resistance is often seen, resulting from acquired mutations or activation of compensatory signaling pathways. Additionally, these therapies are ineffective in tumors where EGFR is found predominantly in the nucleus, as can be found in triple negative breast cancer (TNBC). In TNBC, EGFR is subjected to alternative trafficking which drives the nuclear localization of the receptor. In the nucleus, EGFR interacts with several proteins to activate transcription, DNA repair, migration, and chemoresistance. Nuclear EGFR (nEGFR) correlates with metastatic disease and worse patient prognosis yet targeting its nuclear localization has proved difficult. This review provides an overview of current EGFR-targeted therapies and novel peptide-based therapies that block nEGFR, as well as their clinical applications and potential for use in oncology. ,Benjamin Atwell ... Joyce Schroeder [PublishedText] => Published [IsEdit] => 0 [AccountId] => 57 [Zh] => 1 ) [158] => Array ( [ArticleId] => 683 [Create_Time] => 2023-08-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202309/20230901020914.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002157/1002157.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002157/1002157.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002157/1002157_cover.png [JournalsId] => 4 [Title] => Nanomedicine strategies to counteract cancer stemness and chemoresistance [Abstract] => Cancer stem-like cells (CSCs) identified by self-renewal ability and tumor-initiating potential are responsible for tumor recurrence and metastasis in many cancers. Conventional chemotherapy fails t [AbstractComplete] =>Cancer stem-like cells (CSCs) identified by self-renewal ability and tumor-initiating potential are responsible for tumor recurrence and metastasis in many cancers. Conventional chemotherapy fails to eradicate CSCs that hold a state of dormancy and possess multi-drug resistance. Spurred by the progress of nanotechnology for drug delivery and biomedical applications, nanomedicine has been increasingly developed to tackle stemness-associated chemotherapeutic resistance for cancer therapy. This review focuses on advances in nanomedicine-mediated therapeutic strategies to overcome chemoresistance by specifically targeting CSCs, the combination of chemotherapeutics with chemopotentiators, and programmable controlled drug release. Perspectives from materials and formulations at the nano-scales are specifically surveyed. Future opportunities and challenges are also discussed.
[Names] => Huayu Liu ... Ran Mo [Doi] => 10.37349/etat.2023.00157 [Published] => August 30, 2023 [Viewed] => 548 [Downloaded] => 21 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00157 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:630–656 [Recommend] => 0 [Keywords] => Drug delivery, nanomedicine, chemoresistance, cancer stem-like cells, cancer therapy [DetailTitle] => [DetailUrl] => [Id] => 1002157 [ris] => https://www.explorationpub.com/uploads/Article/A1002157/d08cbe19a5b7fa2620114f5d3248c94f.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002157/486e238583c7db0983310969e6b278d0.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Liu H, Liu M, Zhao Y, Mo R. Nanomedicine strategies to counteract cancer stemness and chemoresistance. Explor Target Antitumor Ther. 2023;4:630–56. https://doi.org/10.37349/etat.2023.00157 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-08-28 06:01:47 [Bib_Time] => 2023-08-28 06:01:47 [KeysWordContens] => Nanomedicine strategies to counteract cancer stemness and chemoresistance, Drug delivery, nanomedicine, chemoresistance, cancer stem-like cells, cancer therapy, Cancer stem-like cells (CSCs) identified by self-renewal ability and tumor-initiating potential are responsible for tumor recurrence and metastasis in many cancers. Conventional chemotherapy fails to eradicate CSCs that hold a state of dormancy and possess multi-drug resistance. Spurred by the progress of nanotechnology for drug delivery and biomedical applications, nanomedicine has been increasingly developed to tackle stemness-associated chemotherapeutic resistance for cancer therapy. This review focuses on advances in nanomedicine-mediated therapeutic strategies to overcome chemoresistance by specifically targeting CSCs, the combination of chemotherapeutics with chemopotentiators, and programmable controlled drug release. Perspectives from materials and formulations at the nano-scales are specifically surveyed. Future opportunities and challenges are also discussed. ,Huayu Liu ... Ran Mo [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [159] => Array ( [ArticleId] => 700 [Create_Time] => 2023-08-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202309/20230901022441.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002158/1002158.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002158/1002158.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002158/1002158_cover.png [JournalsId] => 4 [Title] => Deep learning based automated epidermal growth factor receptor and anaplastic lymphoma kinase status prediction of brain metastasis in non-small cell lung cancer [Abstract] => Aim: The aim of this study was to investigate the feasibility of developing a deep learning (DL) algorithm for classifying brain metastases from non-small cell lung cancer (NSCLC) into epidermal [AbstractComplete] =>The aim of this study was to investigate the feasibility of developing a deep learning (DL) algorithm for classifying brain metastases from non-small cell lung cancer (NSCLC) into epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement groups and to compare the accuracy with classification based on semantic features on imaging.
Data set of 117 patients was analysed from 2014 to 2018 out of which 33 patients were EGFR positive, 43 patients were ALK positive and 41 patients were negative for either mutation. Convolutional neural network (CNN) architecture efficient net was used to study the accuracy of classification using T1 weighted (T1W) magnetic resonance imaging (MRI) sequence, T2 weighted (T2W) MRI sequence, T1W post contrast (T1post) MRI sequence, fluid attenuated inversion recovery (FLAIR) MRI sequences. The dataset was divided into 80% training and 20% testing. The associations between mutation status and semantic features, specifically sex, smoking history, EGFR mutation and ALK rearrangement status, extracranial metastasis, performance status and imaging variables of brain metastasis were analysed using descriptive analysis [chi-square test (χ2)], univariate and multivariate logistic regression analysis assuming 95% confidence interval (CI).
In this study of 117 patients, the analysis by semantic method showed 79.2% of the patients belonged to ALK positive were non-smokers as compared to double negative groups (P = 0.03). There was a 10-fold increase in ALK positivity as compared to EGFR positivity in ring enhancing lesions patients (P = 0.015) and there was also a 6.4-fold increase in ALK positivity as compared to double negative groups in meningeal involvement patients (P = 0.004). Using CNN Efficient Net DL model, the study achieved 76% accuracy in classifying ALK rearrangement and EGFR mutations without manual segmentation of metastatic lesions. Analysis of the manually segmented dataset resulted in improved accuracy of 89% through this model.
Both semantic features and DL model showed comparable accuracy in classifying EGFR mutation and ALK rearrangement. Both methods can be clinically used to predict mutation status while biopsy or genetic testing is undertaken.
Early diagnosis of paediatric brain tumors significantly improves the outcome. The aim is to study magnetic resonance imaging (MRI) features of paediatric brain tumors and to develop an automated segmentation (AS) tool which could segment and classify tumors using deep learning methods and compare with radiologist assessment.
This study included 94 cases, of which 75 were diagnosed cases of ependymoma, medulloblastoma, brainstem glioma, and pilocytic astrocytoma and 19 were normal MRI brain cases. The data was randomized into training data, 64 cases; test data, 21 cases and validation data, 9 cases to devise a deep learning algorithm to segment the paediatric brain tumor. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the deep learning model were compared with radiologist’s findings. Performance evaluation of AS was done based on Dice score and Hausdorff95 distance.
Analysis of MRI semantic features was done with necrosis and haemorrhage as predicting features for ependymoma, diffusion restriction and cystic changes were predictors for medulloblastoma. The accuracy of detecting abnormalities was 90%, with a specificity of 100%. Further segmentation of the tumor into enhancing and non-enhancing components was done. The segmentation results for whole tumor (WT), enhancing tumor (ET), and non-enhancing tumor (NET) have been analyzed by Dice score and Hausdorff95 distance. The accuracy of prediction of all MRI features was compared with experienced radiologist’s findings. Substantial agreement observed between the classification by model and the radiologist’s given classification [K-0.695 (K is Cohen’s kappa score for interrater reliability)].
The deep learning model had very high accuracy and specificity for predicting the magnetic resonance (MR) characteristics and close to 80% accuracy in predicting tumor type. This model can serve as a potential tool to make a timely and accurate diagnosis for radiologists not trained in neuroradiology.
Precision oncology is a rapidly evolving field that uses advanced technologies to deliver personalized cancer care based on a patient’s unique genetic and clinical profile. The use of artificial intelligence (AI) in precision oncology has shown great potential to improve diagnosis, treatment planning, and treatment outcomes. However, the integration of AI in precision oncology also raises important ethical considerations related to patient privacy, autonomy, and protection from bias. In this opinion paper, an overview is provided of previous studies that have explored the use of AI in precision oncology and the ethical considerations associated with this technology. The conclusions of these studies are compared, and the importance of approaching the use of AI in precision oncology with caution is emphasized. It is stressed that patient privacy, autonomy, and protection from bias should be made central to the development and use of AI in precision oncology. Clear guidelines and regulations must be established to ensure that AI is used ethically and for the benefit of patients. The use of AI in precision oncology has the potential to revolutionize cancer care, but it should be ensured that it striked a balance between advancements in technology and ethical considerations. In conclusion, the use of AI in precision oncology is a promising development that has the potential to improve cancer outcomes. However, ethical considerations related to patient privacy, autonomy, and protection from bias must be central to the development and use of AI in precision oncology.
[Names] => Bahareh Farasati Far [Doi] => 10.37349/etat.2023.00160 [Published] => August 31, 2023 [Viewed] => 644 [Downloaded] => 23 [Subject] => Perspective [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00160 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 88 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:685–689 [Recommend] => 0 [Keywords] => Artificial intelligence, precision oncology, ethics, patient privacy, patient autonomy, machine learning, personalized medicine, data protection [DetailTitle] => Artificial Intelligence for Precision Oncology [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/88 [Id] => 1002160 [ris] => https://www.explorationpub.com/uploads/Article/A1002160/a74001540fab44f84fd84ad0d2cf09ee.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002160/980d9516a3397a18620803cc8f57d400.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-27 [CitethisArticle] => Farasati Far B. Artificial intelligence ethics in precision oncology: balancing advancements in technology with patient privacy and autonomy. Explor Target Antitumor Ther. 2023;4:685–9. https://doi.org/10.37349/etat.2023.00160 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-08-29 10:45:37 [Bib_Time] => 2023-08-29 10:45:37 [KeysWordContens] => Artificial intelligence ethics in precision oncology: balancing advancements in technology with patient privacy and autonomy, Artificial intelligence, precision oncology, ethics, patient privacy, patient autonomy, machine learning, personalized medicine, data protection, Precision oncology is a rapidly evolving field that uses advanced technologies to deliver personalized cancer care based on a patient’s unique genetic and clinical profile. The use of artificial intelligence (AI) in precision oncology has shown great potential to improve diagnosis, treatment planning, and treatment outcomes. However, the integration of AI in precision oncology also raises important ethical considerations related to patient privacy, autonomy, and protection from bias. In this opinion paper, an overview is provided of previous studies that have explored the use of AI in precision oncology and the ethical considerations associated with this technology. The conclusions of these studies are compared, and the importance of approaching the use of AI in precision oncology with caution is emphasized. It is stressed that patient privacy, autonomy, and protection from bias should be made central to the development and use of AI in precision oncology. Clear guidelines and regulations must be established to ensure that AI is used ethically and for the benefit of patients. The use of AI in precision oncology has the potential to revolutionize cancer care, but it should be ensured that it striked a balance between advancements in technology and ethical considerations. In conclusion, the use of AI in precision oncology is a promising development that has the potential to improve cancer outcomes. However, ethical considerations related to patient privacy, autonomy, and protection from bias must be central to the development and use of AI in precision oncology. ,Bahareh Farasati Far [PublishedText] => Published [IsEdit] => 0 [AccountId] => 77 [Zh] => 1 ) [162] => Array ( [ArticleId] => 728 [Create_Time] => 2023-08-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202308/20230831065242.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002161/1002161.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002161/1002161.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002161/1002161_cover.png [JournalsId] => 4 [Title] => Anticancer action of naturally occurring emodin for the controlling of cervical cancer [Abstract] => One of the major causes of death on the globe is cancer. The fourth most frequent malignancy in women worldwide is cervical cancer. Several cancer patients are remaining incurable due to the emergen [AbstractComplete] =>One of the major causes of death on the globe is cancer. The fourth most frequent malignancy in women worldwide is cervical cancer. Several cancer patients are remaining incurable due to the emergence of medication resistance, despite notable advances in cancer research over the previous few decades. The importance of natural sources as possible therapeutic candidates may be significant. Anthraquinones are one of the many chemical families of natural products, and they stand out for their wide range of structural variations, notable biological activity, and low toxicity. A natural substance called emodin, an anthraquinone derivative, is present in the roots and rhizomes of several plants. This substance has demonstrated antineoplastic, anti-inflammatory, antiangiogenic, and antiproliferative properties. It is also capable of preventing cancer spread and can reverse cancer cells’ multidrug resistance. Emodin, a broad-spectrum inhibitor of cancer cells, have anticancer properties in many different types of biological pathways. These molecular mechanisms in cancer cells include the suppression of cell growth and proliferation, deterioration of the cell cycle arrest, the start of apoptosis, antimetastasis, and antiangiogenic impact. Therefore, the aim of the present review summarised the antiproliferative and anticarcinogenic qualities of cervical cancer of emodin.
[Names] => Priyanka S. Lande ... Leena P. Joge [Doi] => 10.37349/etat.2023.00161 [Published] => August 31, 2023 [Viewed] => 665 [Downloaded] => 19 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00161 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 73 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:690–698 [Recommend] => 0 [Keywords] => Anticancer, emodin, anti-proliferative, anti-carcinogenic [DetailTitle] => Plant Extracts as an Infinite Resource for New Anticancer Agents [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/73 [Id] => 1002161 [ris] => https://www.explorationpub.com/uploads/Article/A1002161/68c56c6b2ad55f2e55507079d1b77755.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002161/9a6a1076c23a291e93079a7df6c3ee4b.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-27 [CitethisArticle] => Lande PS, Adhao VS, Ambhore JP, Gaikwad KP, Chandak CS, Joge LP. Anticancer action of naturally occurring emodin for the controlling of cervical cancer. Explor Target Antitumor Ther. 2023;4:690–8. https://doi.org/10.37349/etat.2023.00161 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-08-31 06:52:42 [Bib_Time] => 2023-08-31 06:52:42 [KeysWordContens] => Anticancer action of naturally occurring emodin for the controlling of cervical cancer, Anticancer, emodin, anti-proliferative, anti-carcinogenic, One of the major causes of death on the globe is cancer. The fourth most frequent malignancy in women worldwide is cervical cancer. Several cancer patients are remaining incurable due to the emergence of medication resistance, despite notable advances in cancer research over the previous few decades. The importance of natural sources as possible therapeutic candidates may be significant. Anthraquinones are one of the many chemical families of natural products, and they stand out for their wide range of structural variations, notable biological activity, and low toxicity. A natural substance called emodin, an anthraquinone derivative, is present in the roots and rhizomes of several plants. This substance has demonstrated antineoplastic, anti-inflammatory, antiangiogenic, and antiproliferative properties. It is also capable of preventing cancer spread and can reverse cancer cells’ multidrug resistance. Emodin, a broad-spectrum inhibitor of cancer cells, have anticancer properties in many different types of biological pathways. These molecular mechanisms in cancer cells include the suppression of cell growth and proliferation, deterioration of the cell cycle arrest, the start of apoptosis, antimetastasis, and antiangiogenic impact. Therefore, the aim of the present review summarised the antiproliferative and anticarcinogenic qualities of cervical cancer of emodin. ,Priyanka S. Lande ... Leena P. Joge [PublishedText] => Published [IsEdit] => 0 [AccountId] => 77 [Zh] => 1 ) [163] => Array ( [ArticleId] => 759 [Create_Time] => 2023-08-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202308/20230831082402.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002163/1002163.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002163/1002163.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002163/1002163_cover.png [JournalsId] => 4 [Title] => Clinical and mutational profile of AT-rich interaction domain 1A-mutated cancers [Abstract] => Aim: AT-rich interaction domain 1A (ARID1A) encodes a key component of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex that participates in gene expression. ARID1A alter [AbstractComplete] =>AT-rich interaction domain 1A (ARID1A) encodes a key component of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex that participates in gene expression. ARID1A alterations are quite common among cancer patients, although their role remains debated. The aim of this article was to study ARID1A-mutated cancer patients.
Molecular and clinical data of cancer patients evaluated at Phase 1 Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS were collected. Molecular analyses were performed using FoundationOne® CDx (Foundation Medicine Inc., Cambridge, MA, United States). Cancer patients with at least one molecular alteration in ARID1A gene were identified as ARID1A+.
Among the 270 patients undergoing molecular analysis, we found 25 (9%) with at least one pathogenic alteration in ARID1A. The vast majority of these patients were female (84%). The median age at diagnosis was 59; most of the cancers (15, 60%) were gynecological (especially endometrioid endometrial cancers and clear cell ovarian cancers), diagnosed at an early stage. Frameshift alterations in ARID1A were the most common (19/31, 61%) alterations. The median number of mutations in ARID1A+ population was higher compared to ARID1A– population (6 vs. 4), as well as tumor mutational burden (TMB) [20 mutations/megabase (mut/Mb) vs. 1.26 mut/Mb]. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphatase and tensin homolog (PTEN), catenin beta 1 (CTNNB1), and lysine methyltransferase 2D (MLL2) mutations were enriched in ARID1A+ population. In this cohort, ARID1A did not display any relation with response to platinum chemotherapy. Cancers with double alterations in ARID1A (ARID1A2+) were all gynecological cancers (83% endometrioid endometrial cancers).
This analysis provides clinical and molecular details about the phenotypes of ARID1A+ cancers, in particular the subgroup of gynecologic cancers. The high frequency of concurrent mutations in the phosphoinositide 3-kinase (PI3K) pathway among endometrioid endometrial cancers may support the proposal of a new treatment strategy based on the combination of ataxia telangiectasia and Rad3-related (ATR) inhibitor and PIK3CA inhibitor.
Interferon (IFN)-stimulated gene 15 (ISG15) is a member of the ubiquitin-like (UBL) protein family that can modify specific proteins via a catalytic process called ISGylation. This posttranslational modification can modulate the stability of the ISGylated proteins and protein-protein interactions. Some proteins modified by ISG15 have been identified in malignant neoplasms, suggesting the functional relevance of ISGylation in cancer. This review discusses the ISGylated proteins reported in malignant neoplasms that suggest the potential of ISG15 as a biomarker and therapeutic target in cancer.
[Names] => Angeles C. Tecalco-Cruz, Jesús Zepeda-Cervantes [Doi] => 10.37349/etat.2023.00162 [Published] => August 31, 2023 [Viewed] => 623 [Downloaded] => 19 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00162 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 132 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:699–715 [Recommend] => 0 [Keywords] => Interferon-stimulated gene 15, ISGylation, cancer [DetailTitle] => Posttranslational Modifications in Health and Disease [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/132 [Id] => 1002162 [ris] => https://www.explorationpub.com/uploads/Article/A1002162/d8db3670c2aacfbdd588e026881089a3.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002162/9a62625d8dc4cc0dc9a69a6e2714026e.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Tecalco-Cruz AC, Zepeda-Cervantes J. Protein ISGylation: a posttranslational modification with implications for malignant neoplasms. Explor Target Antitumor Ther. 2023;4:699–715. https://doi.org/10.37349/etat.2023.00162 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-08-30 08:01:46 [Bib_Time] => 2023-08-30 08:01:46 [KeysWordContens] => Protein ISGylation: a posttranslational modification with implications for malignant neoplasms, Interferon-stimulated gene 15, ISGylation, cancer, Interferon (IFN)-stimulated gene 15 (ISG15) is a member of the ubiquitin-like (UBL) protein family that can modify specific proteins via a catalytic process called ISGylation. This posttranslational modification can modulate the stability of the ISGylated proteins and protein-protein interactions. Some proteins modified by ISG15 have been identified in malignant neoplasms, suggesting the functional relevance of ISGylation in cancer. This review discusses the ISGylated proteins reported in malignant neoplasms that suggest the potential of ISG15 as a biomarker and therapeutic target in cancer. ,Angeles C. Tecalco-Cruz, Jesús Zepeda-Cervantes [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [165] => Array ( [ArticleId] => 781 [Create_Time] => 2023-09-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202309/20230901025029.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002167/1002167.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002167/1002167.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002167/1002167_Cover.png [JournalsId] => 4 [Title] => Aflatoxin B1-DNA adducts modify the effects of post-operative adjuvant transarterial chemoembolization improving hepatocellular carcinoma prognosis [Abstract] => Aim: DNA damage involves in the carcinogenesis of some cancer and may act as a target for therapeutic intervention of cancers. However, it is unclear whether aflatoxin B1 (AFB1)-DNA adducts (ADAs) [AbstractComplete] =>DNA damage involves in the carcinogenesis of some cancer and may act as a target for therapeutic intervention of cancers. However, it is unclear whether aflatoxin B1 (AFB1)-DNA adducts (ADAs), an important kind of DNA damage caused by AFB1, affect the efficiency of post-operative adjuvant transarterial chemoembolization (po-TACE) treatment improving hepatocellular carcinoma (HCC) survival.
A hospital-based retrospective study, including 318 patients with Barcelona Clinic Liver Cancer (BCLC)-C stage HCC from high AFB1 exposure areas, to investigate the potential effects of ADAs in the tissues with HCC on po-TACE treatment. The amount of ADAs in the cancerous tissues was tested by competitive enzyme-linked immunosorbent assay (c-ELISA).
Among these patients with HCC, the average amount of ADAs was 3.00 µmol/mol ± 1.51 µmol/mol DNA in their tissues with cancer. For these patients, increasing amount of ADAs was significantly associated with poorer overall survival (OS) and tumor reoccurrence-free survival (RFS), with corresponding death risk (DR) of 3.69 (2.78–4.91) and tumor recurrence risk (TRR) of 2.95 (2.24–3.88). The po-TACE therapy can efficiently improve their prognosis [DR = 0.59 (0.46–0.76), TRR = 0.63 (0.49–0.82)]. Interestingly, this improving role was more noticeable among these patients with high ADAs [DR = 0.36 (0.24–0.53), TRR = 0.40 (0.28–0.59)], but not among those with low ADAs (P > 0.05).
These results suggest that increasing ADAs in the cancerous tissues may be beneficial for po-TACE in ameliorating the survival of patients with HCC.
Delineate structure-based inhibition of colony-stimulating factor-1 receptor (CSF1R) by small molecule CSF1R inhibitors in clinical development for target identification and potential lead optimization in cancer therapeutics since CSF1R is a novel predictive biomarker for immunotherapy in cancer.
Compounds were in silico modelled by induced fit docking protocol in a molecular operating environment (MOE, MOE.v.2015). The 3-dimensional (3D) X-ray crystallized structure of CSF1R kinase (Protein Databank, ID 4R7H) was obtained from Research Collaboratory for Structural Bioinformatics (RSCB) Protein Databank. The 3D conformers of edicotinib, DCC-3014, ARRY-382, BLZ-945, chiauranib, dovitinib, and sorafenib were obtained from PubChem Database. These structures were modelled in Amber10:EHT molecular force field, and quick prep application was used to correct and optimize the structures for missing residues, H-counts, termini capping, and alternates. The binding site was defined within the vicinity of the co-crystallized ligand of CSF1R kinase. The compounds were docked by the triangular matcher placement method and ranked by the London dG scoring function. The docked poses were further refined by the induced fit method. The pose with the lowest binding score (ΔG) was used to model the ligand interaction profile in Discovery Studio Visualizer v17.2. The co-crystallized ligand was docked in its apo conformation, and root-mean-square deviation was computed to validate the docking protocol.
All 7 CSF1R inhibitors interact with residue Met637 exhibiting selectivity except for edicotinib. The inhibitors maintain CSF1R in an auto-inhibitory conformation by interacting with Asp797 of the Asp-Phe-Gly (DFG) motif and/or hindering the conserved salt bridge formed between Glu633 and Lys616 thus stabilizing the activation loop, or interacting with tryptophan residue (Trp550) in the juxtamembrane domain. DCC-3014, ARRY-382, BLZ-945, and sorafenib bind with the lowest binding energy with CSF1R kinase.
Pyrimidines are potent inhibitors that interact with CSF1R residues. DCC-3014 and ARRY-382 exhibit exceptional pharmaceutical potential exhibiting great structural stability and affinity.
In renal cell carcinoma (RCC), tumor heterogeneity generated challenges to biomarker development and therapeutic management, often becoming responsible for primary and acquired drug resistance. This study aimed to assess the inter-tumoral, intra-tumoral, and intra-lesional heterogeneity of known druggable targets in metastatic RCC (mRCC).
The RIVELATOR study was a monocenter retrospective analysis of biological samples from 25 cases of primary RCC and their paired pulmonary metastases. The biomarkers analyzed included MET, mTOR, PD-1/PD-L1 pathways and the immune context.
High multi-level heterogeneity was demonstrated. MET was the most reliable biomarker, with the lowest intratumor heterogeneity: the positive mutual correlation between MET expression in primary tumors and their metastases had a significantly proportional intensity (P = 0.038). The intratumor heterogeneity grade was significantly higher for the mTOR pathway proteins. Combined immunophenotypical expression patterns and their correlations with the immune context were uncovered [i.e., mTOR expression in the metastases positively correlated with PD-L1 expression in tumor-infiltrating lymphocytes (TILs), P = 0.019; MET expression was related to PD-1 expression on TILs (P = 0.041, ρ = 0.41) and peritumoral lymphocytes (RILs; P = 0.013, ρ = 0.49)], suggesting the possibility of predicting drug response or resistance to tyrosine kinase, mTOR, or immune checkpoint inhibitors.
In mRCC, multiple and multi-level assays of potentially predictive biomarkers are needed for their reliable translation into clinical practice. The easy-to-use immunohistochemical method of the present study allowed the identification of different combined expression patterns, providing cues for planning the management of systemic treatment combinations and sequences in an mRCC patient population. The quantitative heterogeneity of the investigated biomarkers suggests that multiple intralesional assays are needed to consider the assessment reliable for clinical considerations.
Histone deacetylases (HDACs) are a class of zinc (Zn)-dependent metalloenzymes that are responsible for epigenetic modifications. HDACs are largely associated with histone proteins that regulate gene expression at the DNA level. This tight regulation is controlled by acetylation [via histone acetyl transferases (HATs)] and deacetylation (via HDACs) of histone and non-histone proteins that alter the coiling state of DNA, thus impacting gene expression as a downstream effect. For the last two decades, HDACs have been studied extensively and indicated in a range of diseases where HDAC dysregulation has been strongly correlated with disease emergence and progression—most prominently, cancer, neurodegenerative diseases, HIV, and inflammatory diseases. The involvement of HDACs as regulators in these biochemical pathways established them as an attractive therapeutic target. This review summarizes the drug development efforts exerted to create HDAC inhibitors (HDACis), specifically class I HDACs, with a focus on the medicinal chemistry, structural design, and pharmacology aspects of these inhibitors.
[Names] => Diaaeldin I. Abdallah ... Patrick T. Gunning [Doi] => 10.37349/etat.2023.00166 [Published] => August 31, 2023 [Viewed] => 1218 [Downloaded] => 50 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00166 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 132 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:757–779 [Recommend] => 0 [Keywords] => Histone deacetylases, zinc-binding group, cap group, epigenetic regulation, small-molecule inhibitors, medicinal chemistry [DetailTitle] => Posttranslational Modifications in Health and Disease [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/132 [Id] => 1002166 [ris] => https://www.explorationpub.com/uploads/Article/A1002166/b5aa98e80f31a627c4e720580f2c5963.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002166/37cf5e64562f6106e31b0ec675312881.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Abdallah DI, de Araujo ED, Patel NH, Hasan LS, Moriggl R, Krämer OH, et al. Medicinal chemistry advances in targeting class I histone deacetylases. Explor Target Antitumor Ther. 2023;4:757–79. https://doi.org/10.37349/etat.2023.00166 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-08-30 10:20:41 [Bib_Time] => 2023-08-30 10:20:41 [KeysWordContens] => Medicinal chemistry advances in targeting class I histone deacetylases, Histone deacetylases, zinc-binding group, cap group, epigenetic regulation, small-molecule inhibitors, medicinal chemistry, Histone deacetylases (HDACs) are a class of zinc (Zn)-dependent metalloenzymes that are responsible for epigenetic modifications. HDACs are largely associated with histone proteins that regulate gene expression at the DNA level. This tight regulation is controlled by acetylation [via histone acetyl transferases (HATs)] and deacetylation (via HDACs) of histone and non-histone proteins that alter the coiling state of DNA, thus impacting gene expression as a downstream effect. For the last two decades, HDACs have been studied extensively and indicated in a range of diseases where HDAC dysregulation has been strongly correlated with disease emergence and progression—most prominently, cancer, neurodegenerative diseases, HIV, and inflammatory diseases. The involvement of HDACs as regulators in these biochemical pathways established them as an attractive therapeutic target. This review summarizes the drug development efforts exerted to create HDAC inhibitors (HDACis), specifically class I HDACs, with a focus on the medicinal chemistry, structural design, and pharmacology aspects of these inhibitors. ,Diaaeldin I. Abdallah ... Patrick T. Gunning [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [169] => Array ( [ArticleId] => 800 [Create_Time] => 2023-09-07 [zipUrl] => https://www.explorationpub.com/uploads/zip/202309/20230907005747.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002168/1002168.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002168/1002168.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002168/1002168_cover.png [JournalsId] => 4 [Title] => A single experience in the conduction of clinical trial during COronaVIrusDisease-2019 pandemic [Abstract] => Aim: From the start of the pandemic, several aspects of healthcare policies changed, not least the clinical trials management from recruiting capabilities to the protocol compliance in terms of s [AbstractComplete] =>From the start of the pandemic, several aspects of healthcare policies changed, not least the clinical trials management from recruiting capabilities to the protocol compliance in terms of schedule of procedures, follow-up visits, staff constraints and monitoring. This study aims to assess the impact of the COronaVIrusDisease-2019 (COVID-19) pandemic in the conduction of clinical trials at the site of clinical oncology, Ancona (Italy), to identify the strengths and weaknesses upfront the past emergency, and to select better strategies for future similar situations.
Data from February to July of the years 2019, 2020 and 2021 were collected and three practical parameters of the trial unit were investigated: milestones, performance, and impact.
The trials mean numbers were 18, 24, and 23, in 2019, 2020, and 2021 respectively. The pre-Site Initiation Visit (PRE-SIV) rate grew from 66.6% in 2019 to 95.5% in 2021 with a deflection in 2020. Protocol deviations were 40 in the period February-July 2019, in the same period of 2020 the number of deviations increased due to COVID related ones, then there was a significant total decrease in February-July 2021. In 2020 and 2021, all the investigator meetings were online.
The growing number of remote Site Initiation Visit (SIV) and meetings over the last 3 years suggests the feasibility of the on-line processes. The significant reduction in protocol deviations during 2021 is probably due to an under check of data during a pandemic. But that is also a possible key indicator of the coping strategy made out by clinical oncology to guarantee the continuity of care in clinical trials and to offer new opportunities of cancer care in a bad scenario such as a pandemic one.
Malignant tumors of the external auditory canal (EAC) are rare neoplasms that appear in the head and neck area. A common feature of these malignancies is their rarity, as well as their delayed diagnosis due to the appearance of non-specific symptoms that mimic various benign otologic conditions. The reported histological types of cancer of the external ear are: squamous cell carcinoma, basal cell carcinoma, malignant melanoma, Merkel cell carcinoma, angiosarcoma, adnexal carcinoma (including ceruminous adenocarcinoma and adenoid cystic carcinoma), and lymphoma (Lancet Oncol. 2005;6:411–20. doi: 10.1016/S1470-2045(05)70208-4). Several therapeutic interventions have been proposed, primarily orientated towards the cure of the patient, placing the surgical excision of the lesions at the tip of the spear. Subsequently and depending on the clinical stage and the pathological characteristics of the tumor, radiation, chemotherapy, a combination thereof, or some form of palliative treatment for particularly advanced cases, may be recommended. The aim of all the above-mentioned approaches is the complete resection of the mass with negative surgical margins along with lymph node dissection, the elimination of any residual disease or metastasis, and the improvement of survival. The anatomical complexity of the region will always remain a demanding challenge. Nevertheless, advances in the fields of ear microsurgery, imaging, radiation, molecular biology, and genomics have led to remarkable outcomes compared to the past, with a view to the patient’s quality of life. Large, well-organized, and prospective studies with the participation of multiple centers in contrast to existing retrospective studies with a limited number of patients will help to establish universally accepted guidelines. The exploration of the molecular and genetic background of these cancers in conjunction with the search for new biomarkers and target molecules seems promising for providing upgraded and more personalized treatment modalities for the future.
[Names] => Pinelopi Samara ... Ioannis Athanasopoulos [Doi] => 10.37349/etat.2023.00169 [Published] => September 21, 2023 [Viewed] => 968 [Downloaded] => 25 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00169 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 103 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:801–811 [Recommend] => 0 [Keywords] => External auditory canal cancer, ear cancer, squamous cell carcinoma, ceruminous adenocarcinoma, surgery, radiotherapy, chemotherapy, biomarkers [DetailTitle] => Biomarkers for Personalized and Precise Cancer Diagnosis and Treatment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/103 [Id] => 1002169 [ris] => https://www.explorationpub.com/uploads/Article/A1002169/7d6a1097b2b2382823f2666fca88446f.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002169/e69d3d48b49a8e741802abeffb8bba6f.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Samara P, Athanasopoulos M, Goulioumis A, Athanasopoulos I. Malignant tumors of the external auditory canal: diagnosis, treatment, genetic landscape, biomarkers, and clinical outcome. Explor Target Antitumor Ther. 2023;4:801–11. https://doi.org/10.37349/etat.2023.00169 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-11-01 01:37:49 [Bib_Time] => 2023-11-01 01:37:49 [KeysWordContens] => Malignant tumors of the external auditory canal: diagnosis, treatment, genetic landscape, biomarkers, and clinical outcome, External auditory canal cancer, ear cancer, squamous cell carcinoma, ceruminous adenocarcinoma, surgery, radiotherapy, chemotherapy, biomarkers, Malignant tumors of the external auditory canal (EAC) are rare neoplasms that appear in the head and neck area. A common feature of these malignancies is their rarity, as well as their delayed diagnosis due to the appearance of non-specific symptoms that mimic various benign otologic conditions. The reported histological types of cancer of the external ear are: squamous cell carcinoma, basal cell carcinoma, malignant melanoma, Merkel cell carcinoma, angiosarcoma, adnexal carcinoma (including ceruminous adenocarcinoma and adenoid cystic carcinoma), and lymphoma (Lancet Oncol. 2005;6:411–20. doi: 10.1016/S1470-2045(05)70208-4). Several therapeutic interventions have been proposed, primarily orientated towards the cure of the patient, placing the surgical excision of the lesions at the tip of the spear. Subsequently and depending on the clinical stage and the pathological characteristics of the tumor, radiation, chemotherapy, a combination thereof, or some form of palliative treatment for particularly advanced cases, may be recommended. The aim of all the above-mentioned approaches is the complete resection of the mass with negative surgical margins along with lymph node dissection, the elimination of any residual disease or metastasis, and the improvement of survival. The anatomical complexity of the region will always remain a demanding challenge. Nevertheless, advances in the fields of ear microsurgery, imaging, radiation, molecular biology, and genomics have led to remarkable outcomes compared to the past, with a view to the patient’s quality of life. Large, well-organized, and prospective studies with the participation of multiple centers in contrast to existing retrospective studies with a limited number of patients will help to establish universally accepted guidelines. The exploration of the molecular and genetic background of these cancers in conjunction with the search for new biomarkers and target molecules seems promising for providing upgraded and more personalized treatment modalities for the future. ,Pinelopi Samara ... Ioannis Athanasopoulos [PublishedText] => Published [IsEdit] => 0 [AccountId] => 77 [Zh] => 1 ) [171] => Array ( [ArticleId] => 817 [Create_Time] => 2023-10-11 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231011091036.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002171/1002171.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002171/1002171.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002171/1002171_cover.png [JournalsId] => 4 [Title] => Understanding the feasibility of chemotherapeutic and immunotherapeutic targets against non-small cell lung cancers: an update of resistant responses and recent combinatorial therapies [Abstract] => Despite consistent progress in prompt diagnosis and curative therapies in the last decade, lung cancer (LC) continues to threaten mankind, accounting for nearly twice the casualties compared to pros [AbstractComplete] =>Despite consistent progress in prompt diagnosis and curative therapies in the last decade, lung cancer (LC) continues to threaten mankind, accounting for nearly twice the casualties compared to prostate, breast, and other cancers. Statistics associate ~25% of 2021 cancer-related deaths with LC, more than 80% of which are explicitly caused by tobacco smoking. Prevailing as small and non-small cell pathologies, with respective occurring frequency of nearly 15% and 80–85%, non-small cell LCs (NSCLCs) are prominently distinguished into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), subtypes. Since the first use of epidermal growth factor receptor (EGFR) inhibitor gefitinib for NSCLC treatment in 2002, immense progress has been made for targeted therapies with the next generation of drugs spanning across the chronological generations of small molecule inhibitors. The last two years have overseen the clinical approval of more than 10 therapeutic agents as first-line NSCLC medications. However, uncertain mutational aberrations as well as systemic resistant responses, and abysmal overall survival curtail the combating efficacies. Of late, immune checkpoint inhibitors (ICIs) against various molecules including programmed cell death-1 (PD-1) and its ligand (PD-L1) have been demonstrated as reliable LC treatment targets. Keeping these aspects in mind, this review article discusses the success of NSCLC chemo and immunotherapies with their characteristic effectiveness and future perspectives.
[Names] => Parth Malik ... Tapan Kumar Mukherjee [Doi] => 10.37349/etat.2023.00171 [Published] => October 10, 2023 [Viewed] => 813 [Downloaded] => 30 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00171 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 126 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:850–895 [Recommend] => 0 [Keywords] => Lung cancer, immunotherapy, chemotherapy, non-small cell lung cancer, immune checkpoint inhibitors, adenocarcinoma, squamous cell carcinoma [DetailTitle] => Integrated Approaches for Non-Small-Cell Lung Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/126 [Id] => 1002171 [ris] => https://www.explorationpub.com/uploads/Article/A1002171/51661ad39df36f5a68829aefd0c433c3.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002171/4480f84f0f3c60949bebb414b3a0514e.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Malik P, Rani R, Solanki R, Patel VH, Mukherjee TK. Understanding the feasibility of chemotherapeutic and immunotherapeutic targets against non-small cell lung cancers: an update of resistant responses and recent combinatorial therapies. Explor Target Antitumor Ther. 2023;4:850–95. https://doi.org/10.37349/etat.2023.00171 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-10-11 09:10:36 [Bib_Time] => 2023-10-11 09:10:36 [KeysWordContens] => Understanding the feasibility of chemotherapeutic and immunotherapeutic targets against non-small cell lung cancers: an update of resistant responses and recent combinatorial therapies, Lung cancer, immunotherapy, chemotherapy, non-small cell lung cancer, immune checkpoint inhibitors, adenocarcinoma, squamous cell carcinoma, Despite consistent progress in prompt diagnosis and curative therapies in the last decade, lung cancer (LC) continues to threaten mankind, accounting for nearly twice the casualties compared to prostate, breast, and other cancers. Statistics associate ~25% of 2021 cancer-related deaths with LC, more than 80% of which are explicitly caused by tobacco smoking. Prevailing as small and non-small cell pathologies, with respective occurring frequency of nearly 15% and 80–85%, non-small cell LCs (NSCLCs) are prominently distinguished into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), subtypes. Since the first use of epidermal growth factor receptor (EGFR) inhibitor gefitinib for NSCLC treatment in 2002, immense progress has been made for targeted therapies with the next generation of drugs spanning across the chronological generations of small molecule inhibitors. The last two years have overseen the clinical approval of more than 10 therapeutic agents as first-line NSCLC medications. However, uncertain mutational aberrations as well as systemic resistant responses, and abysmal overall survival curtail the combating efficacies. Of late, immune checkpoint inhibitors (ICIs) against various molecules including programmed cell death-1 (PD-1) and its ligand (PD-L1) have been demonstrated as reliable LC treatment targets. Keeping these aspects in mind, this review article discusses the success of NSCLC chemo and immunotherapies with their characteristic effectiveness and future perspectives. ,Parth Malik ... Tapan Kumar Mukherjee [PublishedText] => Published [IsEdit] => 0 [AccountId] => 77 [Zh] => 1 ) [172] => Array ( [ArticleId] => 818 [Create_Time] => 2023-10-11 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231011032457.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002172/1002172.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002172/1002172.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002172/1002172-cover.png [JournalsId] => 4 [Title] => Exploring the implications of modified advanced lung cancer inflammation index on outcomes in patients with advanced non-small cell lung cancer [Abstract] => Aim: Sarcopenia and skeletal muscle density (SMD) have been shown to be both predictive and prognostic marker in oncology. Advanced lung cancer inflammation index (ALI) has been shown to predict [AbstractComplete] =>Sarcopenia and skeletal muscle density (SMD) have been shown to be both predictive and prognostic marker in oncology. Advanced lung cancer inflammation index (ALI) has been shown to predict overall survival (OS) in small cell lung cancer (SCLC). Computed tomography (CT) enables skeletal muscle to be quantified, whereas body mass index (BMI) cannot accurately reflect body composition. The purpose was to evaluate the prognostic value of modified ALI (mALI) using CT-determined third lumbar vertebra (L3) muscle index beyond original ALI and see the interaction between sarcopenia, SMD, neutrophil-lymphocyte ratio (NLR), ALI and mALI at baseline and post 4 cycles of chemotherapy and their effects on OS and progress free survival (PFS) in patients with advanced non-SCLC (NSCLC).
This retrospective study consisted of a total of 285 advanced NSCLC patients. The morphometric parameters such as SMD, skeletal muscle index (SMI) and fat-free mass (FFM) were measured by CT at the L3 vertebra. ALI was defined as BMI × serum albumin/NLR and mALI was defined as SMI × serum albumin/NLR.
Sarcopenia was observed in over 70% of patients across all BMI categories. Patients having sarcopenia suffered from a higher incidence of chemotherapeutic drug toxicities but this was not found to be statistically significant. Concordance was seen between ALI and mALI in the pre-treatment setting and this was statistically significant. A significant proportion of patients with poor ALI (90.9%), poor pre-chemotherapy mALI (91.3%) and poor post-chemotherapy mALI (89%) had poor NLR and each of them was statistically significant.
In both univariate and multivariate analyses, this study demonstrated the statistical significance of sarcopenia, SMD, and mALI as predictive factors for OS. Additionally, sarcopenia and SMD were also found to be statistically significant factors in predicting PFS. These biomarkers could potentially help triage patients for active nutritional intervention for better outcomes.
From attributing mutations to cancers with the advent of cutting-edge genetic technology in recent decades, to re-searching the age-old theory of intrinsic metabolic shift of cancers (Warburg’s glycolysis), the quest for a precise panacea for mainly the metastatic cancers, remains incessant. This review delineates the advanced glycation end product (AGE)-receptor for AGE (RAGE) pathway driven intricate oncogenic cues, budding from the metabolic (glycolytic) reliance of tumour cells, branching into metastatic emergence of malignancies. Strong AGE-RAGE concomitance in metastasis, chemo-resistance and cancer resurgence adversely incite disease progression and patient mortality. At the conjunction of metabolic and metastatic shift of cancers, are the “glycolytically” generated AGEs and AGE-activated RAGE, instigating aberrant molecular pathways, culminating in aggressive malignancies. AGEs as by-products of metabolic insurgence, modify the metabolome, epigenome and microbiome, besides coercing the inter-, intra- and extra-cellular micro-milieu conducive for oncogenic events like epithelial-mesenchymal transition (EMT). AGE-RAGE synergistically elicit ATP surge for surplus energy, autophagy for apoptotic evasion and chemo-resistance, insulin-like growth factor 1 (IGF-1) for meta-inflammation and angiogenesis, high mobility group box-1 (HMGB1) for immune tolerance, S100 proteins for metastasis, and p53 protein attenuation for tumour suppression. AGEs are pronouncedly reported in invasive forms of breast, prostate, colon and pancreatic cancers, higher in patients with cancer than healthy counterparts, and higher in advanced stage than localized phase. Hence, the investigation of person-specific presence of AGEs, soluble RAGE and AGE-activated RAGE can be advocated as impending bio-markers for diagnostic, prognostic and therapeutic purposes, to predict cancer risk in patients with diabetes, obesity, metabolic syndrome as well as general population, to monitor prognosis and metastasis in patients with cancer, and to reckon complications in cancer survivors. Furthermore, clinical reports of exogenous (dietary) and endogenous (internally formed) AGEs in cancer patients, and contemporary clinical trials involving AGE-RAGE axis in cancer are underlined with theranostic implications.
[Names] => Gowri Palanissami, Solomon F.D. Paul [Doi] => 10.37349/etat.2023.00170 [Published] => September 28, 2023 [Viewed] => 1658 [Downloaded] => 26 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00170 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 103 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:812–849 [Recommend] => 0 [Keywords] => RAGE, AGEs, high mobility group box-1, S100, cancer, glycation, epigenome, microbiome [DetailTitle] => Biomarkers for Personalized and Precise Cancer Diagnosis and Treatment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/103 [Id] => 1002170 [ris] => https://www.explorationpub.com/uploads/Article/A1002170/ed27b83326153099d0089e46dc492cae.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002170/92a83f78bd1e37a2df932d9fe5907742.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Palanissami G, Paul SFD. AGEs and RAGE: metabolic and molecular signatures of the glycation-inflammation axis in malignant or metastatic cancers. Explor Target Antitumor Ther. 2023;4:812–49. https://doi.org/10.37349/etat.2023.00170 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-09-21 00:33:50 [Bib_Time] => 2023-09-21 00:33:50 [KeysWordContens] => AGEs and RAGE: metabolic and molecular signatures of the glycation-inflammation axis in malignant or metastatic cancers, RAGE, AGEs, high mobility group box-1, S100, cancer, glycation, epigenome, microbiome, From attributing mutations to cancers with the advent of cutting-edge genetic technology in recent decades, to re-searching the age-old theory of intrinsic metabolic shift of cancers (Warburg’s glycolysis), the quest for a precise panacea for mainly the metastatic cancers, remains incessant. This review delineates the advanced glycation end product (AGE)-receptor for AGE (RAGE) pathway driven intricate oncogenic cues, budding from the metabolic (glycolytic) reliance of tumour cells, branching into metastatic emergence of malignancies. Strong AGE-RAGE concomitance in metastasis, chemo-resistance and cancer resurgence adversely incite disease progression and patient mortality. At the conjunction of metabolic and metastatic shift of cancers, are the “glycolytically” generated AGEs and AGE-activated RAGE, instigating aberrant molecular pathways, culminating in aggressive malignancies. AGEs as by-products of metabolic insurgence, modify the metabolome, epigenome and microbiome, besides coercing the inter-, intra- and extra-cellular micro-milieu conducive for oncogenic events like epithelial-mesenchymal transition (EMT). AGE-RAGE synergistically elicit ATP surge for surplus energy, autophagy for apoptotic evasion and chemo-resistance, insulin-like growth factor 1 (IGF-1) for meta-inflammation and angiogenesis, high mobility group box-1 (HMGB1) for immune tolerance, S100 proteins for metastasis, and p53 protein attenuation for tumour suppression. AGEs are pronouncedly reported in invasive forms of breast, prostate, colon and pancreatic cancers, higher in patients with cancer than healthy counterparts, and higher in advanced stage than localized phase. Hence, the investigation of person-specific presence of AGEs, soluble RAGE and AGE-activated RAGE can be advocated as impending bio-markers for diagnostic, prognostic and therapeutic purposes, to predict cancer risk in patients with diabetes, obesity, metabolic syndrome as well as general population, to monitor prognosis and metastasis in patients with cancer, and to reckon complications in cancer survivors. Furthermore, clinical reports of exogenous (dietary) and endogenous (internally formed) AGEs in cancer patients, and contemporary clinical trials involving AGE-RAGE axis in cancer are underlined with theranostic implications. ,Gowri Palanissami, Solomon F.D. Paul [PublishedText] => Published [IsEdit] => 0 [AccountId] => 87 [Zh] => 1 ) [174] => Array ( [ArticleId] => 819 [Create_Time] => 2023-10-12 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231011081623.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002173/1002173.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002173/1002173.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002173/1002173_cover.png [JournalsId] => 4 [Title] => Molecular interaction of metastasis suppressor genes and tumor microenvironment in breast cancer [Abstract] => Breast cancer (BC) is a leading cause of cancer-related deaths in women worldwide where the process of metastasis is a major contributor to the mortality associated with this disease. Metastasis sup [AbstractComplete] =>Breast cancer (BC) is a leading cause of cancer-related deaths in women worldwide where the process of metastasis is a major contributor to the mortality associated with this disease. Metastasis suppressor genes are a group of genes that play a crucial role in preventing or inhibiting the spread of cancer cells. They suppress the metastasis process by inhibiting colonization and by inducing dormancy. These genes function by regulating various cellular processes in the tumor microenvironment (TME), such as cell adhesion, invasion, migration, and angiogenesis. Dysregulation of metastasis suppressor genes can lead to the acquisition of an invasive and metastatic phenotype and lead to poor prognostic outcomes. The components of the TME generally play a necessary in the metastasis progression of tumor cells. This review has identified and elaborated on the role of a few metastatic suppressors associated with the TME that have been shown to inhibit metastasis in BC by different mechanisms, such as blocking certain cell signaling molecules involved in cancer cell migration, invasion, enhancing immune surveillance of cancer cells, and promoting the formation of a protective extracellular matrix (ECM). Understanding the interaction of metastatic suppressor genes and the components of TME has important implications for the development of novel therapeutic strategies to target the metastatic cascade. Targeting these genes or their downstream signaling pathways offers a promising approach to inhibiting the spread of cancer cells and improves patient outcomes.
[Names] => Sathammai Sathappa Supuramanian ... Sitaram Harihar [Doi] => 10.37349/etat.2023.00173 [Published] => October 11, 2023 [Viewed] => 883 [Downloaded] => 28 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00173 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 113 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:912–932 [Recommend] => 0 [Keywords] => Tumor microenvironment, metastasis suppressor genes, breast cancer, breast cancer metastasis suppressor 1 [DetailTitle] => Therapeutic Targeting of the Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/113 [Id] => 1002173 [ris] => https://www.explorationpub.com/uploads/Article/A1002173/01c293b07313c0fa339bb15beb61db87.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002173/42906e3f25bbceff0c190ae8f1217f0c.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Supuramanian SS, Dsa S, Harihar S. Molecular interaction of metastasis suppressor genes and tumor microenvironment in breast cancer. Explor Target Antitumor Ther. 2023;4:912–32. https://doi.org/10.37349/etat.2023.00173 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-09-21 07:14:02 [Bib_Time] => 2023-09-21 07:14:02 [KeysWordContens] => Molecular interaction of metastasis suppressor genes and tumor microenvironment in breast cancer, Tumor microenvironment, metastasis suppressor genes, breast cancer, breast cancer metastasis suppressor 1, Breast cancer (BC) is a leading cause of cancer-related deaths in women worldwide where the process of metastasis is a major contributor to the mortality associated with this disease. Metastasis suppressor genes are a group of genes that play a crucial role in preventing or inhibiting the spread of cancer cells. They suppress the metastasis process by inhibiting colonization and by inducing dormancy. These genes function by regulating various cellular processes in the tumor microenvironment (TME), such as cell adhesion, invasion, migration, and angiogenesis. Dysregulation of metastasis suppressor genes can lead to the acquisition of an invasive and metastatic phenotype and lead to poor prognostic outcomes. The components of the TME generally play a necessary in the metastasis progression of tumor cells. This review has identified and elaborated on the role of a few metastatic suppressors associated with the TME that have been shown to inhibit metastasis in BC by different mechanisms, such as blocking certain cell signaling molecules involved in cancer cell migration, invasion, enhancing immune surveillance of cancer cells, and promoting the formation of a protective extracellular matrix (ECM). Understanding the interaction of metastatic suppressor genes and the components of TME has important implications for the development of novel therapeutic strategies to target the metastatic cascade. Targeting these genes or their downstream signaling pathways offers a promising approach to inhibiting the spread of cancer cells and improves patient outcomes. ,Sathammai Sathappa Supuramanian ... Sitaram Harihar [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [175] => Array ( [ArticleId] => 821 [Create_Time] => 2023-10-25 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231025013143.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002174/1002174.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002174/1002174.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002174/1002174_cover.png [JournalsId] => 4 [Title] => Current role of artificial intelligence in head and neck cancer surgery: a systematic review of literature [Abstract] => Aim: Artificial intelligence (AI) is a new field of science in which computers will provide decisions-supporting tools to help doctors make difficult clinical choices. Recent AI applications in o [AbstractComplete] =>Artificial intelligence (AI) is a new field of science in which computers will provide decisions-supporting tools to help doctors make difficult clinical choices. Recent AI applications in otolaryngology include head and neck oncology, rhinology, neurotology, and laryngology. The aim of this systematic review is to describe the potential uses of AI in head and neck oncology with a special focus on the surgical field.
The authors performed a systematic review, in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, in the main medical databases, including PubMed, Scopus, and Cochrane Library, considering all original studies published until February 2023 about the role of AI in head and neck cancer surgery. The search strategy included a combination of the following terms: “artificial intelligence” or “machine learning” and “head and neck cancer”.
Overall, 303 papers were identified and after duplicate removal (12 papers) and excluding papers not written in English (1 paper) and off-topic (4 papers), papers were assessed for eligibility; finally, only 12 papers were included. Three main fields of clinical interest were identified: the most widely investigated included the role of AI in surgical margins assessment (7 papers); the second most frequently evaluated topic was complications assessment (4 papers); finally, only one paper dealt with the indication of salvage laryngectomy after primary radiotherapy.
The authors report the first systematic review in the literature concerning the role of AI in head and neck cancer surgery. An increasing influx of AI applications to clinical problems in otolaryngology is expected, so specialists should be increasingly prepared to manage the constant changes. It will always remain critical for clinicians to use their skills and knowledge to critically evaluate the additional information provided by AI and make the final decisions on each patient.
Renal cell carcinoma (RCC) is one of the most life-threatening urinary malignancies displaying poor response to radiotherapy and chemotherapy. Although in the recent past there have been tremendous advancements in using targeted therapies for RCC, despite that it remains the most lethal urogenital cancer with a 5-year survival rate of roughly 76%. Timely diagnosis is still the key to prevent the progression of RCC into metastatic stages as well as to treat it. But due to the lack of definitive and specific diagnostic biomarkers for RCC and its asymptomatic nature in its early stages, it becomes very difficult to diagnose it. Reliable and distinct molecular markers can not only refine the diagnosis but also classifies the tumors into thier sub-types which can escort subsequent management and possible treatment for patients. Potential biomarkers can permit a greater degree of stratification of patients affected by RCC and help tailor novel targeted therapies. The review summarizes the most promising epigenetic [DNA methylation, microRNA (miRNA; miR), and long noncoding RNA (lncRNA)] and protein biomarkers that have been known to be specifically involved in diagnosis, cancer progression, and metastasis of RCC, thereby highlighting their utilization as non-invasive molecular markers in RCC. Also, the rationale and development of novel molecular targeted drugs and immunotherapy drugs [such as tyrosine kinase inhibitors and immune checkpoint inhibitors (ICIs)] as potential RCC therapeutics along with the proposed implication of these biomarkers in predicting response to targeted therapies will be discussed.
[Names] => Shruti Gupta, Shamsher Singh Kanwar [Doi] => 10.37349/etat.2023.00175 [Published] => October 25, 2023 [Viewed] => 659 [Downloaded] => 19 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00175 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 103 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:941–961 [Recommend] => 0 [Keywords] => Renal cell carcinoma, biomarkers targeted therapies, molecular medicine, DNA methylation, microRNA, long noncoding RNA [DetailTitle] => Biomarkers for Personalized and Precise Cancer Diagnosis and Treatment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/103 [Id] => 1002175 [ris] => https://www.explorationpub.com/uploads/Article/A1002175/51dd50b429f9778bdd8e1287d1b7d8bb.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002175/40a1b56ae342df3528c0248ad75f2c19.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Gupta S, Kanwar SS. Biomarkers in renal cell carcinoma and their targeted therapies: a review. 2023;4:941–61. https://doi.org/10.37349/etat.2023.00175 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-10-23 05:53:56 [Bib_Time] => 2023-10-19 05:00:50 [KeysWordContens] => Biomarkers in renal cell carcinoma and their targeted therapies: a review, Renal cell carcinoma, biomarkers targeted therapies, molecular medicine, DNA methylation, microRNA, long noncoding RNA, Renal cell carcinoma (RCC) is one of the most life-threatening urinary malignancies displaying poor response to radiotherapy and chemotherapy. Although in the recent past there have been tremendous advancements in using targeted therapies for RCC, despite that it remains the most lethal urogenital cancer with a 5-year survival rate of roughly 76%. Timely diagnosis is still the key to prevent the progression of RCC into metastatic stages as well as to treat it. But due to the lack of definitive and specific diagnostic biomarkers for RCC and its asymptomatic nature in its early stages, it becomes very difficult to diagnose it. Reliable and distinct molecular markers can not only refine the diagnosis but also classifies the tumors into thier sub-types which can escort subsequent management and possible treatment for patients. Potential biomarkers can permit a greater degree of stratification of patients affected by RCC and help tailor novel targeted therapies. The review summarizes the most promising epigenetic [DNA methylation, microRNA (miRNA; miR), and long noncoding RNA (lncRNA)] and protein biomarkers that have been known to be specifically involved in diagnosis, cancer progression, and metastasis of RCC, thereby highlighting their utilization as non-invasive molecular markers in RCC. Also, the rationale and development of novel molecular targeted drugs and immunotherapy drugs [such as tyrosine kinase inhibitors and immune checkpoint inhibitors (ICIs)] as potential RCC therapeutics along with the proposed implication of these biomarkers in predicting response to targeted therapies will be discussed. ,Shruti Gupta, Shamsher Singh Kanwar [PublishedText] => Published [IsEdit] => 0 [AccountId] => 57 [Zh] => 1 ) [177] => Array ( [ArticleId] => 857 [Create_Time] => 2023-10-25 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231026065011.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002176/1002176.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002176/1002176.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002176/1002176-cover.png [JournalsId] => 4 [Title] => Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses [Abstract] => A dysregulated circadian rhythm is significantly associated with cancer risk, as is aging. Both aging and circadian dysregulation show suppressed pineal melatonin, which is indicated in many studies [AbstractComplete] =>A dysregulated circadian rhythm is significantly associated with cancer risk, as is aging. Both aging and circadian dysregulation show suppressed pineal melatonin, which is indicated in many studies to be linked to cancer risk and progression. Another independently investigated aspect of the circadian rhythm is the cortisol awakening response (CAR), which is linked to stress-associated hypothalamus-pituitary-adrenal (HPA) axis activation. CAR and HPA axis activity are primarily mediated via activation of the glucocorticoid receptor (GR), which drives patterned gene expression via binding to the promotors of glucocorticoid response element (GRE)-expressing genes. Recent data shows that the GR can be prevented from nuclear translocation by the B cell lymphoma-2 (Bcl-2)-associated athanogene 1 (BAG-1), which translocates the GR to mitochondria, where it can have diverse effects. Melatonin also suppresses GR nuclear translocation by maintaining the GR in a complex with heat shock protein 90 (Hsp90). Melatonin, directly and/or epigenetically, can upregulate BAG-1, suggesting that the dramatic 10-fold decrease in pineal melatonin from adolescence to the ninth decade of life will attenuate the capacity of night-time melatonin to modulate the effects of the early morning CAR. The interactions of pineal melatonin/BAG-1/Hsp90 with the CAR are proposed to underpin how aging and circadian dysregulation are associated with cancer risk. This may be mediated via differential effects of melatonin/BAG-1/Hsp90/GR in different cells of microenvironments across the body, from which tumors emerge. This provides a model of cancer pathogenesis that better integrates previously disparate bodies of data, including how immune cells are regulated by cancer cells in the tumor microenvironment, at least partly via the cancer cell regulation of the tryptophan-melatonin pathway. This has a number of future research and treatment implications.
[Names] => George Anderson [Doi] => 10.37349/etat.2023.00176 [Published] => October 25, 2023 [Viewed] => 876 [Downloaded] => 20 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00176 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 216 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:962–993 [Recommend] => 0 [Keywords] => Tumor pathogenesis, melatonin, N-acetylserotonin, aryl hydrocarbon receptor, cortisol awakening response, hypothalamus-pituitary-adrenal axis, B cell lymphoma-2-associated athanogene 1, mitochondria [DetailTitle] => Novel Insights into Immunotherapy Targeting Tumor Microenvironment in Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/216 [Id] => 1002176 [ris] => https://www.explorationpub.com/uploads/Article/A1002176/00e35af22ac719499249dc5768437882.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002176/87c1e2f0699ffc8b4fecbdc1020c051f.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-26 [CitethisArticle] => Anderson G. Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses. Explor Target Antitumor Ther. 2023;4:962–93. https://doi.org/10.37349/etat.2023.00176 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-10-20 06:17:50 [Bib_Time] => 2023-10-20 06:17:50 [KeysWordContens] => Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses, Tumor pathogenesis, melatonin, N-acetylserotonin, aryl hydrocarbon receptor, cortisol awakening response, hypothalamus-pituitary-adrenal axis, B cell lymphoma-2-associated athanogene 1, mitochondria, A dysregulated circadian rhythm is significantly associated with cancer risk, as is aging. Both aging and circadian dysregulation show suppressed pineal melatonin, which is indicated in many studies to be linked to cancer risk and progression. Another independently investigated aspect of the circadian rhythm is the cortisol awakening response (CAR), which is linked to stress-associated hypothalamus-pituitary-adrenal (HPA) axis activation. CAR and HPA axis activity are primarily mediated via activation of the glucocorticoid receptor (GR), which drives patterned gene expression via binding to the promotors of glucocorticoid response element (GRE)-expressing genes. Recent data shows that the GR can be prevented from nuclear translocation by the B cell lymphoma-2 (Bcl-2)-associated athanogene 1 (BAG-1), which translocates the GR to mitochondria, where it can have diverse effects. Melatonin also suppresses GR nuclear translocation by maintaining the GR in a complex with heat shock protein 90 (Hsp90). Melatonin, directly and/or epigenetically, can upregulate BAG-1, suggesting that the dramatic 10-fold decrease in pineal melatonin from adolescence to the ninth decade of life will attenuate the capacity of night-time melatonin to modulate the effects of the early morning CAR. The interactions of pineal melatonin/BAG-1/Hsp90 with the CAR are proposed to underpin how aging and circadian dysregulation are associated with cancer risk. This may be mediated via differential effects of melatonin/BAG-1/Hsp90/GR in different cells of microenvironments across the body, from which tumors emerge. This provides a model of cancer pathogenesis that better integrates previously disparate bodies of data, including how immune cells are regulated by cancer cells in the tumor microenvironment, at least partly via the cancer cell regulation of the tryptophan-melatonin pathway. This has a number of future research and treatment implications. ,George Anderson [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [178] => Array ( [ArticleId] => 859 [Create_Time] => 2023-10-26 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231026052419.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002177/1002177.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002177/1002177.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002177/1002177_cover.png [JournalsId] => 4 [Title] => A review on in silico virtual screening methods in COVID-19 using anticancer drugs and other natural/chemical inhibitors [Abstract] => The present coronavirus disease 2019 (COVID-19) pandemic scenario has posed a difficulty for cancer treatment. Even under ideal conditions, malignancies like small cell lung cancer (SCLC) are challe [AbstractComplete] =>The present coronavirus disease 2019 (COVID-19) pandemic scenario has posed a difficulty for cancer treatment. Even under ideal conditions, malignancies like small cell lung cancer (SCLC) are challenging to treat because of their fast development and early metastases. The treatment of these patients must not be jeopardized, and they must be protected as much as possible from the continuous spread of the COVID-19 infection. Initially identified in December 2019 in Wuhan, China, the contagious coronavirus illness 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Finding inhibitors against the druggable targets of SARS-CoV-2 has been a significant focus of research efforts across the globe. The primary motivation for using molecular modeling tools against SARS-CoV-2 was to identify candidates for use as therapeutic targets from a pharmacological database. In the published study, scientists used a combination of medication repurposing and virtual drug screening methodologies to target many structures of SARS-CoV-2. This virus plays an essential part in the maturation and replication of other viruses. In addition, the total binding free energy and molecular dynamics (MD) modeling findings showed that the dynamics of various medications and substances were stable; some of them have been tested experimentally against SARS-CoV-2. Different virtual screening (VS) methods have been discussed as potential means by which the evaluated medications that show strong binding to the active site might be repurposed for use against SARS-CoV-2.
[Names] => Babak Sokouti [Doi] => 10.37349/etat.2023.00177 [Published] => October 26, 2023 [Viewed] => 627 [Downloaded] => 22 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00177 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:994–1026 [Recommend] => 0 [Keywords] => Virtual screening, coronavirus disease 2019, cancer, severe acute respiratory syndrome coronavirus 2, molecular dynamics, docking, repurposing [DetailTitle] => [DetailUrl] => [Id] => 1002177 [ris] => https://www.explorationpub.com/uploads/Article/A1002177/bc87bb688c0da3ba2a91b906d08c348b.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002177/2f7c05e8fc6ddbe7388f4b3c893a64f9.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Sokouti B. A review on in silico virtual screening methods in COVID-19 using anticancer drugs and other natural/chemical inhibitors. 2023;4:994–1026. https://doi.org/10.37349/etat.2023.00177 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-10-22 01:35:07 [Bib_Time] => 2023-10-22 01:35:07 [KeysWordContens] => A review on in silico virtual screening methods in COVID-19 using anticancer drugs and other natural/chemical inhibitors, Virtual screening, coronavirus disease 2019, cancer, severe acute respiratory syndrome coronavirus 2, molecular dynamics, docking, repurposing, The present coronavirus disease 2019 (COVID-19) pandemic scenario has posed a difficulty for cancer treatment. Even under ideal conditions, malignancies like small cell lung cancer (SCLC) are challenging to treat because of their fast development and early metastases. The treatment of these patients must not be jeopardized, and they must be protected as much as possible from the continuous spread of the COVID-19 infection. Initially identified in December 2019 in Wuhan, China, the contagious coronavirus illness 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Finding inhibitors against the druggable targets of SARS-CoV-2 has been a significant focus of research efforts across the globe. The primary motivation for using molecular modeling tools against SARS-CoV-2 was to identify candidates for use as therapeutic targets from a pharmacological database. In the published study, scientists used a combination of medication repurposing and virtual drug screening methodologies to target many structures of SARS-CoV-2. This virus plays an essential part in the maturation and replication of other viruses. In addition, the total binding free energy and molecular dynamics (MD) modeling findings showed that the dynamics of various medications and substances were stable; some of them have been tested experimentally against SARS-CoV-2. Different virtual screening (VS) methods have been discussed as potential means by which the evaluated medications that show strong binding to the active site might be repurposed for use against SARS-CoV-2. ,Babak Sokouti [PublishedText] => Published [IsEdit] => 0 [AccountId] => 57 [Zh] => 1 ) [179] => Array ( [ArticleId] => 860 [Create_Time] => 2023-10-26 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231026061823.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002178/1002178.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002178/1002178.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002178/1002178-cover.png [JournalsId] => 4 [Title] => Integration of signaling pathway and bromodomain and extra-terminal domain inhibition for the treatment of mutant Kirsten rat sarcoma viral oncogene homolog cancer [Abstract] => Mutant Kirsten rat sarcoma viral oncogene homolog (KRAS) is now a drugable oncogenic driver and the KRAS G12C variant responds clinically to sotorasib and adagrasib that covalently block the cystein [AbstractComplete] =>Mutant Kirsten rat sarcoma viral oncogene homolog (KRAS) is now a drugable oncogenic driver and the KRAS G12C variant responds clinically to sotorasib and adagrasib that covalently block the cysteine of the active center and inhibit downstream signaling and proliferation. Unfortunately, progression-free survival (PFS) of lung cancer patients is only 5–6 months and no survival advantage has been found for sotorasib in comparison to docetaxel chemotherapy. Increased responses to KRAS inhibitors are tested in combination with the son of sevenless 1 (SOS1) inhibitors, upstream and downstream signaling modulators as well as chemotherapeutics. Some of these approaches are limited by toxicity to normal tissues and by diverse mechanisms of resistance. In essence, most of these attempts are directed to the inhibition of proliferation by impairment of the signal transduction pathways. The final target of KRAS-mediated growth stimulation is MYC in the cell nucleus that stimulates transcription of a host of genes. In detail, MYC alters genomic enhancer and super-enhancers of transcription that are frequently deregulated in cancer. Such enhancers can be targeted by bromodomain and extra-terminal (BET) inhibitors (BETi) or degraders and this review discusses whether integrated SOS1 inhibition and BET targeting of MYC synergizes against mutant KRAS tumor growth. BET degraders in the form of proteolysis-targeting chimeras (PROTACs) combined with BAY-293-mediated SOS1 inhibition revealed marked cytotoxic synergy against mutant KRAS cancer cells and may constitute a promising option for clinical treatment.
[Names] => Gerhard Hamilton ... Barbara Rath [Doi] => 10.37349/etat.2023.00178 [Published] => October 26, 2023 [Viewed] => 813 [Downloaded] => 19 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00178 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 126 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:1027–1038 [Recommend] => 0 [Keywords] => Non-small cell lung cancer, Kirsten rat sarcoma viral oncogene homolog, son of sevenless 1, bromodomain and extra-terminal inhibitors, proteolysis-targeting chimeras [DetailTitle] => Integrated Approaches for Non-Small-Cell Lung Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/126 [Id] => 1002178 [ris] => https://www.explorationpub.com/uploads/Article/A1002178/558b216200e3fdca82dc1dc12c2114b7.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002178/96b46f607e18bca9b1229d112bdb0be5.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Hamilton G, Stickler S, Rath B. Integration of signaling pathway and bromodomain and extra-terminal domain inhibition for the treatment of mutant Kirsten rat sarcoma viral oncogene homolog cancer. Explor Target Antitumor Ther. 2023;4:1027–38. https://doi.org/10.37349/etat.2023.00178 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-10-23 03:26:14 [Bib_Time] => 2023-10-23 01:55:48 [KeysWordContens] => Integration of signaling pathway and bromodomain and extra-terminal domain inhibition for the treatment of mutant Kirsten rat sarcoma viral oncogene homolog cancer, Non-small cell lung cancer, Kirsten rat sarcoma viral oncogene homolog, son of sevenless 1, bromodomain and extra-terminal inhibitors, proteolysis-targeting chimeras, Mutant Kirsten rat sarcoma viral oncogene homolog (KRAS) is now a drugable oncogenic driver and the KRAS G12C variant responds clinically to sotorasib and adagrasib that covalently block the cysteine of the active center and inhibit downstream signaling and proliferation. Unfortunately, progression-free survival (PFS) of lung cancer patients is only 5–6 months and no survival advantage has been found for sotorasib in comparison to docetaxel chemotherapy. Increased responses to KRAS inhibitors are tested in combination with the son of sevenless 1 (SOS1) inhibitors, upstream and downstream signaling modulators as well as chemotherapeutics. Some of these approaches are limited by toxicity to normal tissues and by diverse mechanisms of resistance. In essence, most of these attempts are directed to the inhibition of proliferation by impairment of the signal transduction pathways. The final target of KRAS-mediated growth stimulation is MYC in the cell nucleus that stimulates transcription of a host of genes. In detail, MYC alters genomic enhancer and super-enhancers of transcription that are frequently deregulated in cancer. Such enhancers can be targeted by bromodomain and extra-terminal (BET) inhibitors (BETi) or degraders and this review discusses whether integrated SOS1 inhibition and BET targeting of MYC synergizes against mutant KRAS tumor growth. BET degraders in the form of proteolysis-targeting chimeras (PROTACs) combined with BAY-293-mediated SOS1 inhibition revealed marked cytotoxic synergy against mutant KRAS cancer cells and may constitute a promising option for clinical treatment. ,Gerhard Hamilton ... Barbara Rath [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [180] => Array ( [ArticleId] => 864 [Create_Time] => 2023-10-26 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231026074629.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002179/1002179.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002179/1002179.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002179/1002179_cover.png [JournalsId] => 4 [Title] => Effect of coronavirus disease 2019 on diagnosis and treatment of hepatocellular carcinoma: a systematic review [Abstract] => Aim: Changes in strategies in the coronavirus disease 2019 (COVID-19) crisis and the imposing of restrictions have isolated many vulnerable patients including those with hepatocellular carcinoma [AbstractComplete] =>Changes in strategies in the coronavirus disease 2019 (COVID-19) crisis and the imposing of restrictions have isolated many vulnerable patients including those with hepatocellular carcinoma (HCC) from routine medical care. This study investigated how the COVID-19 pandemic is affecting the diagnosis and treatment of HCC.
An extensive search was conducted in the PubMed, Scopus, and Web of Science databases by using the appropriate keywords: COVID-19, hepatocellular carcinoma, hepatocellular cancer, and MeSH. Studies in English related to the purpose of the study were included in the analysis, and review studies, case reports, letters to editors, comments, and reports were excluded. The quality of the studies was assessed by the “Adapted Newcastle-Ottawa Quality Assessment Scales” checklist. The Endnote X7 software has been used for managing items.
The final qualitative analysis consisted of 27 articles. During the COVID-19 crisis, HCC diagnosis decreased from 20% to 34.13% compared to pre-crisis. The impact of the COVID-19 pandemic on HCC treatment encompasses a wide range of aspects. Generally, delays in treatment for patients with HCC ranged from more than one month for 21.5% of patients in France, to two months for 26% of patients in Italy, up to 30% in Austria, and 66.7% in Asia-Pacific countries.
According to the findings, developing and implementing appropriate diagnostic and therapeutic strategies and developing low-cost and high-precision screening programs among high-risk populations seem to be effective in reducing the impact of the COVID-19 pandemic on HCC management.
This study aimed to establish a learning system using an artificial neural network (ANN) to predict the effects of vitamin D supplementation on the serum levels of vitamin D, inflammatory factors, and total antioxidant capacity (TAC) in women with breast cancer.
The data set of the current project was created from women with breast cancer who were referred to the Shafa State Hospital of Patients with Cancers in Ahvaz city, Iran. Modeling was implemented using the data set at the serum levels of vitamin D, tumor necrosis factor-α (TNF-α), transforming growth factor β (TGF-β), and TAC, before and after vitamin D3 supplement therapy. A prediction ANN model was designed to detect the effects of vitamin D3 supplementation on the serum level changes of vitamin D, inflammatory factors and TAC.
The results showed that the ANN model could predict the effect of vitamin D3 supplementation on the serum level changes of vitamin D, TNF-α, TGF-β1, and TAC with an accuracy average of 85%, 40%, 89.5%, and 88.1%, respectively.
According to the findings of the study, the ANN method could accurately predict the effect of vitamin D3 supplementation on the serum levels of vitamin D, TNF-α, TGF-β1, and TAC. The results showed that the proposed ANN method can help specialists to improve the treatment process more confidently in terms of time and accuracy of predicting the influence of vitamin D supplementation on the factors affecting the progression of breast cancer (https://www.irct.ir/ identifier: IRCT2015090623924N1).
Alternative protein-protein interactions (PPIs) arising from mutations or post-translational modifications (PTMs), termed phenotypic switching (PS), are critical for the transmission of alternative pathogenic signals and are particularly significant in cancer. In recent years, PPIs have emerged as promising targets for rational drug design, primarily because their high specificity facilitates targeting of disease-related signaling pathways. However, obstacles exist at the molecular level that arise from the properties of the interaction interfaces and the propensity of small molecule drugs to interact with more than one cleft surface. The difficulty in identifying small molecules that act as activators or inhibitors to counteract the biological effects of mutations raises issues that have not been encountered before. For example, small molecules can bind tightly but may not act as drugs or bind to multiple sites (interaction promiscuity). Another reason is the absence of significant clefts on protein surfaces; if a pocket is present, it may be too small, or its geometry may prevent binding. PS, which arises from oncogenic (alternative) signaling, causes drug resistance and forms the basis for the systemic robustness of tumors. In this review, the properties of PPI interfaces relevant to the design and development of targeting drugs are examined. In addition, the interactions between three tyrosine kinase inhibitors (TKIs) employed as drugs are discussed. Finally, potential novel targets of one of these drugs were identified in silico.
[Names] => Christos Ladias ... Nikolaos A. Papanikolaou [Doi] => 10.37349/etat.2023.00181 [Published] => October 30, 2023 [Viewed] => 544 [Downloaded] => 15 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00181 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 32 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:1071–1081 [Recommend] => 0 [Keywords] => Protein-protein interactions, phenotypic switching, imatinib, ponatinib, ibrutinib [DetailTitle] => Off-label drugs and -omics data in cancer treatment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/32 [Id] => 1002181 [ris] => https://www.explorationpub.com/uploads/Article/A1002181/af29a0f92b6690630276aaec410413ca.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002181/22d870905fcef47d747d10c906ddd6c3.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Ladias C, Papakotoulas P, Papaioannou M, Papanikolaou NA. Overcoming phenotypic switching: targeting protein-protein interactions in cancer. Explor Target Antitumor Ther. 2023;4:1071–81. https://doi.org/10.37349/etat.2023.00181 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-10-27 02:04:39 [Bib_Time] => 2023-10-27 02:04:39 [KeysWordContens] => Overcoming phenotypic switching: targeting protein-protein interactions in cancer, Protein-protein interactions, phenotypic switching, imatinib, ponatinib, ibrutinib, Alternative protein-protein interactions (PPIs) arising from mutations or post-translational modifications (PTMs), termed phenotypic switching (PS), are critical for the transmission of alternative pathogenic signals and are particularly significant in cancer. In recent years, PPIs have emerged as promising targets for rational drug design, primarily because their high specificity facilitates targeting of disease-related signaling pathways. However, obstacles exist at the molecular level that arise from the properties of the interaction interfaces and the propensity of small molecule drugs to interact with more than one cleft surface. The difficulty in identifying small molecules that act as activators or inhibitors to counteract the biological effects of mutations raises issues that have not been encountered before. For example, small molecules can bind tightly but may not act as drugs or bind to multiple sites (interaction promiscuity). Another reason is the absence of significant clefts on protein surfaces; if a pocket is present, it may be too small, or its geometry may prevent binding. PS, which arises from oncogenic (alternative) signaling, causes drug resistance and forms the basis for the systemic robustness of tumors. In this review, the properties of PPI interfaces relevant to the design and development of targeting drugs are examined. In addition, the interactions between three tyrosine kinase inhibitors (TKIs) employed as drugs are discussed. Finally, potential novel targets of one of these drugs were identified in silico. ,Christos Ladias ... Nikolaos A. Papanikolaou [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [183] => Array ( [ArticleId] => 898 [Create_Time] => 2023-10-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231031005709.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002182/1002182.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002182/1002182.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002182/1002182-cover.png [JournalsId] => 4 [Title] => Coronavirus disease 2019 and lung cancer: where are we? [Abstract] => Oncology patients are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to hospital contact and an immunological system that can be compromised by antine [AbstractComplete] =>Oncology patients are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to hospital contact and an immunological system that can be compromised by antineoplastic therapy and supportive treatments. Certain similarities have been described in the physiopathology of coronavirus disease 2019 (COVID-19) and lung cancer (LC) that may explain the higher probability of these patients of developing a more serious disease with more frequent hospitalizations and even death, especially with the addition of smoking, cardiovascular and respiratory comorbidities, old age and corticosteroids use. Pre-existing lesions and cancer therapies change the normal architecture of the lungs, so diagnostic scales such as COVID-19 Reporting and Data System (CO-RADS) are of vital importance for a correct diagnosis and patient homogenization, with a high inter-observer correlation. Moreover, anticancer treatments have required an adaptation to reduce the number of visits to the hospital [hypofractionated radiotherapy (RT), larger intervals between chemotherapy cycles, delay in follow-up tests, among others]. In a way, this has also caused a delay in the diagnosis of new cancers. On the other hand, vaccination has had a positive impact on the mortality of these patients, who maintain a similar seroprevalence to the rest of the population, with a similar impact in mortality.
[Names] => Abrahams Ocanto ... Felipe Couñago [Doi] => 10.37349/etat.2023.00182 [Published] => October 30, 2023 [Viewed] => 720 [Downloaded] => 10 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00182 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 43 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:1082–1094 [Recommend] => 0 [Keywords] => Coronavirus disease 2019, lung cancer, radiotherapy [DetailTitle] => COVID-19 and Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/43 [Id] => 1002182 [ris] => https://www.explorationpub.com/uploads/Article/A1002182/e0c82b822909161e0219ba1acbdd4dd9.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002182/5d556df5929cd01061bd9f08a93323bf.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Ocanto A, Mielgo-Rubio X, Luna Tirado J, Linares Mesa N, López Valcárcel M, Pedraza S, et al. Coronavirus disease 2019 and lung cancer: where are we? Explor Target Antitumor Ther. 2023;4:1082–94. https://doi.org/10.37349/etat.2023.00182 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-10-27 02:14:04 [Bib_Time] => 2023-10-27 02:14:04 [KeysWordContens] => Coronavirus disease 2019 and lung cancer: where are we?, Coronavirus disease 2019, lung cancer, radiotherapy, Oncology patients are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to hospital contact and an immunological system that can be compromised by antineoplastic therapy and supportive treatments. Certain similarities have been described in the physiopathology of coronavirus disease 2019 (COVID-19) and lung cancer (LC) that may explain the higher probability of these patients of developing a more serious disease with more frequent hospitalizations and even death, especially with the addition of smoking, cardiovascular and respiratory comorbidities, old age and corticosteroids use. Pre-existing lesions and cancer therapies change the normal architecture of the lungs, so diagnostic scales such as COVID-19 Reporting and Data System (CO-RADS) are of vital importance for a correct diagnosis and patient homogenization, with a high inter-observer correlation. Moreover, anticancer treatments have required an adaptation to reduce the number of visits to the hospital [hypofractionated radiotherapy (RT), larger intervals between chemotherapy cycles, delay in follow-up tests, among others]. In a way, this has also caused a delay in the diagnosis of new cancers. On the other hand, vaccination has had a positive impact on the mortality of these patients, who maintain a similar seroprevalence to the rest of the population, with a similar impact in mortality. ,Abrahams Ocanto ... Felipe Couñago [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [184] => Array ( [ArticleId] => 899 [Create_Time] => 2023-10-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231031005828.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002183/1002183.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002183/1002183.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002183/1002183-cover.png [JournalsId] => 4 [Title] => Impact of coronavirus disease 2019 pandemic on good clinical practice trials in oncology [Abstract] => Aim: Coronavirus disease 2019 (COVID-19) became pandemic on 11th March 2020 and it deeply stressed the healthcare system. Cancer patients represent a vulnerable population, so many recommendation [AbstractComplete] =>Coronavirus disease 2019 (COVID-19) became pandemic on 11th March 2020 and it deeply stressed the healthcare system. Cancer patients represent a vulnerable population, so many recommendations have been approved to ensure optimal management. Clinical research was notably impacted by COVID too. This review aims to analyze the challenges occurred during a pandemic for the management of enrolled patients (enrollment, use of telemedicine visits, study procedures) and for the clinical trials system (from feasibility to selection visit, site initiation visit, monitorings, use of e-signature, deviations and discontinuations).
The studies included in the present review were selected from PubMed/Google Scholar/ScienceDirect databases.
During the first phase of pandemic many clinical trials were suspended in accrual and, as the pandemic progressed, recommendations were established to guarantee the safety and the continuity of care of enrolled patients. In addition, lot of new strategies was found during the pandemic to reduce the negative consequences on clinical trial performance and to guarantee new opportunities of care in the respect of good clinical practice (GCP) in a bad scenario.
Among all modifiers, investigators would prefer to maintain the positive ones such as pragmatic and simplified trial designs and protocols, reducing in-person visits when not necessary and to minimizing sponsor and contract research organizations (CROs) visits.
Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide with a survival rate below fifty percent. Addressing meager therapeutic options, a series of small molecule inhibitors were screened for antitumor efficacy. The most potent analog, acryl-3,5-bis(2,4-difluorobenzylidene)-4-piperidone (DiFiD; A-DiFiD), demonstrated strong cellular JUN proto-oncogene, activator protein 1 (AP-1) transcription factor subunit (JUN, c-Jun) antagonism. c-Jun, an oncogenic transcription factor, promotes cancer progression, invasion, and adhesion; high (JUN) mRNA expression correlates with poorer HNSCC survival.
Four new small molecules were generated for cytotoxicity screening in HNSCC cell lines. A-DiFiD-treated HNSCC cells were assessed for cytotoxicity, colony formation, invasion, migration, and adhesion. Dot blot array was used to identify targets. Phospho-c-Jun (p-c-Jun) expression was analyzed using immunoblotting. The Cancer Genome Atlas (TCGA) head and neck cancer datasets were utilized to determine overall patient survival. The Clinical Proteomic Tumor Analysis Consortium (CPTAC) datasets interfaced with University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) were analyzed to determine protein levels of c-Jun in HNSCC patients and correlate levels with patient.
Of the small molecules tested, A-DiFiD was the most potent in HNSCC lines, while demonstrating low half-maximal drug inhibitory concentration (IC50) in non-malignant Het-1A cells. Additionally, A-DiFiD abrogated cell invasion, migration, and colony formation. Phospho-kinase in vitro array demonstrated A-DiFiD reduced p-c-Jun. Likewise, a time dependent reduction in p-c-Jun was observed starting at 3 min post A-DiFiD treatment. TCGA Firehose Legacy vs. recurrent and metastatic head and neck cancer reveal a nearly 3% DNA amplification in recurrent/metastatic tumor compared to below 1% in primary tumors that had no lymph node metastasis. CPTAC analysis show higher tumor c-Jun levels compared to normal. Patients with high JUN expression had significantly reduced 3-year survival.
A-DiFiD targets c-Jun, a clinical HNSCC driver, with potent anti-tumor effects.
Many human cancers carry missense mutations in or deletions of the tumor protein 53 (TP53) tumor suppressor gene. TP53’s product, p53 regulates many biological processes, including cell metabolism. Cholesterol is a key lipid needed for the maintenance of membrane function and tissue homeostasis while also serving as a precursor for steroid hormone and bile acid synthesis. An over-abundance of cholesterol can lead to its esterification and storage as cholesterol esters. The recent study has shown that the loss of p53 leads to excessive cholesterol ester biosynthesis, which promotes hepatocellular carcinoma in mice. Blocking cholesterol esterification improves treatment outcomes, particularly for liver cancers with p53 deletions/mutations that originate in a background of non-alcoholic fatty liver disease.
[Names] => Youjun Li ... Edward V. Prochownik [Doi] => 10.37349/etat.2023.00185 [Published] => October 31, 2023 [Viewed] => 753 [Downloaded] => 21 [Subject] => Perspective [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00185 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 113 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:1122–1127 [Recommend] => 0 [Keywords] => Hepatocellular carcinoma, p53 tumor suppressor, mevalonate pathway, cholesterol esterification, sterol O-acyltransferase 1 [DetailTitle] => Therapeutic Targeting of the Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/113 [Id] => 1002185 [ris] => https://www.explorationpub.com/uploads/Article/A1002185/d5b41ebd4a2c2ef2c0fe2c9764b39d11.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002185/10c943d61729d744b8721385277b0d9f.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Li Y, Karin M, Prochownik EV. Cholesterol esterification and p53-mediated tumor suppression. Explor Target Antitumor Ther. 2023;4:1122–7. https://doi.org/10.37349/etat.2023.00185 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-11-01 02:23:14 [Bib_Time] => 2023-11-01 02:23:14 [KeysWordContens] => Cholesterol esterification and p53-mediated tumor suppression, Hepatocellular carcinoma, p53 tumor suppressor, mevalonate pathway, cholesterol esterification, sterol O-acyltransferase 1, Many human cancers carry missense mutations in or deletions of the tumor protein 53 (TP53) tumor suppressor gene. TP53’s product, p53 regulates many biological processes, including cell metabolism. Cholesterol is a key lipid needed for the maintenance of membrane function and tissue homeostasis while also serving as a precursor for steroid hormone and bile acid synthesis. An over-abundance of cholesterol can lead to its esterification and storage as cholesterol esters. The recent study has shown that the loss of p53 leads to excessive cholesterol ester biosynthesis, which promotes hepatocellular carcinoma in mice. Blocking cholesterol esterification improves treatment outcomes, particularly for liver cancers with p53 deletions/mutations that originate in a background of non-alcoholic fatty liver disease. ,Youjun Li ... Edward V. Prochownik [PublishedText] => Published [IsEdit] => 0 [AccountId] => 77 [Zh] => 1 ) [187] => Array ( [ArticleId] => 924 [Create_Time] => 2023-11-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202401/20240105081207.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002186/1002186.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002186/1002186.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002186/1002186_cover.png [JournalsId] => 4 [Title] => A decade of CD4+ chimeric antigen receptor T-cell evolution in two chronic lymphocytic leukemia patients: were chronic lymphocytic leukemia cells present? [Abstract] => On Feb 2, 2022, Nature published the paper titled “Decade-long leukemia remissions with the persistence of CD4+ CAR T-cells” (Nature. 2022;602:503–9. doi: 10.1038/s41586-021-04390-6). Accordin [AbstractComplete] =>On Feb 2, 2022, Nature published the paper titled “Decade-long leukemia remissions with the persistence of CD4+ CAR T-cells” (Nature. 2022;602:503–9. doi: 10.1038/s41586-021-04390-6). According to the results presented, it could be argued that “chimeric antigen receptor (CAR) T-cells can actually cure patients with chronic lymphocytic leukemia (CLL)”. CAR T-cells remained detectable more than ten years after infusion, and immunoglobulin heavy chain (IGH) rearrangement deep sequencing showed persistent deep molecular remission for both patients (no CLL clonotypes were detectable six months after CAR T-cell infusion and onwards). However, the existing actual disease status of both patients remained unclear, as it was unknown: (1) if CAR T-cells killed all leukemia cells during the initial anti-leukemic response phase, that is, soon after CAR T-cell infusion into both patients; (2) if few CLL cells survived, but persistent CAR T-cells had been able to destroy any leukemia cells before they reach detectable levels. In the first case, both patients could be considered definitely cured; in the second not and their decade-prolonged deep remission could be a consequence of the cytotoxic activity of the functionally active CD4+ CAR T-cells. The first version appears to be stronger and the supporting arguments have been included in a comprehensive commentary article. A new therapeutic intervention may emerge with the potential to fully improve the quality of life of both patients and in addition, ongoing research into CAR T-cells may turn in a new, more effective direction.
[Names] => Dimitrios Bouzianas, Stella Bouziana [Doi] => 10.37349/etat.2023.00186 [Published] => October 31, 2023 [Viewed] => 768 [Downloaded] => 18 [Subject] => Commentary [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00186 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 175 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:1128–1135 [Recommend] => 0 [Keywords] => Chimeric antigen receptor T-cells, chronic lymphocytic leukemia, immunotherapy, long-term remission, CD4+/CD8+ T-lymphocytes [DetailTitle] => Novel Strategies and Targets for Immunotherapy of Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/175 [Id] => 1002186 [ris] => https://www.explorationpub.com/uploads/Article/A1002186/c3ce52f3067c7d3b1bffde6f2bfb5f4b.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002186/986d66f33911cd46877226f245529a95.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Bouzianas D, Bouziana S. A decade of CD4+ chimeric antigen receptor T-cell evolution in two chronic lymphocytic leukemia patients: were chronic lymphocytic leukemia cells present? Explor Target Antitumor Ther. 2023;4:1128–35. https://doi.org/10.37349/etat.2023.00186 [Jindex] => 0 [CName] => DimitriosBouzianas, [CEmail] => dimbou55@gmail.com, [Ris_Time] => 2023-10-31 04:00:53 [Bib_Time] => 2023-10-31 03:51:52 [KeysWordContens] => A decade of CD4+ chimeric antigen receptor T-cell evolution in two chronic lymphocytic leukemia patients: were chronic lymphocytic leukemia cells present?, Chimeric antigen receptor T-cells, chronic lymphocytic leukemia, immunotherapy, long-term remission, CD4+/CD8+ T-lymphocytes, On Feb 2, 2022, Nature published the paper titled “Decade-long leukemia remissions with the persistence of CD4+ CAR T-cells” (Nature. 2022;602:503–9. doi: 10.1038/s41586-021-04390-6). According to the results presented, it could be argued that “chimeric antigen receptor (CAR) T-cells can actually cure patients with chronic lymphocytic leukemia (CLL)”. CAR T-cells remained detectable more than ten years after infusion, and immunoglobulin heavy chain (IGH) rearrangement deep sequencing showed persistent deep molecular remission for both patients (no CLL clonotypes were detectable six months after CAR T-cell infusion and onwards). However, the existing actual disease status of both patients remained unclear, as it was unknown: (1) if CAR T-cells killed all leukemia cells during the initial anti-leukemic response phase, that is, soon after CAR T-cell infusion into both patients; (2) if few CLL cells survived, but persistent CAR T-cells had been able to destroy any leukemia cells before they reach detectable levels. In the first case, both patients could be considered definitely cured; in the second not and their decade-prolonged deep remission could be a consequence of the cytotoxic activity of the functionally active CD4+ CAR T-cells. The first version appears to be stronger and the supporting arguments have been included in a comprehensive commentary article. A new therapeutic intervention may emerge with the potential to fully improve the quality of life of both patients and in addition, ongoing research into CAR T-cells may turn in a new, more effective direction. ,Dimitrios Bouzianas, Stella Bouziana [PublishedText] => Published [IsEdit] => 0 [AccountId] => 87 [Zh] => 1 ) [188] => Array ( [ArticleId] => 951 [Create_Time] => 2023-12-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202312/20231201005932.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002187/1002187.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002187/1002187.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002187/1002187_cover.png [JournalsId] => 4 [Title] => Comparing efficacy and safety of upfront treatment strategies for anaplastic lymphoma kinase-positive non-small cell lung cancer: a network meta-analysis [Abstract] => Aim: This article is based on our previous research, which was presented as a post at the Congress Aiom 2022 Congress and published in Tumori Journal as Conference Abstract (Tumori J. 2022;108:1 [AbstractComplete] =>This article is based on our previous research, which was presented as a post at the Congress Aiom 2022 Congress and published in Tumori Journal as Conference Abstract (Tumori J. 2022;108:1–194. doi: 10.1177/03008916221114500). In this paper, a comprehensive presentation of all the achieved results is provided. Several tyrosine kinase inhibitors (TKIs) have been investigated to treat patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). However, direct comparisons between these TKIs are lacking, with many only being compared to crizotinib. To address this gap, a network meta-analysis was conducted to compare the efficacy and safety of various first-line systemic therapies for ALK-positive NSCLC.
A thorough search of PubMed, Embase, and Cochrane Library was performed to identify randomized controlled trials (RCTs) published between January 01, 2000 and April 01, 2022, and included trials that investigated upfront treatments for this molecular subgroup and reported overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) of grade 3 or higher (grade ≥ 3 AEs).
The analysis included 9 RCTs with 2,443 patients receiving eight different treatments: alectinib (at two different dosages), brigatinib, ceritinib, crizotinib, ensartinib, lorlatinib, and chemotherapy. Second and third-generation TKIs significantly prolonged PFS compared to crizotinib, with lorlatinib having the highest probability of yielding the most favorable PFS, followed by alectinib (300 mg or 600 mg). However, only alectinib has been shown to significantly prolong OS compared to crizotinib to date. Lorlatinib appears superior in reducing the risk of central nervous system (CNS) progression, followed by alectinib 600 mg. Ceritinib had the highest rate of AEs, followed by lorlatinib and brigatinib.
Based on the network meta-analysis, alectinib and lorlatinib emerged as the most promising upfront treatment options. These treatments provide prolonged disease control while maintaining an acceptable safety profile.
The present study aims to generate chimeric mouse single-chain variable fragment (scFv) and immunoglobulin G1 (IgG1) crystallizable fragment (Fc) antibody against disialoganglioside (GD2) for the treatment of neuroblastoma (NB). The generated scFv-IgG Fc antibody, lacking first constant domain of heavy chain (CH1), is of a smaller size than the natural antibody and has anti-tumor activity.
Vector for scFv-IgG Fc antibody was constructed and scFv-IgG Fc antibody was expressed in human embryonic kidney 293T (HEK293T) cell line. Purification of scFv-IgG Fc antibody from the culture supernatant of transfected HEK293T cells was performed by Protein G affinity chromatography. The structure and binding activity of scFv-IgG Fc antibody were verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), western blotting (WB), and immunofluorescence techniques. Anti-tumor activities by antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) were determined.
Using plasmid fusion-human IgG1-Fc2 tag vector (pFUSE-hIgG1-Fc2), a plasmid vector encoding chimeric mouse scFv and hIgG1 Fc antibody against GD2 was successfully constructed. This vector was transfected into human HEK293T cells to produce scFv-IgG Fc antibody. The transfected HEK293T cells could produce chimeric scFv-IgG Fc antibody against GD2, which lacks the IgG heavy chain CH1 domain but carries CH2 and CH3 domains. The chimeric antibodies could be purified from the culture supernatant of the transfected HEK293T culture in the presence of zeocin drug. The produced GD2 scFv-IgG Fc antibodies, which are smaller in size than the intact antibody, could trigger the killing of GD2 expressed NB cell line SH-SY5Y by ADCC and ADCP mechanisms.
The results indicate that chimeric scFv-hIgG Fc antibody, lacking heavy chain CH1 domain, could mediate antibody induced anti-tumor activities. The small size of this type of chimeric antibody may be employed as anti-GD2 antibody for NB therapy.
Early clinical trials aimed to halt cancer progression by inhibiting the growth of new blood vessels in tumors through single-agent targeted therapy with bevacizumab. These trials largely proved unsuccessful. However, bevacizumab turned out to be efficient when administered in combination with other anticancer drugs. The efficacy of this approach is explained by the ability of bevacizumab to eliminate immature blood vessels thus normalizing intratumoral blood flow and improving the delivery of cytotoxic or targeted agents. This report describes four cases of heavily pretreated patients with metastatic HER2-positive breast cancer, who had no meaningful treatment options left, and who received single-agent bevacizumab as an empirical last-resort therapy. Three of these patients had severe complaints, and they demonstrated striking symptomatic relief within the first day of this treatment. In addition to the observed “Lazarus response”, which was likely attributed to the bevacizumab-driven resolution of edema, some evidence of a direct antitumor effect was observed. These data may call for the reconsideration of bevacizumab monotherapy in patients with HER2-associated breast cancer, and perhaps in some other categories of cancer patients.
[Names] => Alexey V. Emshanov ... Evgeny N. Imyanitov [Doi] => 10.37349/etat.2023.00189 [Published] => December 06, 2023 [Viewed] => 494 [Downloaded] => 17 [Subject] => Case Report [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00189 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:1157–1164 [Recommend] => 0 [Keywords] => Bevacizumab, breast cancer, edema, HER2, single-agent therapy [DetailTitle] => [DetailUrl] => [Id] => 1002189 [ris] => https://www.explorationpub.com/uploads/Article/A1002189/b92b2a340e9eeabd88ef98c4586af3f7.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002189/dac3657a9c06a161e2b241eb08023625.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Emshanov AV, Nesterov DV, Sokolova TN, Amankwah PS, Imyanitov EN. Unexpected “Lazarus response” to single-agent bevacizumab in heavily pretreated patients with HER2-positive breast cancer. Explor Target Antitumor Ther. 2023;4:1157–64. https://doi.org/10.37349/etat.2023.00189 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-12-01 02:54:07 [Bib_Time] => 2023-12-01 02:54:07 [KeysWordContens] => Unexpected “Lazarus response” to single-agent bevacizumab in heavily pretreated patients with HER2-positive breast cancer, Bevacizumab, breast cancer, edema, HER2, single-agent therapy, Early clinical trials aimed to halt cancer progression by inhibiting the growth of new blood vessels in tumors through single-agent targeted therapy with bevacizumab. These trials largely proved unsuccessful. However, bevacizumab turned out to be efficient when administered in combination with other anticancer drugs. The efficacy of this approach is explained by the ability of bevacizumab to eliminate immature blood vessels thus normalizing intratumoral blood flow and improving the delivery of cytotoxic or targeted agents. This report describes four cases of heavily pretreated patients with metastatic HER2-positive breast cancer, who had no meaningful treatment options left, and who received single-agent bevacizumab as an empirical last-resort therapy. Three of these patients had severe complaints, and they demonstrated striking symptomatic relief within the first day of this treatment. In addition to the observed “Lazarus response”, which was likely attributed to the bevacizumab-driven resolution of edema, some evidence of a direct antitumor effect was observed. These data may call for the reconsideration of bevacizumab monotherapy in patients with HER2-associated breast cancer, and perhaps in some other categories of cancer patients. ,Alexey V. Emshanov ... Evgeny N. Imyanitov [PublishedText] => Published [IsEdit] => 0 [AccountId] => 87 [Zh] => 1 ) [191] => Array ( [ArticleId] => 963 [Create_Time] => 2023-12-11 [zipUrl] => https://www.explorationpub.com/uploads/zip/202312/20231211011317.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002190/1002190.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002190/1002190.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002190/1002190-cover.png [JournalsId] => 4 [Title] => Targeting cancer stem cell plasticity in triple-negative breast cancer [Abstract] => Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype with limited treatment options. Cancer stem cells (CSCs) are thought to play a crucial role in TNBC progression and [AbstractComplete] =>Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype with limited treatment options. Cancer stem cells (CSCs) are thought to play a crucial role in TNBC progression and resistance to therapy. CSCs are a small subpopulation of cells within tumors that possess self-renewal and differentiation capabilities and are responsible for tumor initiation, maintenance, and metastasis. CSCs exhibit plasticity, allowing them to switch between states and adapt to changing microenvironments. Targeting CSC plasticity has emerged as a promising strategy for TNBC treatment. This review summarizes recent advances in understanding the molecular mechanisms underlying CSC plasticity in TNBC and discusses potential therapeutic approaches targeting CSC plasticity.
[Names] => Zhengwang Guo, Shuyan Han [Doi] => 10.37349/etat.2023.00190 [Published] => December 11, 2023 [Viewed] => 480 [Downloaded] => 12 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00190 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 137 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:1165–1181 [Recommend] => 0 [Keywords] => Triple-negative breast cancer, cancer stem cell, plasticity, therapeutic targets [DetailTitle] => Innovative Strategies to Target Triple-negative Breast Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/137 [Id] => 1002190 [ris] => https://www.explorationpub.com/uploads/Article/A1002190/b3bc0ec65d4339548fa1ee1661a4ce51.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002190/0e914e6a6f51289244a813725db8bc50.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Guo Z, Han S. Targeting cancer stem cell plasticity in triple-negative breast cancer. Explor Target Antitumor Ther. 2023;4:1165–81. https://doi.org/10.37349/etat.2023.00190 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-11-29 08:45:50 [Bib_Time] => 2023-11-29 08:45:50 [KeysWordContens] => Targeting cancer stem cell plasticity in triple-negative breast cancer, Triple-negative breast cancer, cancer stem cell, plasticity, therapeutic targets, Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype with limited treatment options. Cancer stem cells (CSCs) are thought to play a crucial role in TNBC progression and resistance to therapy. CSCs are a small subpopulation of cells within tumors that possess self-renewal and differentiation capabilities and are responsible for tumor initiation, maintenance, and metastasis. CSCs exhibit plasticity, allowing them to switch between states and adapt to changing microenvironments. Targeting CSC plasticity has emerged as a promising strategy for TNBC treatment. This review summarizes recent advances in understanding the molecular mechanisms underlying CSC plasticity in TNBC and discusses potential therapeutic approaches targeting CSC plasticity. ,Zhengwang Guo, Shuyan Han [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [192] => Array ( [ArticleId] => 983 [Create_Time] => 2023-12-13 [zipUrl] => https://www.explorationpub.com/uploads/zip/202312/20231213061641.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002191/1002191.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002191/1002191.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002191/1002191_cover.png [JournalsId] => 4 [Title] => Is oligoprogression a potentially curable disease in epidermal growth factor receptor mutant lung adenocarcinoma? [Abstract] => Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have shown impressive results in EGFR mutant lung cancer (LC) patients in terms of disease control rate wit [AbstractComplete] =>Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have shown impressive results in EGFR mutant lung cancer (LC) patients in terms of disease control rate with a positive impact on overall survival. Nevertheless, after months of treatment with targeted therapy, progression inevitably occurs. Some patients develop oligoprogression and local treatment is required for optimal disease control while maintaining EGFR-TKIs. This work features a clinical case of a patient harboring an EGFR mutant LC undergoing oligoprogression to EGFR-TKIs, first into the brain and afterward to the primary tumor, requiring local ablative strategies, including primary tumor resection three years after the start of osimertinib. Currently, the patient is still alive and continues with a complete response upon EGFR-TKIs maintenance. Hence, oligoprogression, even in driven oncogenic tumors, represents a distinct biological entity and potential curative disease that deserves particular consideration in multidisciplinary tumor boards. In this case, tumor primary resection after three years of the initial diagnosis represents a paradigm shift in the treatment of EGFR mutant patients.
[Names] => Sviatoslav Chekhun ... Maria Saigí [Doi] => 10.37349/etat.2023.00191 [Published] => December 13, 2023 [Viewed] => 972 [Downloaded] => 15 [Subject] => Case Report [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00191 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:1182–1187 [Recommend] => 0 [Keywords] => Lung adenocarcinoma, epidermal growth factor receptor, oligoprogression, targeted therapy, epidermal growth factor receptor-tyrosine kinase inhibitors [DetailTitle] => [DetailUrl] => [Id] => 1002191 [ris] => https://www.explorationpub.com/uploads/Article/A1002191/087253fd1c7a36fc56d4a37ff1da8cc5.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002191/9fd31e28791fcd62193361f918219ab3.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Chekhun S, Lopez-Paradís A, Urbizu A, Morán T, Mañes A, Cucurull M, et al. Is oligoprogression a potentially curable disease in epidermal growth factor receptor mutant lung adenocarcinoma? Explor Target Antitumor Ther. 2023;4:1182–7. https://doi.org/10.37349/etat.2023.00191 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-12-13 06:16:42 [Bib_Time] => 2023-12-13 06:16:42 [KeysWordContens] => Is oligoprogression a potentially curable disease in epidermal growth factor receptor mutant lung adenocarcinoma?, Lung adenocarcinoma, epidermal growth factor receptor, oligoprogression, targeted therapy, epidermal growth factor receptor-tyrosine kinase inhibitors, Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have shown impressive results in EGFR mutant lung cancer (LC) patients in terms of disease control rate with a positive impact on overall survival. Nevertheless, after months of treatment with targeted therapy, progression inevitably occurs. Some patients develop oligoprogression and local treatment is required for optimal disease control while maintaining EGFR-TKIs. This work features a clinical case of a patient harboring an EGFR mutant LC undergoing oligoprogression to EGFR-TKIs, first into the brain and afterward to the primary tumor, requiring local ablative strategies, including primary tumor resection three years after the start of osimertinib. Currently, the patient is still alive and continues with a complete response upon EGFR-TKIs maintenance. Hence, oligoprogression, even in driven oncogenic tumors, represents a distinct biological entity and potential curative disease that deserves particular consideration in multidisciplinary tumor boards. In this case, tumor primary resection after three years of the initial diagnosis represents a paradigm shift in the treatment of EGFR mutant patients. ,Sviatoslav Chekhun ... Maria Saigí [PublishedText] => Published [IsEdit] => 0 [AccountId] => 77 [Zh] => 1 ) [193] => Array ( [ArticleId] => 1004 [Create_Time] => 2023-12-21 [zipUrl] => https://www.explorationpub.com/uploads/zip/202312/20231229055338.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002192/1002192.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002192/1002192.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002192/1002192_cover.png [JournalsId] => 4 [Title] => Receptor tyrosine kinase-like orphan receptor 1 inhibitor strictinin exhibits anti-cancer properties against highly aggressive androgen-independent prostate cancer [Abstract] => Aim: It is important to identify anti-cancer compounds that can inhibit specific molecular targets to eradicate androgen-receptor negative (ARneg), androgen-independent (AI) prostate cancer, whic [AbstractComplete] =>It is important to identify anti-cancer compounds that can inhibit specific molecular targets to eradicate androgen-receptor negative (ARneg), androgen-independent (AI) prostate cancer, which is an aggressive form of prostate cancer with limited treatment options. The goal of this study was to selectively target prostate cancer cells that have high levels of oncogenic protein Receptor tyrosine kinase-like orphan receptor 1 (ROR1) by using strictinin, a small molecule ROR1 inhibitor.
The methods performed in this study include western blots, methyl thiazolyl tetrazolium (MTT) proliferation assays, phosphatidylserine apoptosis assays, apoptosis flow cytometry (Annexin V, caspase 3/7), migration scratch assays, Boyden chamber invasion assays, and cell cycle flow cytometry.
Strictinin was most lethal against PC3 [half-maximal drug inhibitory concentration (IC50) of 277.2 µmol/L], an ARneg-AI cell type that expresses the highest levels of ROR1. Strictinin inhibited ROR1 expression, downstream phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-glycogen synthase kinase 3beta (GSK3β) pro-survival signaling, and epithelial-to-mesenchymal transition markers in PC3 cells. Additionally, strictinin decreased PC3 cell migration and invasion, while increasing S-phase cell cycle arrest. In ARneg-AI DU145 cells, strictinin inhibited ROR1 expression and modulated downstream AKT-GSK3β signaling. Furthermore, strictinin exhibited anti-migratory, anti-invasive, but minimal pro-apoptotic effects in DU145 cells likely due to DU145 having less ROR1 expression in comparison to PC3 cells. Throughout the study, strictinin minimally impacted the phenotype of normal prostatic epithelial cells RWPE-1 (IC50 of 658.5 µmol/L). Strictinin was further identified as synergistic with docetaxel [combination index (CI) = 0.311] and the combination therapy was found to reduce the IC50 of strictinin to 38.71 µmol/L in PC3 cells.
ROR1 is an emerging molecular target that can be utilized for treating prostate cancer. The data from this study establishes strictinin as a potential therapeutic agent that targets ARneg-AI prostate cancer with elevated ROR1 expression to reduce the migration, invasion, cell cycle progression, and survival of prostate cancer.
In response to DNA damage the serine/threonine-specific protein kinase checkpoint kinase 1 (CHK1) is activated allowing cells to enter S phase (S) and G2 phase (G2) cell-cycle arrest. CHK1 inhibitors are expected to prevent cells from entering such arrest, thereby enhancing DNA damage-induced cytotoxicity. In contrast, normal cells with intact ataxia–telangiectasia mutated (ATM), CHK2 and tumour suppressor protein 53 (P53) signalling are still able to enter cell-cycle arrest using the functioning G1/S checkpoint, thereby being rescued from enhanced cytotoxicity. The main objective of this work is to investigate the in vitro effects of the novel CHK1 inhibitor SRA737 on pairs of non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) cell lines, all with genetic aberrations rendering them susceptible to replication stress but of differing tumour protein 53 (TP53) gene status, focusing on DNA damage induction and the subsequent effects on cell proliferation and viability.
NSCLC cell lines H23 [TP53 mutant (MUT)] and A549 [TP53 wild-type (WT)] and CRC cell lines HT29 (TP53 MUT) and HCT116 (TP53 WT) were incubated with differing micromolar concentrations of SRA737 for 24 h and then analysed using alkaline comet and phosphorylated H2A.X variant histone (γH2AX)-foci assays to assess mostly DNA single strand break and double strand break damage, respectively. Cell-counting/trypan blue staining was also performed to assess cell proliferation/viability.
Clear concentration-dependent increases in comet formation and γH2AX-foci/cell were noted for the TP53 MUT cells with no or lower increases being noted in the corresponding TP53 WT cells. Also, greater anti-proliferative and cell killing effects were noted in the TP53 MUT cells than in the TP53 WT cells.
This study’s data suggests that P53 status/functioning is a key factor in determining the sensitivity of NSCLC and CRC cancer cells towards CHK1 inhibition, even in circumstances conducive to high replicative stress.
A generalized therapeutic strategy for various disease conditions, including cancer, is to deplete or inactivate harmful protein targets. Various forms of protein or gene silencing molecules, e.g., small molecule inhibitors, RNA interference (RNAi), and microRNAs (miRNAs) have been used against druggable targets. Over the past few years, targeted protein degradation (TPD) approaches have been developed for direct degradation of candidate proteins. Among the TPD approaches, proteolysis targeting chimeras (PROTACs) have emerged as one of the most promising approaches for the selective elimination of proteins via the ubiquitin-proteasome system. Other than PROTACs, TPD methods with potential therapeutic use include intrabody-mediated protein knockdown and tripartite motif-21 (TRIM-21) mediated TRIM-Away. In this review, protein knockdown approaches, their modes of action, and their advantages over conventional gene knockdown approaches are summarized. In cancers, disease-associated protein functions are often executed by specific post-translational modifications (PTMs). The role of TRIM-Away is highlighted in the direct knockdown of PTM forms of target proteins. Moreover, the application challenges and the prospective clinical use of TPD approaches in various diseases are also discussed.
[Names] => Mansi Joshi ... Abhijit De [Doi] => 10.37349/etat.2023.00194 [Published] => December 26, 2023 [Viewed] => 858 [Downloaded] => 38 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00194 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 132 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:1227–1248 [Recommend] => 0 [Keywords] => Protein knockdown, post-translational modification, proteolysis targeting chimeras, intrabodies, tripartite motif-21, cancer [DetailTitle] => Posttranslational Modifications in Health and Disease [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/132 [Id] => 1002194 [ris] => https://www.explorationpub.com/uploads/Article/A1002194/2408ddb4ea05b90151f95aa32e5181dc.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002194/a7478c1cd0c611b5c4e82e6f2ff1b3d5.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Joshi M, Dey P, De A. Recent advancements in targeted protein knockdown technologies—emerging paradigms for targeted therapy. Explor Target Antitumor Ther. 2023;4:1227–48. https://doi.org/10.37349/etat.2023.00194 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-12-26 06:37:11 [Bib_Time] => 2023-12-26 06:37:11 [KeysWordContens] => Recent advancements in targeted protein knockdown technologies—emerging paradigms for targeted therapy, Protein knockdown, post-translational modification, proteolysis targeting chimeras, intrabodies, tripartite motif-21, cancer, A generalized therapeutic strategy for various disease conditions, including cancer, is to deplete or inactivate harmful protein targets. Various forms of protein or gene silencing molecules, e.g., small molecule inhibitors, RNA interference (RNAi), and microRNAs (miRNAs) have been used against druggable targets. Over the past few years, targeted protein degradation (TPD) approaches have been developed for direct degradation of candidate proteins. Among the TPD approaches, proteolysis targeting chimeras (PROTACs) have emerged as one of the most promising approaches for the selective elimination of proteins via the ubiquitin-proteasome system. Other than PROTACs, TPD methods with potential therapeutic use include intrabody-mediated protein knockdown and tripartite motif-21 (TRIM-21) mediated TRIM-Away. In this review, protein knockdown approaches, their modes of action, and their advantages over conventional gene knockdown approaches are summarized. In cancers, disease-associated protein functions are often executed by specific post-translational modifications (PTMs). The role of TRIM-Away is highlighted in the direct knockdown of PTM forms of target proteins. Moreover, the application challenges and the prospective clinical use of TPD approaches in various diseases are also discussed. ,Mansi Joshi ... Abhijit De [PublishedText] => Published [IsEdit] => 0 [AccountId] => 77 [Zh] => 1 ) [196] => Array ( [ArticleId] => 1009 [Create_Time] => 2023-12-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240227065936.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002195/1002195.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002195/1002195.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002195/1002195_cover.png [JournalsId] => 4 [Title] => Telehealth in breast cancer following the coronavirus disease 2019 pandemic [Abstract] => Breast cancer (BC) is the second most diagnosed cancer in 2018 with around 2.3 million cases globally in 2020. In March 2020 and after its worldwide spread, the World Health Organization (WHO) decla [AbstractComplete] =>Breast cancer (BC) is the second most diagnosed cancer in 2018 with around 2.3 million cases globally in 2020. In March 2020 and after its worldwide spread, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak, a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, a pandemic. During this time, cancer patients were heavily impacted and their treatment plans were changed due to measures to fight the disease and solutions had to be found to maintain their follow-up and management from a distance. Some cancer groups worldwide have recommended then the use of telemedicine for oncology patients to ensure the continuity of medical care during the pandemic. This method was considered effective and clinicians worldwide continued using telehealth even after the cessation of worldwide restrictions. To this end, current up-to-date data on the use of telemedicine in BC patient after the COVID-19 outbreak are summarized in this narrative review.
[Names] => Jean Zeghondy ... Barbara Pistilli [Doi] => 10.37349/etat.2023.00195 [Published] => December 26, 2023 [Viewed] => 429 [Downloaded] => 9 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00195 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 43 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:1249–1259 [Recommend] => 0 [Keywords] => Telehealth, telemedicine, breast cancer, breast neoplasms, coronavirus disease 2019, pandemic [DetailTitle] => COVID-19 and Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/43 [Id] => 1002195 [ris] => https://www.explorationpub.com/uploads/Article/A1002195/904538a26bc9f3899868f83aea3b0968.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002195/8422c6bf141175c2f73a79b25f908c34.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Zeghondy J, Rassy E, Lapidari P, Eid R, Pistilli B. Telehealth in breast cancer following the coronavirus disease 2019 pandemic. Explor Target Antitumor Ther. 2023;4:1249–59. https://doi.org/10.37349/etat.2023.00195 [Jindex] => 0 [CName] => JeanZeghondy, [CEmail] => jean.zeghondy@gustaveroussy.fr, [Ris_Time] => 2023-12-19 02:02:02 [Bib_Time] => 2023-12-19 02:02:02 [KeysWordContens] => Telehealth in breast cancer following the coronavirus disease 2019 pandemic, Telehealth, telemedicine, breast cancer, breast neoplasms, coronavirus disease 2019, pandemic, Breast cancer (BC) is the second most diagnosed cancer in 2018 with around 2.3 million cases globally in 2020. In March 2020 and after its worldwide spread, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak, a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, a pandemic. During this time, cancer patients were heavily impacted and their treatment plans were changed due to measures to fight the disease and solutions had to be found to maintain their follow-up and management from a distance. Some cancer groups worldwide have recommended then the use of telemedicine for oncology patients to ensure the continuity of medical care during the pandemic. This method was considered effective and clinicians worldwide continued using telehealth even after the cessation of worldwide restrictions. To this end, current up-to-date data on the use of telemedicine in BC patient after the COVID-19 outbreak are summarized in this narrative review. ,Jean Zeghondy ... Barbara Pistilli [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [197] => Array ( [ArticleId] => 1017 [Create_Time] => 2023-12-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202312/20231227063909.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002196/1002196.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002196/1002196.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002196/1002196_cover.png [JournalsId] => 4 [Title] => Post-translational modulation of cell signalling through protein succinylation [Abstract] => Cells need to adapt their activities to extra- and intracellular signalling cues. To translate a received extracellular signal, cells have specific receptors that transmit the signal to downstream p [AbstractComplete] =>Cells need to adapt their activities to extra- and intracellular signalling cues. To translate a received extracellular signal, cells have specific receptors that transmit the signal to downstream proteins so that it can reach the nucleus to initiate or repress gene transcription. Post-translational modifications (PTMs) of proteins are reversible or irreversible chemical modifications that help to further modulate protein activity. The most commonly observed PTMs are the phosphorylation of serine, threonine, and tyrosine residues, followed by acetylation, glycosylation, and amidation. In addition to PTMs that involve the modification of a certain amino acid (phosphorylation, hydrophobic groups for membrane localisation, or chemical groups like acylation), or the conjugation of peptides (SUMOylation, NEDDylation), structural changes such as the formation of disulphide bridge, protein cleavage or splicing can also be classified as PTMs. Recently, it was discovered that metabolites from the tricarboxylic acid (TCA) cycle are not only intermediates that support cellular metabolism but can also modify lysine residues. This has been shown for acetate, succinate, and lactate, among others. Due to the importance of mitochondria for the overall fitness of organisms, the regulatory function of such PTMs is critical for protection from aging, neurodegeneration, or cardiovascular disease. Cancer cells and activated immune cells display a phenotype of accelerated metabolic activity known as the Warburg effect. This metabolic state is characterised by enhanced glycolysis, the use of the pentose phosphate pathway as well as a disruption of the TCA cycle, ultimately causing the accumulation of metabolites like citrate, succinate, and malate. Succinate can then serve as a signalling molecule by directly interacting with proteins, by binding to its G protein-coupled receptor 91 (GPR91) and by post-translationally modifying proteins through succinylation of lysine residues, respectively. This review is focus on the process of protein succinylation and its importance in health and disease.
[Names] => Katharina F. Kubatzky ... Dayoung Yu [Doi] => 10.37349/etat.2023.00196 [Published] => December 27, 2023 [Viewed] => 867 [Downloaded] => 33 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00196 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 132 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:1260–1285 [Recommend] => 0 [Keywords] => Succinate, metabolites, mitochondria, post-translational modifications, lysine succinylation, cancer, immune system [DetailTitle] => Posttranslational Modifications in Health and Disease [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/132 [Id] => 1002196 [ris] => https://www.explorationpub.com/uploads/Article/A1002196/59fcc62bef907c1e4bacf70f2ba6fad8.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002196/c617ef76851448e5ee0791809fabd466.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Kubatzky KF, Gao Y, Yu D. Post-translational modulation of cell signalling through protein succinylation. Explor Target Antitumor Ther. 2023;4:1260–85. https://doi.org/10.37349/etat.2023.00196 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-12-27 06:39:09 [Bib_Time] => 2023-12-27 06:39:09 [KeysWordContens] => Post-translational modulation of cell signalling through protein succinylation, Succinate, metabolites, mitochondria, post-translational modifications, lysine succinylation, cancer, immune system, Cells need to adapt their activities to extra- and intracellular signalling cues. To translate a received extracellular signal, cells have specific receptors that transmit the signal to downstream proteins so that it can reach the nucleus to initiate or repress gene transcription. Post-translational modifications (PTMs) of proteins are reversible or irreversible chemical modifications that help to further modulate protein activity. The most commonly observed PTMs are the phosphorylation of serine, threonine, and tyrosine residues, followed by acetylation, glycosylation, and amidation. In addition to PTMs that involve the modification of a certain amino acid (phosphorylation, hydrophobic groups for membrane localisation, or chemical groups like acylation), or the conjugation of peptides (SUMOylation, NEDDylation), structural changes such as the formation of disulphide bridge, protein cleavage or splicing can also be classified as PTMs. Recently, it was discovered that metabolites from the tricarboxylic acid (TCA) cycle are not only intermediates that support cellular metabolism but can also modify lysine residues. This has been shown for acetate, succinate, and lactate, among others. Due to the importance of mitochondria for the overall fitness of organisms, the regulatory function of such PTMs is critical for protection from aging, neurodegeneration, or cardiovascular disease. Cancer cells and activated immune cells display a phenotype of accelerated metabolic activity known as the Warburg effect. This metabolic state is characterised by enhanced glycolysis, the use of the pentose phosphate pathway as well as a disruption of the TCA cycle, ultimately causing the accumulation of metabolites like citrate, succinate, and malate. Succinate can then serve as a signalling molecule by directly interacting with proteins, by binding to its G protein-coupled receptor 91 (GPR91) and by post-translationally modifying proteins through succinylation of lysine residues, respectively. This review is focus on the process of protein succinylation and its importance in health and disease. ,Katharina F. Kubatzky ... Dayoung Yu [PublishedText] => Published [IsEdit] => 0 [AccountId] => 77 [Zh] => 1 ) [198] => Array ( [ArticleId] => 1020 [Create_Time] => 2023-12-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202312/20231228015029.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002197/1002197.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002197/1002197.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002197/1002197_Cover.png [JournalsId] => 4 [Title] => Current implications and challenges of artificial intelligence technologies in therapeutic intervention of colorectal cancer [Abstract] => Irrespective of men and women, colorectal cancer (CRC), is the third most common cancer in the population with more than 1.85 million cases annually. Fewer than 20% of patients only survive beyond f [AbstractComplete] =>Irrespective of men and women, colorectal cancer (CRC), is the third most common cancer in the population with more than 1.85 million cases annually. Fewer than 20% of patients only survive beyond five years from diagnosis. CRC is a highly preventable disease if diagnosed at the early stage of malignancy. Several screening methods like endoscopy (like colonoscopy; gold standard), imaging examination [computed tomographic colonography (CTC)], guaiac-based fecal occult blood (gFOBT), immunochemical test from faeces, and stool DNA test are available with different levels of sensitivity and specificity. The available screening methods are associated with certain drawbacks like invasiveness, cost, or sensitivity. In recent years, computer-aided systems-based screening, diagnosis, and treatment have been very promising in the early-stage detection and diagnosis of CRC cases. Artificial intelligence (AI) is an enormously in-demand, cost-effective technology, that uses various tools machine learning (ML), and deep learning (DL) to screen, diagnose, and stage, and has great potential to treat CRC. Moreover, different ML algorithms and neural networks [artificial neural network (ANN), k-nearest neighbors (KNN), and support vector machines (SVMs)] have been deployed to predict precise and personalized treatment options. This review examines and summarizes different ML and DL models used for therapeutic intervention in CRC cancer along with the gap and challenges for AI.
[Names] => Kriti Das ... Chakresh Kumar Jain [Doi] => 10.37349/etat.2023.00197 [Published] => December 27, 2023 [Viewed] => 621 [Downloaded] => 21 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00197 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 88 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:1286–1300 [Recommend] => 0 [Keywords] => Artificial intelligence, machine learning, deep learning, colorectal cancer, drug discovery [DetailTitle] => Artificial Intelligence for Precision Oncology [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/88 [Id] => 1002197 [ris] => https://www.explorationpub.com/uploads/Article/A1002197/38ec4d098d885fbf6f7a61785aa50b0b.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002197/f15010c566d9833598878f3f778e6246.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Das K, Paltani M, Tripathi PK, Kumar R, Verma S, Kumar S, et al. Current implications and challenges of artificial intelligence technologies in therapeutic intervention of colorectal cancer. Explor Target Antitumor Ther. 2023;4:1286–300. https://doi.org/10.37349/etat.2023.00197 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-12-21 02:27:03 [Bib_Time] => 2023-12-21 02:27:03 [KeysWordContens] => Current implications and challenges of artificial intelligence technologies in therapeutic intervention of colorectal cancer, Artificial intelligence, machine learning, deep learning, colorectal cancer, drug discovery, Irrespective of men and women, colorectal cancer (CRC), is the third most common cancer in the population with more than 1.85 million cases annually. Fewer than 20% of patients only survive beyond five years from diagnosis. CRC is a highly preventable disease if diagnosed at the early stage of malignancy. Several screening methods like endoscopy (like colonoscopy; gold standard), imaging examination [computed tomographic colonography (CTC)], guaiac-based fecal occult blood (gFOBT), immunochemical test from faeces, and stool DNA test are available with different levels of sensitivity and specificity. The available screening methods are associated with certain drawbacks like invasiveness, cost, or sensitivity. In recent years, computer-aided systems-based screening, diagnosis, and treatment have been very promising in the early-stage detection and diagnosis of CRC cases. Artificial intelligence (AI) is an enormously in-demand, cost-effective technology, that uses various tools machine learning (ML), and deep learning (DL) to screen, diagnose, and stage, and has great potential to treat CRC. Moreover, different ML algorithms and neural networks [artificial neural network (ANN), k-nearest neighbors (KNN), and support vector machines (SVMs)] have been deployed to predict precise and personalized treatment options. This review examines and summarizes different ML and DL models used for therapeutic intervention in CRC cancer along with the gap and challenges for AI. ,Kriti Das ... Chakresh Kumar Jain [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [199] => Array ( [ArticleId] => 1023 [Create_Time] => 2023-12-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202312/20231228001631.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002198/1002198.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002198/1002198.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002198/1002198-cover.png [JournalsId] => 4 [Title] => Facing the conundrum: which first-line therapy should be used for patients with metastatic triple-negative breast cancer carrying germline BRCA mutation? [Abstract] => Pembrolizumab combined with chemotherapy has been established as the preferred first-line therapy for treating metastatic triple-negative breast cancer (mTNBC) with programmed cell death ligand-1 (P [AbstractComplete] =>Pembrolizumab combined with chemotherapy has been established as the preferred first-line therapy for treating metastatic triple-negative breast cancer (mTNBC) with programmed cell death ligand-1 (PD-L1)-positive disease since its approval for that indication. However, the optimal sequencing of therapy remains an unanswered question for a subset of mTNBC patients who harbor germline breast cancer gene 1/2 (BRCA1/2; gBRCA1/2) mutation. This article aims to offer insights into the optimal therapy sequencing for mTNBC patients with gBRCA1/2 mutations and its impact on clinical decision-making. The perspective offered is based on the best currently available data and propose a practical algorithm to guide the management of this subgroup in the frontline setting.
[Names] => Sabah Alaklabi ... Shipra Gandhi [Doi] => 10.37349/etat.2023.00198 [Published] => December 27, 2023 [Viewed] => 514 [Downloaded] => 12 [Subject] => Perspective [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00198 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 137 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2023;4:1301–1309 [Recommend] => 0 [Keywords] => Metastatic triple-negative breast cancer, programmed cell death ligand-1, Poly (ADP-ribose) polymerase inhibitor, sequencing of therapy, targeted therapy [DetailTitle] => Innovative Strategies to Target Triple-negative Breast Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/137 [Id] => 1002198 [ris] => https://www.explorationpub.com/uploads/Article/A1002198/5344bf95e1e109c83020d520e8871ecb.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002198/bab2907bf3f79b06fcc8aca771303ba6.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Alaklabi S, Roy AM, Chaudhary LN, Gandhi S. Facing the conundrum: which first-line therapy should be used for patients with metastatic triple-negative breast cancer carrying germline BRCA mutation? Explor Target Antitumor Ther. 2023;4:1301–9. https://doi.org/10.37349/etat.2023.00198 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-12-21 03:31:43 [Bib_Time] => 2023-12-21 03:31:43 [KeysWordContens] => Facing the conundrum: which first-line therapy should be used for patients with metastatic triple-negative breast cancer carrying germline BRCA mutation?, Metastatic triple-negative breast cancer, programmed cell death ligand-1, Poly (ADP-ribose) polymerase inhibitor, sequencing of therapy, targeted therapy, Pembrolizumab combined with chemotherapy has been established as the preferred first-line therapy for treating metastatic triple-negative breast cancer (mTNBC) with programmed cell death ligand-1 (PD-L1)-positive disease since its approval for that indication. However, the optimal sequencing of therapy remains an unanswered question for a subset of mTNBC patients who harbor germline breast cancer gene 1/2 (BRCA1/2; gBRCA1/2) mutation. This article aims to offer insights into the optimal therapy sequencing for mTNBC patients with gBRCA1/2 mutations and its impact on clinical decision-making. The perspective offered is based on the best currently available data and propose a practical algorithm to guide the management of this subgroup in the frontline setting. ,Sabah Alaklabi ... Shipra Gandhi [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [200] => Array ( [ArticleId] => 1025 [Create_Time] => 2023-12-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202312/20231229060024.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002199/1002199.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002199/1002199.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002199/1002199_cover.png [JournalsId] => 4 [Title] => Therapeutic significance of tumor microenvironment in cholangiocarcinoma: focus on tumor-infiltrating T lymphocytes [Abstract] => Cholangiocarcinoma (CCA) is a highly aggressive type of adenocarcinoma distinguished by its invasiveness. Depending on specific anatomical positioning within the biliary tree, CCA can be categorized [AbstractComplete] =>Cholangiocarcinoma (CCA) is a highly aggressive type of adenocarcinoma distinguished by its invasiveness. Depending on specific anatomical positioning within the biliary tree, CCA can be categorized into intrahepatic CCA (ICCA), perihilar CCA (pCCA) and distal CCA (dCCA). In recent years, there has been a significant increase in the global prevalence of CCA. Unfortunately, many CCA patients are diagnosed at an advanced stage, which makes surgical resection impossible. Although systemic chemotherapy is frequently used as the primary treatment for advanced or recurrent CCA, its effectiveness is relatively low. Therefore, immunotherapy has emerged as a promising avenue for advancing cancer treatment research. CCA exhibits a complex immune environment within the stromal tumor microenvironment (TME), comprising a multifaceted immune landscape and a tumor-reactive stroma. A deeper understanding of this complex TME is indispensable for identifying potential therapeutic targets. Thus, targeting tumor immune microenvironment holds promise as an effective therapeutic strategy.
[Names] => Chaoqun Li ... Jieer Ying [Doi] => 10.37349/etat.2023.00199 [Published] => December 28, 2023 [Viewed] => 643 [Downloaded] => 9 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2023.00199 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 175 [TitleAbbr] => Explor Target Antitumor Ther [Pages] => 2023;4:1310–1327 [Recommend] => 0 [Keywords] => Tumor microenvironment, cholangiocarcinoma, tumor-infiltrating T lymphocytes, molecular pathogenesis, immunotherapy [DetailTitle] => Novel Strategies and Targets for Immunotherapy of Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/175 [Id] => 1002199 [ris] => https://www.explorationpub.com/uploads/Article/A1002199/ab8e30f1b2e3297d2d3a9770b28efe83.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002199/738c764109da8588e2c85f641b86373f.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Li C, Bie L, Chen M, Ying J. Therapeutic significance of tumor microenvironment in cholangiocarcinoma: focus on tumor-infiltrating T lymphocytes. Explor Target Antitumor Ther. 2023;4:1310–27. https://doi.org/10.37349/etat.2023.00199 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-12-21 08:01:24 [Bib_Time] => 2023-12-21 08:01:24 [KeysWordContens] => Therapeutic significance of tumor microenvironment in cholangiocarcinoma: focus on tumor-infiltrating T lymphocytes, Tumor microenvironment, cholangiocarcinoma, tumor-infiltrating T lymphocytes, molecular pathogenesis, immunotherapy, Cholangiocarcinoma (CCA) is a highly aggressive type of adenocarcinoma distinguished by its invasiveness. Depending on specific anatomical positioning within the biliary tree, CCA can be categorized into intrahepatic CCA (ICCA), perihilar CCA (pCCA) and distal CCA (dCCA). In recent years, there has been a significant increase in the global prevalence of CCA. Unfortunately, many CCA patients are diagnosed at an advanced stage, which makes surgical resection impossible. Although systemic chemotherapy is frequently used as the primary treatment for advanced or recurrent CCA, its effectiveness is relatively low. Therefore, immunotherapy has emerged as a promising avenue for advancing cancer treatment research. CCA exhibits a complex immune environment within the stromal tumor microenvironment (TME), comprising a multifaceted immune landscape and a tumor-reactive stroma. A deeper understanding of this complex TME is indispensable for identifying potential therapeutic targets. Thus, targeting tumor immune microenvironment holds promise as an effective therapeutic strategy. ,Chaoqun Li ... Jieer Ying [PublishedText] => Published [IsEdit] => 0 [AccountId] => 87 [Zh] => 1 ) [201] => Array ( [ArticleId] => 1064 [Create_Time] => 2023-12-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202312/20231229093302.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002200/1002200.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002200/1002200.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002200/1002200-cover.png [JournalsId] => 4 [Title] => Cola rostrata K. Schum. constituents induce cytotoxicity through reactive oxygen species generation and mitochondrial membrane depolarisation [Abstract] => Aim: While the traditional use of Cola rostrata in treating illnesses and diseases has not been reported, the presence of cytotoxic principles has been reported in phylogenetically and biogeograp [AbstractComplete] =>While the traditional use of Cola rostrata in treating illnesses and diseases has not been reported, the presence of cytotoxic principles has been reported in phylogenetically and biogeographically related species within the Cola genus. This study, therefore, evaluated the cytotoxic potential of extracts of the plant, and the associated cellular and molecular mechanisms.
Activity-based fractionation of the extracts was carried out and cytotoxicity was assessed in the human cervical cancer cell line, HeLa, and the transformed human lung cell line, MRC5-SV2, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay complemented with brightfield imaging. The 2ʼ,7ʼ-dichlorofluorescein diacetate (DCFDA) assay was used to assess induction of cellular reactive oxygen species (ROS), while flow cytometry of 5,5ʼ,6,6ʼ-tetrachloro-1,1ʼ,3,3ʼ-tetraethyl-imidacarbocyanine iodide (JC-1)-stained cells assessed the loss of mitochondrial membrane potential (∆ΨM). Gas chromatography-mass spectrometry (GC-MS) analysis was carried out on an active fraction.
Extracts of the fruit epicarp and leaf were cytotoxic against the cell lines. Half-maximal inhibitory concentration (IC50) values for the 48 h cytotoxicity of the ethanol extract of the epicarp against HeLa and MRC5-SV2 cells were 48.0 μg/mL ± 12.1 μg/mL and 40.4 μg/mL ± 7.2 μg/mL, respectively, while fractions from second-level partitioning of the hexane fraction of the leaf extract elicited cytotoxicity with IC50 values ranging from 12.8 μg/mL ± 1.0 μg/mL to 39.6 μg/mL ± 7.2 μg/mL in both cell lines, following 48 h treatment. GC-MS revealed the presence of seventeen compounds in a hexane fraction of the leaf extract, including even- and odd-chain fatty acids, the most abundant of which were n-hexadecanoic acid, decanoic acid 10-(2-hexylcyclopropyl); and octadecanoic acid. The mechanisms of cytotoxicity of most active fractions involved generation of ROS and mitochondrial membrane depolarisation.
The findings show that C. rostrata is rich in cytotoxic phytochemicals which could be isolated for developing new anti-cancer agents.
Breast cancer (BC) is the most common cancer in women worldwide, where adiposity has been linked to BC morbidity. In general, obese premenopausal women diagnosed with triple-negative BC (TNBC) tend to have larger tumours with more metastases, particularly to the bone marrow, and worse prognosis. Previous work using a 3-dimensional (3D) co-culture system consisting of TNBC cells, adipocytes and the laminin-rich extracellular matrix (ECM) trademarked as Matrigel, demonstrated that adipocytes and adipocyte-derived conditioned media (CM) caused a partial mesenchymal-to-epithelial transition (MET). Given that MET has been associated with secondary tumour formation, this study sought to identify molecular mediators responsible for this phenotypic change.
Adipocytes were cultured with and without Matrigel, where semi-quantitative proteomics was used to identify proteins whose presence in the CM was induced or enhanced by Matrigel, which were referred to as adipocyte-secreted ECM-induced proteins (AEPs). The AEPs identified were assessed for association with prognosis in published proteomic datasets and prior literature. Of these, 4 were evaluated by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), followed by a functional and MET marker analysis of 1 AEP on MDA-MB-231 cells grown on Matrigel or as monolayers.
The 4 AEPs showed a positive correlation between protein expression and poor prognosis. RT-qPCR analysis reported no significant change in AEPs mRNA expression. However, lysyl oxidase (LOX) was increased in CM of ECM-exposed adipocytes. Recombinant LOX (rLOX) caused the mesenchymal MDA-MB-231 TNBC cells to form less branched 3D structures and reduced the expression of vimentin.
The data suggest that adipocyte-secreted LOX changes the mesenchymal phenotype of BC cells in a manner that could promote secondary tumour formation, particularly at sites high in adipocytes such as the bone marrow. Future efforts should focus on determining whether targeting LOX could reduce BC metastasis in obese individuals.
Pancreatic cancer remains a serious and deadly disease, impacting people globally. There remain prominent gaps in the current understanding of the disease, specifically regarding the role of the signal transducer and activator of transcription (STAT) family of proteins in pancreatic tumors. STAT proteins, particularly STAT3, play important roles in pancreatic cancer, especially pancreatic ductal adenocarcinoma (PDAC), which is the most prevalent histotype. The role of STAT3 across a continuum of molecular processes, such as PDAC tumorigenesis and progression, immune escape, drug resistance and stemness, and modulation of the tumor microenvironment (TME), are only a tip of the iceberg. In some ways, the role of STAT3 in PDAC may hold greater importance than that of oncogenic Kirsten rat sarcoma virus (KRAS). This makes STAT3 a highly attractive target for developing targeted therapies for the treatment of pancreatic cancer. In this review, the current knowledge of STAT3 in pancreatic cancer has been summarized, particularly relating to STAT3 activation in cancer cells, cells of the TME, and the state of targeting STAT3 in pre-clinical and clinical trials of PDAC.
[Names] => Zachary Hamel ... Shrikant Anant [Doi] => 10.37349/etat.2024.00202 [Published] => January 17, 2024 [Viewed] => 575 [Downloaded] => 23 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/etat.2024.00202 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 113 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:20–33 [Recommend] => 0 [Keywords] => Signal transducer and activator of transcription, tumor microenvironment, pancreatic cancer [DetailTitle] => Therapeutic Targeting of the Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/113 [Id] => 1002202 [ris] => https://www.explorationpub.com/uploads/Article/A1002202/d8a65979070dbdd708791ec15939044e.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002202/51792ac8194094a686215fdb805f2ffd.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Hamel Z, Sanchez S, Standing D, Anant S. Role of STAT3 in pancreatic cancer. Explor Target Antitumor Ther. 2024;5:20–33. https://doi.org/10.37349/etat.2024.00202 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-01-16 00:52:30 [Bib_Time] => 2024-01-16 00:52:30 [KeysWordContens] => Role of STAT3 in pancreatic cancer, Signal transducer and activator of transcription, tumor microenvironment, pancreatic cancer, Pancreatic cancer remains a serious and deadly disease, impacting people globally. There remain prominent gaps in the current understanding of the disease, specifically regarding the role of the signal transducer and activator of transcription (STAT) family of proteins in pancreatic tumors. STAT proteins, particularly STAT3, play important roles in pancreatic cancer, especially pancreatic ductal adenocarcinoma (PDAC), which is the most prevalent histotype. The role of STAT3 across a continuum of molecular processes, such as PDAC tumorigenesis and progression, immune escape, drug resistance and stemness, and modulation of the tumor microenvironment (TME), are only a tip of the iceberg. In some ways, the role of STAT3 in PDAC may hold greater importance than that of oncogenic Kirsten rat sarcoma virus (KRAS). This makes STAT3 a highly attractive target for developing targeted therapies for the treatment of pancreatic cancer. In this review, the current knowledge of STAT3 in pancreatic cancer has been summarized, particularly relating to STAT3 activation in cancer cells, cells of the TME, and the state of targeting STAT3 in pre-clinical and clinical trials of PDAC. ,Zachary Hamel ... Shrikant Anant [PublishedText] => Published [IsEdit] => 0 [AccountId] => 88 [Zh] => 1 ) [204] => Array ( [ArticleId] => 1085 [Create_Time] => 2024-01-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202401/20240129031342.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002203/1002203.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002203/1002203.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002203/1002203_cover.png [JournalsId] => 4 [Title] => DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine [Abstract] => Colorectal cancer (CRC) is a multifaceted disease influenced by the interplay of genetic and environmental factors. The clinical heterogeneity of CRC cannot be attributed exclusively to genetic dive [AbstractComplete] =>Colorectal cancer (CRC) is a multifaceted disease influenced by the interplay of genetic and environmental factors. The clinical heterogeneity of CRC cannot be attributed exclusively to genetic diversity and environmental exposures, and epigenetic markers, especially DNA methylation, play a critical role as key molecular markers of cancer. This review compiles a comprehensive body of evidence underscoring the significant involvement of DNA methylation modifications in the pathogenesis of CRC. Moreover, this review explores the potential utility of DNA methylation in cancer diagnosis, prognostics, assessment of disease activity, and prediction of drug responses. Recognizing the impact of DNA methylation will enhance the ability to identify distinct CRC subtypes, paving the way for personalized treatment strategies and advancing precision medicine in the management of CRC.
[Names] => Jingxin Ye ... Weifeng Ding [Doi] => 10.37349/etat.2024.00203 [Published] => January 28, 2024 [Viewed] => 642 [Downloaded] => 29 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00203 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 258 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:34–53 [Recommend] => 0 [Keywords] => Epigenetic modification, DNA methylation, colorectal cancer, diagnosis, metabolism reprogramming [DetailTitle] => Cancer Epigenetics: Implications for Novel Therapeutic Strategies [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/258 [Id] => 1002203 [ris] => https://www.explorationpub.com/uploads/Article/A1002203/01ac4fb09eed92710445402f38370fe2.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002203/8b2b55f4fa7c967d79fbd7dae941aaa1.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Ye J, Zhang J, Ding W. DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine. Explor Target Antitumor Ther. 2024;5:34–53. https://doi.org/10.37349/etat.2024.00203 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-01-22 08:09:45 [Bib_Time] => 2024-01-22 08:09:45 [KeysWordContens] => DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine, Epigenetic modification, DNA methylation, colorectal cancer, diagnosis, metabolism reprogramming, Colorectal cancer (CRC) is a multifaceted disease influenced by the interplay of genetic and environmental factors. The clinical heterogeneity of CRC cannot be attributed exclusively to genetic diversity and environmental exposures, and epigenetic markers, especially DNA methylation, play a critical role as key molecular markers of cancer. This review compiles a comprehensive body of evidence underscoring the significant involvement of DNA methylation modifications in the pathogenesis of CRC. Moreover, this review explores the potential utility of DNA methylation in cancer diagnosis, prognostics, assessment of disease activity, and prediction of drug responses. Recognizing the impact of DNA methylation will enhance the ability to identify distinct CRC subtypes, paving the way for personalized treatment strategies and advancing precision medicine in the management of CRC. ,Jingxin Ye ... Weifeng Ding [PublishedText] => Published [IsEdit] => 0 [AccountId] => 87 [Zh] => 1 ) [205] => Array ( [ArticleId] => 1090 [Create_Time] => 2024-02-19 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240208031015.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002204/1002204.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002204/1002204.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002204/1002204_cover.png [JournalsId] => 4 [Title] => Efficacy of metformin and electrical pulses in breast cancer MDA-MB-231 cells [Abstract] => Aim: Triple-negative breast cancer (TNBC) is a very aggressive subset of breast cancer, with limited treatment options, due to the lack of three commonly targeted receptors, which merits the need [AbstractComplete] =>Triple-negative breast cancer (TNBC) is a very aggressive subset of breast cancer, with limited treatment options, due to the lack of three commonly targeted receptors, which merits the need for novel treatments for TNBC. Towards this need, the use of metformin (Met), the most widely used type-2 diabetes drug worldwide, was explored as a repurposed anticancer agent. Cancer being a metabolic disease, the modulation of two crucial metabolites, glucose, and reactive oxygen species (ROS), is studied in MDA-MB-231 TNBC cells, using Met in the presence of electrical pulses (EP) to enhance the drug efficacy.
MDA-MB-231, human TNBC cells were treated with Met in the presence of EP, with various concentrations Met of 1 mmol/L, 2.5 mmol/L, 5 mmol/L, and 10 mmol/L. EP of 500 V/cm, 800 V/cm, and 1,000 V/cm (with a pulse width of 100 µs at 1 s intervals) were applied to TNBC and the impact of these two treatments was studied. Various assays, including cell viability, microscopic inspection, glucose, ROS, and wound healing assay, were performed to characterize the response of the cells to the combination treatment.
Combining 1,000 V/cm with 5 mmol/L Met yielded cell viability as low as 42.6% at 24 h. The glucose level was reduced by 5.60-fold and the ROS levels were increased by 9.56-fold compared to the control, leading to apoptotic cell death.
The results indicate the enhanced anticancer effect of Met in the presence of electric pulses. The cell growth is inhibited by suppressing glucose levels and elevated ROS. This shows a synergistic interplay between electroporation, Met, glucose, and ROS metabolic alterations. The results show promises for combinational therapy in TNBC patients.
To investigate magnetic resonance imaging (MRI)-based peritumoral texture features as prognostic indicators of survival in patients with colorectal liver metastasis (CRLM).
From 2007–2015, forty-eight patients who underwent MRI within 3 months prior to initiating treatment for CRLM were identified. Clinicobiological prognostic variables were obtained from electronic medical records. Ninety-four metastatic hepatic lesions were identified on T1-weighted post-contrast images and volumetrically segmented. A total of 112 radiomic features (shape, first-order, texture) were derived from a 10 mm region surrounding each segmented tumor. A random forest model was applied, and performance was tested by receiver operating characteristic (ROC). Kaplan-Meier analysis was utilized to generate the survival curves.
Forty-eight patients (male:female = 23:25, age 55.3 years ± 18 years) were included in the study. The median lesion size was 25.73 mm (range 8.5–103.8 mm). Microsatellite instability was low in 40.4% (38/94) of tumors, with Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation detected in 68 out of 94 (72%) tumors. The mean survival was 35 months ± 21 months, and local disease progression was observed in 35.5% of patients. Univariate regression analysis identified 42 texture features [8 first order, 5 gray level dependence matrix (GLDM), 5 gray level run time length matrix (GLRLM), 5 gray level size zone matrix (GLSZM), 2 neighboring gray tone difference matrix (NGTDM), and 17 gray level co-occurrence matrix (GLCM)] independently associated with metastatic disease progression (P < 0.03). The random forest model achieved an area under the curve (AUC) of 0.88.
MRI-based peritumoral heterogeneity features may serve as predictive biomarkers for metastatic disease progression and patient survival in CRLM.
Lung cancer remains the most common cause of cancer death across the world. Non-small-cell lung cancer (NSCLC) represents the most frequent type of lung cancer and is frequently diagnosed at an advanced stage. Stage III NSCLC, which encompasses 30% of cases, refers to a state between localized and metastatic disease, and is associated with poor prognosis. As highlighted in this review, stage III represents a heterogenous group, whose complex management includes multimodal treatment, discussed below, and requires discussion in multidisciplinary teams. The goal of this approach is a maximalist attitude in these patients with locally advanced and non-metastatic disease. However, many issues remain under debate including the optimal sequences of treatment between different treatment modalities, patient selection particularly for surgery, the duration of perioperative treatments and the identification of biomarkers to determine which patients might benefit of specific treatment like immunotherapy and targeted therapies. This review describes the current landscape of management of stage III NSCLC, discussing the critical issue of resectability, and highlighting the recent advancements in the field, particularly the incorporation of immune-checkpoint inhibitors (ICIs) and targeted therapies in this setting.
[Names] => Floryane Kim ... Alex Friedlaender [Doi] => 10.37349/etat.2024.00206 [Published] => February 19, 2024 [Viewed] => 500 [Downloaded] => 28 [Subject] => Mini Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00206 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 126 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:85–95 [Recommend] => 0 [Keywords] => Non-small-cell lung cancer, stage III, perioperative immunotherapy, targeted therapy, chemo-radiotherapy, multidisciplinary management [DetailTitle] => Integrated Approaches for Non-Small-Cell Lung Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/126 [Id] => 1002206 [ris] => https://www.explorationpub.com/uploads/Article/A1002206/a0e29059bffc15753e191e38afc64161.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002206/da496369545c14c318ee6c409d614451.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Kim F, Borgeaud M, Addeo A, Friedlaender A. Management of stage III non-small-cell lung cancer: rays of hope. Explor Target Antitumor Ther. 2024;5:85–95. https://doi.org/10.37349/etat.2024.00206 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-06 01:59:46 [Bib_Time] => 2024-01-31 08:45:00 [KeysWordContens] => Management of stage III non-small-cell lung cancer: rays of hope, Non-small-cell lung cancer, stage III, perioperative immunotherapy, targeted therapy, chemo-radiotherapy, multidisciplinary management, Lung cancer remains the most common cause of cancer death across the world. Non-small-cell lung cancer (NSCLC) represents the most frequent type of lung cancer and is frequently diagnosed at an advanced stage. Stage III NSCLC, which encompasses 30% of cases, refers to a state between localized and metastatic disease, and is associated with poor prognosis. As highlighted in this review, stage III represents a heterogenous group, whose complex management includes multimodal treatment, discussed below, and requires discussion in multidisciplinary teams. The goal of this approach is a maximalist attitude in these patients with locally advanced and non-metastatic disease. However, many issues remain under debate including the optimal sequences of treatment between different treatment modalities, patient selection particularly for surgery, the duration of perioperative treatments and the identification of biomarkers to determine which patients might benefit of specific treatment like immunotherapy and targeted therapies. This review describes the current landscape of management of stage III NSCLC, discussing the critical issue of resectability, and highlighting the recent advancements in the field, particularly the incorporation of immune-checkpoint inhibitors (ICIs) and targeted therapies in this setting. ,Floryane Kim ... Alex Friedlaender [PublishedText] => Published [IsEdit] => 0 [AccountId] => 87 [Zh] => 1 ) [208] => Array ( [ArticleId] => 1111 [Create_Time] => 2024-02-19 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240222053931.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002207/1002207.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002207/1002207.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002207/1002207_cover.png [JournalsId] => 4 [Title] => CD99 tumor associated antigen is a potential target for antibody therapy of T-cell acute lymphoblastic leukemia [Abstract] => Monoclonal antibodies (mAbs) are an effective drug for targeted immunotherapy in several cancer types. However, so far, no antibody has been successfully developed for certain types of cancer, inclu [AbstractComplete] =>Monoclonal antibodies (mAbs) are an effective drug for targeted immunotherapy in several cancer types. However, so far, no antibody has been successfully developed for certain types of cancer, including T-cell acute lymphoblastic leukemia (T-ALL). T-ALL is an aggressive hematologic malignancy. T-ALL patients who are treated with chemotherapeutic drugs frequently relapse and become drug resistant. Therefore, antibody-based therapy is promising for T-ALL treatment. To successfully develop an antibody-based therapy for T-ALL, antibodies that induce death in malignant T cells but not in nonmalignant T cells are required to avoid the induction of secondary T-cell immunodeficiency. In this review, CD99 tumor associated antigen, which is highly expressed on malignant T cells and lowly expressed on nonmalignant T cells, is proposed to be a potential target for antibody therapy of T-ALL. Since certain clones of anti-CD99 mAbs induce apoptosis only in malignant T cells, these anti-CD99 mAbs might be a promising antibody drug for the treatment of T-ALL with high efficiency and low adverse effects. Moreover, over the past 25 years, many clones of anti-CD99 mAbs have been studied for their direct effects on T-ALL. These outcomes are gathered here.
[Names] => Kamonporn Kotemul ... Nuchjira Takheaw [Doi] => 10.37349/etat.2024.00207 [Published] => February 19, 2024 [Viewed] => 500 [Downloaded] => 15 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00207 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 175 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:96–107 [Recommend] => 0 [Keywords] => CD99 molecule, CD99 antibody, cancer immunotherapy, T-cell acute lymphoblastic leukemia, antibody drug, T-cell malignancy [DetailTitle] => Novel Strategies and Targets for Immunotherapy of Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/175 [Id] => 1002207 [ris] => https://www.explorationpub.com/uploads/Article/A1002207/36d0ce808a8475d1bacd599bbf704f88.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002207/912c86d7ff9195bb635a1e918e116f8e.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Kotemul K, Kasinrerk W, Takheaw N. CD99 tumor associated antigen is a potential target for antibody therapy of T-cell acute lymphoblastic leukemia. Explor Target Antitumor Ther. 2024;5:96–107. https://doi.org/10.37349/etat.2024.00207 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-06 01:31:35 [Bib_Time] => 2024-02-06 01:31:35 [KeysWordContens] => CD99 tumor associated antigen is a potential target for antibody therapy of T-cell acute lymphoblastic leukemia, CD99 molecule, CD99 antibody, cancer immunotherapy, T-cell acute lymphoblastic leukemia, antibody drug, T-cell malignancy, Monoclonal antibodies (mAbs) are an effective drug for targeted immunotherapy in several cancer types. However, so far, no antibody has been successfully developed for certain types of cancer, including T-cell acute lymphoblastic leukemia (T-ALL). T-ALL is an aggressive hematologic malignancy. T-ALL patients who are treated with chemotherapeutic drugs frequently relapse and become drug resistant. Therefore, antibody-based therapy is promising for T-ALL treatment. To successfully develop an antibody-based therapy for T-ALL, antibodies that induce death in malignant T cells but not in nonmalignant T cells are required to avoid the induction of secondary T-cell immunodeficiency. In this review, CD99 tumor associated antigen, which is highly expressed on malignant T cells and lowly expressed on nonmalignant T cells, is proposed to be a potential target for antibody therapy of T-ALL. Since certain clones of anti-CD99 mAbs induce apoptosis only in malignant T cells, these anti-CD99 mAbs might be a promising antibody drug for the treatment of T-ALL with high efficiency and low adverse effects. Moreover, over the past 25 years, many clones of anti-CD99 mAbs have been studied for their direct effects on T-ALL. These outcomes are gathered here. ,Kamonporn Kotemul ... Nuchjira Takheaw [PublishedText] => Published [IsEdit] => 0 [AccountId] => 87 [Zh] => 1 ) [209] => Array ( [ArticleId] => 1112 [Create_Time] => 2024-02-19 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240227075108.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002208/1002208.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002208/1002208.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002208/1002208_cover.png [JournalsId] => 4 [Title] => Exploring the function of myeloid cells in promoting metastasis in head and neck cancer [Abstract] => Head and neck cancer (HNC) is a challenging disease that lacks effective treatment, particularly in the cases that spread locoregionally and metastasize distantly, dramatically reducing patient surv [AbstractComplete] =>Head and neck cancer (HNC) is a challenging disease that lacks effective treatment, particularly in the cases that spread locoregionally and metastasize distantly, dramatically reducing patient survival rates. Expanding the understanding of the mechanisms of the metastatic cascade is critical for creating more effective therapeutics that improve outcomes for HNC patients. A true grasp of cancer metastasis requires the consideration of all cell types that contribute to the inflammatory HNC microenvironment as drivers of this process. More emphasis now is being placed on exploring the roles of the different immune cells in cancer control, tumorigenesis and metastasis. Myeloid cells are the most numerous immune cell types in the body, and they are actively recruited and reprogrammed by tumor cells to behave in a variety of ways. These cells are remarkably diverse in phenotype and function, and the part they play in tumor spread greatly differs based on the cell type. This review will focus on summarizing the roles of macrophages, neutrophils, myeloid derived suppressor cells (MDSCs), and dendritic cells (DCs) in driving HNC metastasis by examining the current knowledge base and offering potential new routes through which to target and treat this deadly process.
[Names] => Dakota Dike Dimegwu Okwuone ... Gregory N. Gan [Doi] => 10.37349/etat.2024.00208 [Published] => February 19, 2024 [Viewed] => 1120 [Downloaded] => 21 [Subject] => Mini Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00208 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 113 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:108–119 [Recommend] => 0 [Keywords] => Head and neck cancer, metastasis, immunology, tumor microenvironment, macrophages, neutrophils, dendritic cells [DetailTitle] => Therapeutic Targeting of the Tumor Microenvironment [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/113 [Id] => 1002208 [ris] => https://www.explorationpub.com/uploads/Article/A1002208/c2183f9ebcb69dd771e544a6e0eeac01.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002208/ac2d3c69c16654b1af2d18f48813b1aa.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Okwuone DDD, Morgan D, Gan GN. Exploring the function of myeloid cells in promoting metastasis in head and neck cancer. Explor Target Antitumor Ther. 2024;5:108–19. https://doi.org/10.37349/etat.2024.00208 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-06 01:56:01 [Bib_Time] => 2024-02-06 01:56:01 [KeysWordContens] => Exploring the function of myeloid cells in promoting metastasis in head and neck cancer, Head and neck cancer, metastasis, immunology, tumor microenvironment, macrophages, neutrophils, dendritic cells, Head and neck cancer (HNC) is a challenging disease that lacks effective treatment, particularly in the cases that spread locoregionally and metastasize distantly, dramatically reducing patient survival rates. Expanding the understanding of the mechanisms of the metastatic cascade is critical for creating more effective therapeutics that improve outcomes for HNC patients. A true grasp of cancer metastasis requires the consideration of all cell types that contribute to the inflammatory HNC microenvironment as drivers of this process. More emphasis now is being placed on exploring the roles of the different immune cells in cancer control, tumorigenesis and metastasis. Myeloid cells are the most numerous immune cell types in the body, and they are actively recruited and reprogrammed by tumor cells to behave in a variety of ways. These cells are remarkably diverse in phenotype and function, and the part they play in tumor spread greatly differs based on the cell type. This review will focus on summarizing the roles of macrophages, neutrophils, myeloid derived suppressor cells (MDSCs), and dendritic cells (DCs) in driving HNC metastasis by examining the current knowledge base and offering potential new routes through which to target and treat this deadly process. ,Dakota Dike Dimegwu Okwuone ... Gregory N. Gan [PublishedText] => Published [IsEdit] => 0 [AccountId] => 87 [Zh] => 1 ) [210] => Array ( [ArticleId] => 1114 [Create_Time] => 2024-02-20 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240228015226.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002209/1002209.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002209/1002209.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002209/1002209-cover.png [JournalsId] => 4 [Title] => The oncogenic role of hepatitis B virus X gene in hepatocarcinogenesis: recent updates [Abstract] => Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancers with high mortality rate. Among its various etiological factors, one of the major risk factors for HCC is a chronic [AbstractComplete] =>Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancers with high mortality rate. Among its various etiological factors, one of the major risk factors for HCC is a chronic infection of hepatitis B virus (HBV). HBV X protein (HBx) has been identified to play an important role in the HBV-induced HCC pathogenesis since it may interfere with several key regulators of many cellular processes. HBx localization within the cells may be beneficial to HBx multiple functions at different phases of HBV infection and associated hepatocarcinogenesis. HBx as a regulatory protein modulates cellular transcription, molecular signal transduction, cell cycle, apoptosis, autophagy, protein degradation pathways, and host genetic stability via interaction with various factors, including its association with various non-coding RNAs. A better understanding on the regulatory mechanism of HBx on various characteristics of HCC would provide an overall picture of HBV-associated HCC. This article addresses recent data on HBx role in the HBV-associated hepatocarcinogenesis.
[Names] => Agustiningsih Agustiningsih ... Caecilia Sukowati [Doi] => 10.37349/etat.2024.00209 [Published] => February 20, 2024 [Viewed] => 502 [Downloaded] => 22 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00209 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 185 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:120–134 [Recommend] => 0 [Keywords] => Hepatitis B virus, hepatitis B virus X protein, hepatocellular carcinoma, signalling pathways [DetailTitle] => Molecular Targeted Therapy for Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/185 [Id] => 1002209 [ris] => https://www.explorationpub.com/uploads/Article/A1002209/7d7997f567380e6c0f130fc330d16baf.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002209/0bd88c520dbcc83c92c0ce56bf936fd6.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Agustiningsih A, Rasyak MR, Turyadi, Jayanti S, Sukowati C. The oncogenic role of hepatitis B virus X gene in hepatocarcinogenesis: recent updates. Explor Target Antitumor Ther. 2024;5:120–34. https://doi.org/10.37349/etat.2024.00209 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-07 01:51:35 [Bib_Time] => 2024-02-07 01:51:35 [KeysWordContens] => The oncogenic role of hepatitis B virus X gene in hepatocarcinogenesis: recent updates, Hepatitis B virus, hepatitis B virus X protein, hepatocellular carcinoma, signalling pathways, Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancers with high mortality rate. Among its various etiological factors, one of the major risk factors for HCC is a chronic infection of hepatitis B virus (HBV). HBV X protein (HBx) has been identified to play an important role in the HBV-induced HCC pathogenesis since it may interfere with several key regulators of many cellular processes. HBx localization within the cells may be beneficial to HBx multiple functions at different phases of HBV infection and associated hepatocarcinogenesis. HBx as a regulatory protein modulates cellular transcription, molecular signal transduction, cell cycle, apoptosis, autophagy, protein degradation pathways, and host genetic stability via interaction with various factors, including its association with various non-coding RNAs. A better understanding on the regulatory mechanism of HBx on various characteristics of HCC would provide an overall picture of HBV-associated HCC. This article addresses recent data on HBx role in the HBV-associated hepatocarcinogenesis. ,Agustiningsih Agustiningsih ... Caecilia Sukowati [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [211] => Array ( [ArticleId] => 1115 [Create_Time] => 2024-02-23 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240223064659.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002210/1002210.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002210/1002210.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002210/1002210_Cover.png [JournalsId] => 4 [Title] => Exploring monocarboxylate transporter inhibition for cancer treatment [Abstract] => Cells are separated from the environment by a lipid bilayer membrane that is relatively impermeable to solutes. The transport of ions and small molecules across this membrane is an essential process [AbstractComplete] =>Cells are separated from the environment by a lipid bilayer membrane that is relatively impermeable to solutes. The transport of ions and small molecules across this membrane is an essential process in cell biology and metabolism. Monocarboxylate transporters (MCTs) belong to a vast family of solute carriers (SLCs) that facilitate the transport of certain hydrophylic small compounds through the bilipid cell membrane. The existence of 446 genes that code for SLCs is the best evidence of their importance. In-depth research on MCTs is quite recent and probably promoted by their role in cancer development and progression. Importantly, it has recently been realized that these transporters represent an interesting target for cancer treatment. The search for clinically useful monocarboxylate inhibitors is an even more recent field. There is limited pre-clinical and clinical experience with new inhibitors and their precise mechanism of action is still under investigation. What is common to all of them is the inhibition of lactate transport. This review discusses the structure and function of MCTs, their participation in cancer, and old and newly developed inhibitors. Some suggestions on how to improve their anticancer effects are also discussed.
[Names] => Tomas Koltai, Larry Fliegel [Doi] => 10.37349/etat.2024.00210 [Published] => February 23, 2024 [Viewed] => 402 [Downloaded] => 22 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00210 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 244 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:135–169 [Recommend] => 0 [Keywords] => Monocarboxylate transporters, glycolytic metabolism, lactate, lactate shuttle, quercetin, diclofenac, AZD3965 [DetailTitle] => Therapeutic Targeting of Tumor Metabolism [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/244 [Id] => 1002210 [ris] => https://www.explorationpub.com/uploads/Article/A1002210/2e8e0fcec458be0899bcf44e0e3deb62.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002210/b6484cde4f371597e63d7db4118b156d.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Koltai T, Fliegel L. Exploring monocarboxylate transporter inhibition for cancer treatment. Explor Target Antitumor Ther. 2024;5:135–69. https://doi.org/10.37349/etat.2024.00210 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-07 02:46:21 [Bib_Time] => 2024-02-07 02:46:21 [KeysWordContens] => Exploring monocarboxylate transporter inhibition for cancer treatment, Monocarboxylate transporters, glycolytic metabolism, lactate, lactate shuttle, quercetin, diclofenac, AZD3965, Cells are separated from the environment by a lipid bilayer membrane that is relatively impermeable to solutes. The transport of ions and small molecules across this membrane is an essential process in cell biology and metabolism. Monocarboxylate transporters (MCTs) belong to a vast family of solute carriers (SLCs) that facilitate the transport of certain hydrophylic small compounds through the bilipid cell membrane. The existence of 446 genes that code for SLCs is the best evidence of their importance. In-depth research on MCTs is quite recent and probably promoted by their role in cancer development and progression. Importantly, it has recently been realized that these transporters represent an interesting target for cancer treatment. The search for clinically useful monocarboxylate inhibitors is an even more recent field. There is limited pre-clinical and clinical experience with new inhibitors and their precise mechanism of action is still under investigation. What is common to all of them is the inhibition of lactate transport. This review discusses the structure and function of MCTs, their participation in cancer, and old and newly developed inhibitors. Some suggestions on how to improve their anticancer effects are also discussed. ,Tomas Koltai, Larry Fliegel [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [212] => Array ( [ArticleId] => 1116 [Create_Time] => 2024-02-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240229064244.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002211/1002211.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002211/1002211.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002211/1002211_Cover.png [JournalsId] => 4 [Title] => Conceptual breakthroughs of the long noncoding RNA functional system and its endogenous regulatory role in the cancerous regime [Abstract] => Long noncoding RNAs (lncRNAs) derived from noncoding regions in the human genome were once regarded as junks with no biological significance, but recent studies have shown that these molecules are h [AbstractComplete] =>Long noncoding RNAs (lncRNAs) derived from noncoding regions in the human genome were once regarded as junks with no biological significance, but recent studies have shown that these molecules are highly functional, prompting an explosion of studies on their biology. However, these recent efforts have only begun to recognize the biological significance of a small fraction (< 1%) of the lncRNAs. The basic concept of these lncRNA functions remains controversial. This controversy arises primarily from conventional biased observations based on limited datasets. Fortunately, emerging big data provides a promising path to circumvent conventional bias to understand an unbiased big picture of lncRNA biology and advance the fundamental principles of lncRNA biology. This review focuses on big data studies that break through the critical concepts of the lncRNA functional system and its endogenous regulatory roles in all cancers. lncRNAs have unique functional systems distinct from proteins, such as transcriptional initiation and regulation, and they abundantly interact with mitochondria and consume less energy. lncRNAs, rather than proteins as traditionally thought, function as the most critical endogenous regulators of all cancers. lncRNAs regulate the cancer regulatory regime by governing the endogenous regulatory network of all cancers. This is accomplished by dominating the regulatory network module and serving as a key hub and top inducer. These critical conceptual breakthroughs lay a blueprint for a comprehensive functional picture of the human genome. They also lay a blueprint for combating human diseases that are regulated by lncRNAs.
[Names] => Anyou Wang [Doi] => 10.37349/etat.2024.00211 [Published] => February 27, 2024 [Viewed] => 435 [Downloaded] => 13 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00211 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:170–186 [Recommend] => 0 [Keywords] => Big data, long noncoding RNA, noncoding RNA, cancer, function, endogenous, regulatory role [DetailTitle] => [DetailUrl] => [Id] => 1002211 [ris] => https://www.explorationpub.com/uploads/Article/A1002211/3c7f0ef48a5447d52ae6d8c78a3ea940.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002211/51d5e85eab239e890a0da8708646e280.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Wang A. Conceptual breakthroughs of the long noncoding RNA functional system and its endogenous regulatory role in the cancerous regime. Explor Target Antitumor Ther. 2024;5:170–86. https://doi.org/10.37349/etat.2024.00211 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-07 02:48:33 [Bib_Time] => 2024-02-07 02:48:33 [KeysWordContens] => Conceptual breakthroughs of the long noncoding RNA functional system and its endogenous regulatory role in the cancerous regime, Big data, long noncoding RNA, noncoding RNA, cancer, function, endogenous, regulatory role, Long noncoding RNAs (lncRNAs) derived from noncoding regions in the human genome were once regarded as junks with no biological significance, but recent studies have shown that these molecules are highly functional, prompting an explosion of studies on their biology. However, these recent efforts have only begun to recognize the biological significance of a small fraction (< 1%) of the lncRNAs. The basic concept of these lncRNA functions remains controversial. This controversy arises primarily from conventional biased observations based on limited datasets. Fortunately, emerging big data provides a promising path to circumvent conventional bias to understand an unbiased big picture of lncRNA biology and advance the fundamental principles of lncRNA biology. This review focuses on big data studies that break through the critical concepts of the lncRNA functional system and its endogenous regulatory roles in all cancers. lncRNAs have unique functional systems distinct from proteins, such as transcriptional initiation and regulation, and they abundantly interact with mitochondria and consume less energy. lncRNAs, rather than proteins as traditionally thought, function as the most critical endogenous regulators of all cancers. lncRNAs regulate the cancer regulatory regime by governing the endogenous regulatory network of all cancers. This is accomplished by dominating the regulatory network module and serving as a key hub and top inducer. These critical conceptual breakthroughs lay a blueprint for a comprehensive functional picture of the human genome. They also lay a blueprint for combating human diseases that are regulated by lncRNAs. ,Anyou Wang [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [213] => Array ( [ArticleId] => 1118 [Create_Time] => 2024-02-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240227035330.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002213/1002213.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002213/1002213.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002213/1002213_cover.png [JournalsId] => 4 [Title] => Recent preclinical and clinical advances in radioimmunotherapy for non-Hodgkin’s lymphoma [Abstract] => Radioimmunotherapy (RIT) is a therapy that combines a radioactive nucleotide with a monoclonal antibody (mAb). RIT enhances the therapeutic effect of mAb and reduces toxicity compared with conventio [AbstractComplete] =>Radioimmunotherapy (RIT) is a therapy that combines a radioactive nucleotide with a monoclonal antibody (mAb). RIT enhances the therapeutic effect of mAb and reduces toxicity compared with conventional treatment. The purpose of this review is to summarize the current progress of RIT for treating non-Hodgkin’s lymphoma (NHL) based on recent preclinical and clinical studies. The efficacy of RIT targeting the B-lymphocyte antigen cluster of differentiation 20 (CD20) has been demonstrated in clinical trials. Two radioimmunoconjugates targeting CD20, yttrium-90 (90Y)-ibritumomab-tiuxetan (Zevalin) and iodine-131 (131I)-tositumomab (Bexxar), have been approved in the USA Food and Drug Administration (FDA) for treating relapsed/refractory indolent or transformed NHL in 2002 and 2003, respectively. Although these two radioimmunoconjugates are effective and least toxic, they have not achieved popularity due to increasing access to novel therapies and the complexity of their delivery process. RIT is constantly evolving with the identification of novel targets and novel therapeutic strategies using newer radionuclides such as alpha-particle isotopes. Alpha-particles show very short path lengths and high linear energy transfer. These characteristics provide increased tumor cell-killing activities and reduced non-specific bystander responses on normal tissue. This review also discusses reviewed pre-targeted RIT (PRIT) and immuno-positron emission tomography (PET). PRIT potentially increases the dose of radionuclide delivered to tumors while toxicities to normal tissues are limited. Immuno-PET is a molecular imaging tracer that combines the high sensitivity of PET with the specific targeting capability of mAb. Immuno-PET strategies targeting CD20 and other antigens are currently being developed. The theragnostic approach by immuno-PET will be useful in monitoring the treatment response.
[Names] => Hiroki Goto ... Seiji Okada [Doi] => 10.37349/etat.2024.00213 [Published] => February 28, 2024 [Viewed] => 523 [Downloaded] => 26 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00213 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 175 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:208–224 [Recommend] => 0 [Keywords] => Radioimmunotherapy, monoclonal antibody, non-Hodgkin’s lymphoma, pre-targeted radioimmunotherapy, immuno-positron emission tomography [DetailTitle] => Novel Strategies and Targets for Immunotherapy of Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/175 [Id] => 1002213 [ris] => https://www.explorationpub.com/uploads/Article/A1002213/17b6b1d9892c777a47afe2dcbfd8ca1b.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002213/790059d4823dcb447cb8a4a915151c9d.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Goto H, Shiraishi Y, Okada S. Recent preclinical and clinical advances in radioimmunotherapy for non-Hodgkin’s lymphoma. Explor Target Antitumor Ther. 2024;5:208–24. https://doi.org/10.37349/etat.2024.00213 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-27 03:53:30 [Bib_Time] => 2024-02-27 03:53:30 [KeysWordContens] => Recent preclinical and clinical advances in radioimmunotherapy for non-Hodgkin’s lymphoma, Radioimmunotherapy, monoclonal antibody, non-Hodgkin’s lymphoma, pre-targeted radioimmunotherapy, immuno-positron emission tomography, Radioimmunotherapy (RIT) is a therapy that combines a radioactive nucleotide with a monoclonal antibody (mAb). RIT enhances the therapeutic effect of mAb and reduces toxicity compared with conventional treatment. The purpose of this review is to summarize the current progress of RIT for treating non-Hodgkin’s lymphoma (NHL) based on recent preclinical and clinical studies. The efficacy of RIT targeting the B-lymphocyte antigen cluster of differentiation 20 (CD20) has been demonstrated in clinical trials. Two radioimmunoconjugates targeting CD20, yttrium-90 (90Y)-ibritumomab-tiuxetan (Zevalin) and iodine-131 (131I)-tositumomab (Bexxar), have been approved in the USA Food and Drug Administration (FDA) for treating relapsed/refractory indolent or transformed NHL in 2002 and 2003, respectively. Although these two radioimmunoconjugates are effective and least toxic, they have not achieved popularity due to increasing access to novel therapies and the complexity of their delivery process. RIT is constantly evolving with the identification of novel targets and novel therapeutic strategies using newer radionuclides such as alpha-particle isotopes. Alpha-particles show very short path lengths and high linear energy transfer. These characteristics provide increased tumor cell-killing activities and reduced non-specific bystander responses on normal tissue. This review also discusses reviewed pre-targeted RIT (PRIT) and immuno-positron emission tomography (PET). PRIT potentially increases the dose of radionuclide delivered to tumors while toxicities to normal tissues are limited. Immuno-PET is a molecular imaging tracer that combines the high sensitivity of PET with the specific targeting capability of mAb. Immuno-PET strategies targeting CD20 and other antigens are currently being developed. The theragnostic approach by immuno-PET will be useful in monitoring the treatment response. ,Hiroki Goto ... Seiji Okada [PublishedText] => Published [IsEdit] => 0 [AccountId] => 77 [Zh] => 1 ) [214] => Array ( [ArticleId] => 1119 [Create_Time] => 2024-02-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240229025512.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002214/1002214.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002214/1002214.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002214/1002214-cover.png [JournalsId] => 4 [Title] => A case of immunotherapy-induced thyroiditis [Abstract] => Immunotherapy treatments for cancer are known to cause adverse thyroid events which present a diagnostic challenge to clinicians and radiologists. This case report highlights the importance of a hig [AbstractComplete] =>Immunotherapy treatments for cancer are known to cause adverse thyroid events which present a diagnostic challenge to clinicians and radiologists. This case report highlights the importance of a high clinical index of suspicion and careful assessment of the thyroid on serial imaging studies to make the diagnosis. The case involves a 65-year-old male with malignant melanoma who was started on immunotherapy as part of a clinical trial. He developed thyroid dysfunction followed by an attack of acute neck pain. Ultrasound of his thyroid was performed which showed significant atrophy. A review of previous imaging was undertaken which confirmed the patient had suffered from thyroiditis and subsequent atrophy. Following this, the diagnosis of immunotherapy-induced thyroid dysfunction was made. Thyroxine supplementation and steroid dose were then adjusted causing his thyroid function and symptoms to improve. Immunotherapy agents for cancers are becoming more and more common. As the case report shows, physicians and radiologists will need to be vigilant to diagnose and treat any adverse events.
[Names] => George Pears ... Joseph Sacco [Doi] => 10.37349/etat.2024.00214 [Published] => February 28, 2024 [Viewed] => 464 [Downloaded] => 21 [Subject] => Case Report [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00214 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 175 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:225–231 [Recommend] => 0 [Keywords] => Immunotherapy, thyroiditis, melanoma, cancer, radiology, endocrinology [DetailTitle] => Novel Strategies and Targets for Immunotherapy of Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/175 [Id] => 1002214 [ris] => https://www.explorationpub.com/uploads/Article/A1002214/39e133b3c9b1eb6f6c7664a2c97515b8.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002214/35716a50a04a61014edb5012405b0923.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Pears G, Mahajan A, Olsson-Brown A, Sacco J. A case of immunotherapy-induced thyroiditis. Explor Target Antitumor Ther. 2024;5:225–31. https://doi.org/10.37349/etat.2024.00214 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-20 01:14:53 [Bib_Time] => 2024-02-20 01:14:53 [KeysWordContens] => A case of immunotherapy-induced thyroiditis, Immunotherapy, thyroiditis, melanoma, cancer, radiology, endocrinology, Immunotherapy treatments for cancer are known to cause adverse thyroid events which present a diagnostic challenge to clinicians and radiologists. This case report highlights the importance of a high clinical index of suspicion and careful assessment of the thyroid on serial imaging studies to make the diagnosis. The case involves a 65-year-old male with malignant melanoma who was started on immunotherapy as part of a clinical trial. He developed thyroid dysfunction followed by an attack of acute neck pain. Ultrasound of his thyroid was performed which showed significant atrophy. A review of previous imaging was undertaken which confirmed the patient had suffered from thyroiditis and subsequent atrophy. Following this, the diagnosis of immunotherapy-induced thyroid dysfunction was made. Thyroxine supplementation and steroid dose were then adjusted causing his thyroid function and symptoms to improve. Immunotherapy agents for cancers are becoming more and more common. As the case report shows, physicians and radiologists will need to be vigilant to diagnose and treat any adverse events. ,George Pears ... Joseph Sacco [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [215] => Array ( [ArticleId] => 1136 [Create_Time] => 2024-02-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240228090757.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002215/1002215.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002215/1002215.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002215/1002215-cover.png [JournalsId] => 4 [Title] => Early-stage triple negative breast cancer: the therapeutic role of immunotherapy and the prognostic value of pathological complete response [Abstract] => Triple negative breast cancer (TNBC) represents an aggressive disease associated with a high risk of recurrence after curative treatment and a poor prognosis in the metastatic setting. Chemotherapy [AbstractComplete] =>Triple negative breast cancer (TNBC) represents an aggressive disease associated with a high risk of recurrence after curative treatment and a poor prognosis in the metastatic setting. Chemotherapy was for years the only treatment available in the early and metastatic setting, due to the lack of actionable targets. Clinical practice has changed following the results obtained with the addition of immunotherapy to standard chemotherapy, the development of novel drugs [i.e. antibody-drug conjugates (ADCs)], and the use of targeted treatments for patients carrying germline pathogenic breast cancer susceptibility genes (BRCA) 1 or BRCA 2 variants. The treatment of early-stage disease has had a shift in clinical practice since July 2021, after the Food and Drug Administration (FDA) approval of pembrolizumab in association with chemotherapy as neoadjuvant treatment for TNBC and as a single agent in the subsequent adjuvant setting. This intensive treatment based on the combination of a poly-chemotherapy and an immune checkpoint inhibitor (ICI) led to the improvement of short- and long-term outcomes, but it has highlighted some new unmet clinical needs in the treatment of early-stage TNBC: the selection of the most effective adjuvant therapy and the integration of pembrolizumab with other therapeutic strategies [capecitabine, poly(ADP-ribose) polymerase (PARP) inhibitors] based on the achievement of pathologic complete response (pCR); the identification of predictive biomarkers to select patients who could most benefit from the addition of ICI, to minimize toxicities and to maximize outcomes; the possibility of de-escalating chemotherapy in favor of immune-combo or novel agents, such as ADCs; the role of immunotherapy in estrogen receptor (ER)-low patients. The advent of immunotherapy not only addresses current challenges in TNBC treatment but also holds the promise of a radical transformation in its therapeutic paradigm, enhancing significantly clinical outcomes and offering new perspectives for patients grappling with this aggressive form of breast cancer.
[Names] => Pierluigi De Santis ... Palma Fedele [Doi] => 10.37349/etat.2024.00215 [Published] => February 28, 2024 [Viewed] => 671 [Downloaded] => 27 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00215 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 137 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:232–250 [Recommend] => 0 [Keywords] => Triple negative breast cancer, immunotherapy, pathological complete response, neoadjuvant combination treatment, adjuvant treatment [DetailTitle] => Innovative Strategies to Target Triple-negative Breast Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/137 [Id] => 1002215 [ris] => https://www.explorationpub.com/uploads/Article/A1002215/09621a9c8229c1717efea76bfd6356df.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002215/2e406b358d2944245f94bfe8bda848b0.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => De Santis P, Perrone M, Guarini C, Santoro AN, Laface C, Carrozzo D, et al. Early-stage triple negative breast cancer: the therapeutic role of immunotherapy and the prognostic value of pathological complete response. Explor Target Antitumor Ther. 2024;5:232–50. https://doi.org/10.37349/etat.2024.00215 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-23 02:47:09 [Bib_Time] => 2024-02-23 02:47:09 [KeysWordContens] => Early-stage triple negative breast cancer: the therapeutic role of immunotherapy and the prognostic value of pathological complete response, Triple negative breast cancer, immunotherapy, pathological complete response, neoadjuvant combination treatment, adjuvant treatment, Triple negative breast cancer (TNBC) represents an aggressive disease associated with a high risk of recurrence after curative treatment and a poor prognosis in the metastatic setting. Chemotherapy was for years the only treatment available in the early and metastatic setting, due to the lack of actionable targets. Clinical practice has changed following the results obtained with the addition of immunotherapy to standard chemotherapy, the development of novel drugs [i.e. antibody-drug conjugates (ADCs)], and the use of targeted treatments for patients carrying germline pathogenic breast cancer susceptibility genes (BRCA) 1 or BRCA 2 variants. The treatment of early-stage disease has had a shift in clinical practice since July 2021, after the Food and Drug Administration (FDA) approval of pembrolizumab in association with chemotherapy as neoadjuvant treatment for TNBC and as a single agent in the subsequent adjuvant setting. This intensive treatment based on the combination of a poly-chemotherapy and an immune checkpoint inhibitor (ICI) led to the improvement of short- and long-term outcomes, but it has highlighted some new unmet clinical needs in the treatment of early-stage TNBC: the selection of the most effective adjuvant therapy and the integration of pembrolizumab with other therapeutic strategies [capecitabine, poly(ADP-ribose) polymerase (PARP) inhibitors] based on the achievement of pathologic complete response (pCR); the identification of predictive biomarkers to select patients who could most benefit from the addition of ICI, to minimize toxicities and to maximize outcomes; the possibility of de-escalating chemotherapy in favor of immune-combo or novel agents, such as ADCs; the role of immunotherapy in estrogen receptor (ER)-low patients. The advent of immunotherapy not only addresses current challenges in TNBC treatment but also holds the promise of a radical transformation in its therapeutic paradigm, enhancing significantly clinical outcomes and offering new perspectives for patients grappling with this aggressive form of breast cancer. ,Pierluigi De Santis ... Palma Fedele [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [216] => Array ( [ArticleId] => 1171 [Create_Time] => 2024-03-08 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240423081222.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002216/1002216.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002216/1002216.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002216/1002216_cover.png [JournalsId] => 4 [Title] => Potential of targeting signal-transducing adaptor protein-2 in cancer therapeutic applications [Abstract] => Adaptor proteins play essential roles in various intracellular signaling pathways. Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein that possesses pleckstrin homology (PH) and Src [AbstractComplete] =>Adaptor proteins play essential roles in various intracellular signaling pathways. Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein that possesses pleckstrin homology (PH) and Src homology 2 (SH2) domains, as well as a YXXQ signal transducer and activator of transcription 3 (STAT3)-binding motif in its C-terminal region. STAP-2 is also a substrate of breast tumor kinase (BRK). STAP-2/BRK expression is deregulated in breast cancers and enhances STAT3-dependent cell proliferation. In prostate cancer cells, STAP-2 interacts with and stabilizes epidermal growth factor receptor (EGFR) after stimulation, resulting in the upregulation of EGFR signaling, which contributes to cancer-cell proliferation and tumor progression. Therefore, inhibition of the interaction between STAP-2 and BRK/EGFR may be a possible therapeutic strategy for these cancers. For this purpose, peptides that interfere with STAP-2/BRK/EGFR binding may have great potential. Indeed, the identified peptide inhibitor successfully suppressed the STAP-2/EGFR protein interaction, EGFR stabilization, and cancer-cell growth. Furthermore, the peptide inhibitor suppressed tumor formation in human prostate- and lung-cancer cell lines in a murine xenograft model. This review focuses on the inhibitory peptide as a promising candidate for the treatment of prostate and lung cancers.
[Names] => Taiga Maemoto ... Tadashi Matsuda [Doi] => 10.37349/etat.2024.00216 [Published] => March 07, 2024 [Viewed] => 303 [Downloaded] => 17 [Subject] => Mini Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00216 [Inline] => 1 [Type] => 0 [Issue] => [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:251–259 [Recommend] => 0 [Keywords] => Signal-transducing adaptor protein, signal transduction, epidermal growth factor receptor, prostate cancer, lung cancer, peptides [DetailTitle] => [DetailUrl] => [Id] => 1002216 [ris] => https://www.explorationpub.com/uploads/Article/A1002216/d8528f4cd651a58377fe3c507c375e1c.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002216/fa8d0241fea253faf3ada351c6d84b4f.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Maemoto T, Sasaki Y, Okuyama F, Kitai Y, Oritani K, Matsuda T. Potential of targeting signal-transducing adaptor protein-2 in cancer therapeutic applications. Explor Target Antitumor Ther. 2024;5:251–9. https://doi.org/10.37349/etat.2024.00216 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-03-04 07:09:23 [Bib_Time] => 2024-03-04 07:09:23 [KeysWordContens] => Potential of targeting signal-transducing adaptor protein-2 in cancer therapeutic applications, Signal-transducing adaptor protein, signal transduction, epidermal growth factor receptor, prostate cancer, lung cancer, peptides, Adaptor proteins play essential roles in various intracellular signaling pathways. Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein that possesses pleckstrin homology (PH) and Src homology 2 (SH2) domains, as well as a YXXQ signal transducer and activator of transcription 3 (STAT3)-binding motif in its C-terminal region. STAP-2 is also a substrate of breast tumor kinase (BRK). STAP-2/BRK expression is deregulated in breast cancers and enhances STAT3-dependent cell proliferation. In prostate cancer cells, STAP-2 interacts with and stabilizes epidermal growth factor receptor (EGFR) after stimulation, resulting in the upregulation of EGFR signaling, which contributes to cancer-cell proliferation and tumor progression. Therefore, inhibition of the interaction between STAP-2 and BRK/EGFR may be a possible therapeutic strategy for these cancers. For this purpose, peptides that interfere with STAP-2/BRK/EGFR binding may have great potential. Indeed, the identified peptide inhibitor successfully suppressed the STAP-2/EGFR protein interaction, EGFR stabilization, and cancer-cell growth. Furthermore, the peptide inhibitor suppressed tumor formation in human prostate- and lung-cancer cell lines in a murine xenograft model. This review focuses on the inhibitory peptide as a promising candidate for the treatment of prostate and lung cancers. ,Taiga Maemoto ... Tadashi Matsuda [PublishedText] => Published [IsEdit] => 0 [AccountId] => 22 [Zh] => 1 ) [217] => Array ( [ArticleId] => 1175 [Create_Time] => 2024-03-21 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240424014323.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002217/1002217.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002217/1002217.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002217/1002217_cover.png [JournalsId] => 4 [Title] => Improving the quality of patient care in lung cancer: key factors for successful multidisciplinary team working [Abstract] => International Guidelines as well as Cancer Associations recommend a multidisciplinary approach to lung cancer care. A multidisciplinary team (MDT) can significantly improve treatment decision-making [AbstractComplete] =>International Guidelines as well as Cancer Associations recommend a multidisciplinary approach to lung cancer care. A multidisciplinary team (MDT) can significantly improve treatment decision-making and patient coordination by putting different physicians and other health professionals “in the same room”, who collectively decide upon the best possible treatment. However, this is not a panacea for cancer treatment. The impact of multidisciplinary care (MDC) on patient outcomes is not univocal, while the effective functioning of the MDT depends on many factors. This review presents the available MDT literature with an emphasis on the key factors that characterize high-quality patient care in lung cancer. The study was conducted with a bibliographic search using different electronic databases (PubMed Central, Scopus, Google Scholar, and Google) referring to multidisciplinary cancer care settings. Many key elements appear consolidated, while others emerge as prevalent and actual, especially those related to visible barriers which work across geographic, organizational, and disciplinary boundaries. MDTs must be sustained by strategic management, structured within the entity, and cannot be managed as a separate care process. Furthermore, they need to coordinate with other teams (within and outside the organization) and join with the broad range of services delivered by multiple providers at various points of the cancer journey or within the system, with the vision of integrated care.
[Names] => Alessandro Morabito ... Giacomo Pascarella [Doi] => 10.37349/etat.2024.00217 [Published] => March 21, 2024 [Viewed] => 280 [Downloaded] => 19 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00217 [Inline] => 1 [Type] => 0 [Issue] => [Topic] => 126 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:260–277 [Recommend] => 0 [Keywords] => Multidisciplinary team care, multidisciplinary clinic model, multi-team system, care pathway [DetailTitle] => Integrated Approaches for Non-Small-Cell Lung Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/126 [Id] => 1002217 [ris] => https://www.explorationpub.com/uploads/Article/A1002217/37a263c71b5a71436a06a56976b7ae3c.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002217/58233bcd0740bc0c927877cd358e9c85.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Morabito A, Mercadante E, Muto P, Manzo A, Palumbo G, Sforza V, et al. Improving the quality of patient care in lung cancer: key factors for successful multidisciplinary team working. Explor Target Antitumor Ther. 2024;5:260–77. https://doi.org/10.37349/etat.2024.00217 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-03-15 01:59:35 [Bib_Time] => 2024-03-15 01:59:35 [KeysWordContens] => Improving the quality of patient care in lung cancer: key factors for successful multidisciplinary team working, Multidisciplinary team care, multidisciplinary clinic model, multi-team system, care pathway, International Guidelines as well as Cancer Associations recommend a multidisciplinary approach to lung cancer care. A multidisciplinary team (MDT) can significantly improve treatment decision-making and patient coordination by putting different physicians and other health professionals “in the same room”, who collectively decide upon the best possible treatment. However, this is not a panacea for cancer treatment. The impact of multidisciplinary care (MDC) on patient outcomes is not univocal, while the effective functioning of the MDT depends on many factors. This review presents the available MDT literature with an emphasis on the key factors that characterize high-quality patient care in lung cancer. The study was conducted with a bibliographic search using different electronic databases (PubMed Central, Scopus, Google Scholar, and Google) referring to multidisciplinary cancer care settings. Many key elements appear consolidated, while others emerge as prevalent and actual, especially those related to visible barriers which work across geographic, organizational, and disciplinary boundaries. MDTs must be sustained by strategic management, structured within the entity, and cannot be managed as a separate care process. Furthermore, they need to coordinate with other teams (within and outside the organization) and join with the broad range of services delivered by multiple providers at various points of the cancer journey or within the system, with the vision of integrated care. ,Alessandro Morabito ... Giacomo Pascarella [PublishedText] => Published [IsEdit] => 0 [AccountId] => 57 [Zh] => 1 ) [218] => Array ( [ArticleId] => 1176 [Create_Time] => 2024-03-22 [zipUrl] => https://www.explorationpub.com/uploads/zip/202403/20240327013752.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002218/1002218.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002218/1002218.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002218/1002218-cover.png [JournalsId] => 4 [Title] => Hexachlorobenzene as a differential modulator of the conventional and metronomic chemotherapy response in triple negative breast cancer cells [Abstract] => Aim: Triple negative breast cancer (TNBC) is usually treated with high doses of paclitaxel, whose effectiveness may be modulated by the action of environmental contaminants such as hexachlorobenz [AbstractComplete] =>Triple negative breast cancer (TNBC) is usually treated with high doses of paclitaxel, whose effectiveness may be modulated by the action of environmental contaminants such as hexachlorobenzene. High doses of paclitaxel cause adverse effects such as low cellular selectivity and the generation of resistance to treatment due to an increase in the expression of multidrug resistance proteins (MRPs). These effects can be reduced using a metronomic administration scheme with low doses. This study aimed to investigate whether hexachlorobenzene modulates the response of cells to conventional chemotherapy with paclitaxel or metronomic chemotherapy with paclitaxel plus carbachol, as well as to study the participation of the MRP ATP-binding cassette transporter G2 (ABCG2) in human TNBC MDA-MB231 cells.
Cells were treated with hexachlorobenzene alone or in combination with conventional or metronomic chemotherapies. The effects of treatments on cell viability were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the nuclear factor kappa B pathway participation was evaluated using a selective inhibitor. ABCG2 expression and its modulation were determined by western blot.
Results confirmed that paclitaxel reduces MDA-MB231 cell viability in a concentration-dependent manner. Results also showed that both conventional and metronomic chemotherapies reduced cell viability with similar efficacy. Although hexachlorobenzene did not modify cell viability per se, it did reverse the effect induced by the conventional chemotherapy, without affecting the efficacy of the metronomic chemotherapy. Additionally, a differential modulation of ABCG2 expression was determined, mediated by the nuclear factor kappa B pathway, which was directly related to the modulation of cell sensitivity to another cycle of paclitaxel treatment.
The findings indicate that, in human TNBC MDA-MB231 cells, in the presence of hexachlorobenzene, the metronomic combination of paclitaxel plus carbachol is more effective in affecting the tumor biology than the conventional therapeutic administration scheme of paclitaxel.
Innate lymphoid cells (ILCs) are the most recently discovered class of innate immune cells found to have prominent roles in various human immune-related pathologies such as infection and autoimmune diseases. However, their role in cancer was largely unclear until recently, where several emerging studies over the past few years unanimously demonstrate ILCs to be critical players in tumour immunity. Being the innate counterpart of T cells, ILCs are potent cytokine producers through which they orchestrate the overall immune response upstream of adaptive immunity thereby modulating T cell function. Out of the major ILC subsets, ILC1s have gained significant traction as potential immunotherapeutic candidates due to their central involvement with the anti-tumour type 1 immune response. ILC1s are potent producers of the well-established anti-tumour cytokine interferon γ (IFNγ), and exert direct cytotoxicity against cancer cells in response to the cytokine interleukin-15 (IL-15). However, in advanced diseases, ILC1s are found to demonstrate an exhausted phenotype in the tumour microenvironment (TME) with impaired effector functions, characterised by decreased responsiveness to cytokines and reduced IFNγ production. Tumour cells produce immunomodulatory cytokines such as transforming growth factor β (TGFβ) and IL-23, and through these suppress ILC1 anti-tumour actfivities and converts ILC1s to pro-tumoural ILC3s respectively, resulting in disease progression. This review provides a comprehensive overview of ILC1s in tumour immunity, and discusses the exciting prospects of harnessing ILC1s for cancer immunotherapy, either alone or in combination with cytokine-based treatment. The exciting prospects of targeting the upstream innate immune system through ILC1s may surmount the limitations associated with adaptive immune T cell-based strategies used in the clinic currently, and overcome cancer immunotherapeutic resistance.
[Names] => James Michael Verner ... Eric Jou [Doi] => 10.37349/etat.2023.00219 [Published] => April 23, 2024 [Viewed] => 105 [Downloaded] => 8 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00219 [Inline] => 1 [Type] => 0 [Issue] => 2 [Topic] => 216 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:296–315 [Recommend] => 0 [Keywords] => Innate lymphoid cells, type 1 innate lymphoid cells, cytokines, innate immunity, tumour microenvironment, cancer therapy, preclinical models, immunotherapy [DetailTitle] => Novel Insights into Immunotherapy Targeting Tumor Microenvironment in Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/216 [Id] => 1002219 [ris] => https://www.explorationpub.com/uploads/Article/A1002219/a7c445970e4b1a2bf8329a617d8b223c.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002219/96b3c512435d0ca5a4dc29aaa6ecac13.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Verner JM, Arbuthnott HF, Ramachandran R, Bharadwaj M, Chaudhury N, Jou E. Emerging roles of type 1 innate lymphoid cells in tumour pathogenesis and cancer immunotherapy. Explor Target Antitumor Ther. 2023;5:296–315. https://doi.org/10.37349/etat.2024.00219 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-19 01:36:56 [Bib_Time] => 2024-04-19 01:36:56 [KeysWordContens] => Emerging roles of type 1 innate lymphoid cells in tumour pathogenesis and cancer immunotherapy, Innate lymphoid cells, type 1 innate lymphoid cells, cytokines, innate immunity, tumour microenvironment, cancer therapy, preclinical models, immunotherapy, Innate lymphoid cells (ILCs) are the most recently discovered class of innate immune cells found to have prominent roles in various human immune-related pathologies such as infection and autoimmune diseases. However, their role in cancer was largely unclear until recently, where several emerging studies over the past few years unanimously demonstrate ILCs to be critical players in tumour immunity. Being the innate counterpart of T cells, ILCs are potent cytokine producers through which they orchestrate the overall immune response upstream of adaptive immunity thereby modulating T cell function. Out of the major ILC subsets, ILC1s have gained significant traction as potential immunotherapeutic candidates due to their central involvement with the anti-tumour type 1 immune response. ILC1s are potent producers of the well-established anti-tumour cytokine interferon γ (IFNγ), and exert direct cytotoxicity against cancer cells in response to the cytokine interleukin-15 (IL-15). However, in advanced diseases, ILC1s are found to demonstrate an exhausted phenotype in the tumour microenvironment (TME) with impaired effector functions, characterised by decreased responsiveness to cytokines and reduced IFNγ production. Tumour cells produce immunomodulatory cytokines such as transforming growth factor β (TGFβ) and IL-23, and through these suppress ILC1 anti-tumour actfivities and converts ILC1s to pro-tumoural ILC3s respectively, resulting in disease progression. This review provides a comprehensive overview of ILC1s in tumour immunity, and discusses the exciting prospects of harnessing ILC1s for cancer immunotherapy, either alone or in combination with cytokine-based treatment. The exciting prospects of targeting the upstream innate immune system through ILC1s may surmount the limitations associated with adaptive immune T cell-based strategies used in the clinic currently, and overcome cancer immunotherapeutic resistance. ,James Michael Verner ... Eric Jou [PublishedText] => Published [IsEdit] => 0 [AccountId] => 46 [Zh] => 1 ) [220] => Array ( [ArticleId] => 1184 [Create_Time] => 2024-04-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240424030924.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002221/1002221.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002221/1002221.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002221/1002221_cover.png [JournalsId] => 4 [Title] => Artificial intelligence and classification of mature lymphoid neoplasms [Abstract] => Hematologists, geneticists, and clinicians came to a multidisciplinary agreement on the classification of lymphoid neoplasms that combines clinical features, histological characteristics, immunophen [AbstractComplete] =>Hematologists, geneticists, and clinicians came to a multidisciplinary agreement on the classification of lymphoid neoplasms that combines clinical features, histological characteristics, immunophenotype, and molecular pathology analyses. The current classification includes the World Health Organization (WHO) Classification of tumours of haematopoietic and lymphoid tissues revised 4th edition, the International Consensus Classification (ICC) of mature lymphoid neoplasms (report from the Clinical Advisory Committee 2022), and the 5th edition of the proposed WHO Classification of haematolymphoid tumours (lymphoid neoplasms, WHO-HAEM5). This article revises the recent advances in the classification of mature lymphoid neoplasms. Artificial intelligence (AI) has advanced rapidly recently, and its role in medicine is becoming more important as AI integrates computer science and datasets to make predictions or classifications based on complex input data. Summarizing previous research, it is described how several machine learning and neural networks can predict the prognosis of the patients, and classified mature B-cell neoplasms. In addition, new analysis predicted lymphoma subtypes using cell-of-origin markers that hematopathologists use in the clinical routine, including CD3, CD5, CD19, CD79A, MS4A1 (CD20), MME (CD10), BCL6, IRF4 (MUM-1), BCL2, SOX11, MNDA, and FCRL4 (IRTA1). In conclusion, although most categories are similar in both classifications, there are also conceptual differences and differences in the diagnostic criteria for some diseases. It is expected that AI will be incorporated into the lymphoma classification as another bioinformatics tool.
[Names] => Joaquim Carreras ... Naoya Nakamura [Doi] => 10.37349/etat.2024.00221 [Published] => April 23, 2024 [Viewed] => 67 [Downloaded] => 6 [Subject] => Perspective [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00221 [Inline] => 1 [Type] => 0 [Issue] => [Topic] => 88 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:332–348 [Recommend] => 0 [Keywords] => Artificial intelligence, machine learning, deep learning, artificial neural networks, non-Hodgkin lymphomas, pan-cancer series, prognosis, gene expression [DetailTitle] => Artificial Intelligence for Precision Oncology [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/88 [Id] => 1002221 [ris] => https://www.explorationpub.com/uploads/Article/A1002221/6683e519c65c1bbc03b771b5938a95f7.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002221/37d2062053460a42c51220c07e9df7f5.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Carreras J, Hamoudi R, Nakamura N. Artificial intelligence and classification of mature lymphoid neoplasms. Explor Target Antitumor Ther. 2024;5:332–48. https://doi.org/10.37349/etat.2024.00221 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-24 03:09:24 [Bib_Time] => 2024-04-24 03:09:24 [KeysWordContens] => Artificial intelligence and classification of mature lymphoid neoplasms, Artificial intelligence, machine learning, deep learning, artificial neural networks, non-Hodgkin lymphomas, pan-cancer series, prognosis, gene expression, Hematologists, geneticists, and clinicians came to a multidisciplinary agreement on the classification of lymphoid neoplasms that combines clinical features, histological characteristics, immunophenotype, and molecular pathology analyses. The current classification includes the World Health Organization (WHO) Classification of tumours of haematopoietic and lymphoid tissues revised 4th edition, the International Consensus Classification (ICC) of mature lymphoid neoplasms (report from the Clinical Advisory Committee 2022), and the 5th edition of the proposed WHO Classification of haematolymphoid tumours (lymphoid neoplasms, WHO-HAEM5). This article revises the recent advances in the classification of mature lymphoid neoplasms. Artificial intelligence (AI) has advanced rapidly recently, and its role in medicine is becoming more important as AI integrates computer science and datasets to make predictions or classifications based on complex input data. Summarizing previous research, it is described how several machine learning and neural networks can predict the prognosis of the patients, and classified mature B-cell neoplasms. In addition, new analysis predicted lymphoma subtypes using cell-of-origin markers that hematopathologists use in the clinical routine, including CD3, CD5, CD19, CD79A, MS4A1 (CD20), MME (CD10), BCL6, IRF4 (MUM-1), BCL2, SOX11, MNDA, and FCRL4 (IRTA1). In conclusion, although most categories are similar in both classifications, there are also conceptual differences and differences in the diagnostic criteria for some diseases. It is expected that AI will be incorporated into the lymphoma classification as another bioinformatics tool. ,Joaquim Carreras ... Naoya Nakamura [PublishedText] => Published [IsEdit] => 0 [AccountId] => 77 [Zh] => 1 ) [221] => Array ( [ArticleId] => 1185 [Create_Time] => 2024-04-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240426052045.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002222/1002222.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002222/1002222.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002222/1002222-cover.png [JournalsId] => 4 [Title] => Tumor metabolism in pheochromocytomas: clinical and therapeutic implications [Abstract] => Pheochromocytomas and paragangliomas (PPGLs) have emerged as one of the most common endocrine tumors. It epitomizes fascinating crossroads of genetic, metabolic, and endocrine oncology, providing a [AbstractComplete] =>Pheochromocytomas and paragangliomas (PPGLs) have emerged as one of the most common endocrine tumors. It epitomizes fascinating crossroads of genetic, metabolic, and endocrine oncology, providing a canvas to explore the molecular intricacies of tumor biology. Predominantly rooted in the aberration of metabolic pathways, particularly the Krebs cycle and related enzymatic functionalities, PPGLs manifest an intriguing metabolic profile, highlighting elevated levels of oncometabolites like succinate and fumarate, and furthering cellular malignancy and genomic instability. This comprehensive review aims to delineate the multifaceted aspects of tumor metabolism in PPGLs, encapsulating genetic factors, oncometabolites, and potential therapeutic avenues, thereby providing a cohesive understanding of metabolic disturbances and their ramifications in tumorigenesis and disease progression. Initial investigations into PPGLs metabolomics unveiled a stark correlation between specific genetic mutations, notably in the succinate dehydrogenase complex (SDHx) genes, and the accumulation of oncometabolites, establishing a pivotal role in epigenetic alterations and hypoxia-inducible pathways. By scrutinizing voluminous metabolic studies and exploiting technologies, novel insights into the metabolic and genetic aspects of PPGLs are perpetually being gathered elucidating complex interactions and molecular machinations. Additionally, the exploration of therapeutic strategies targeting metabolic abnormalities has burgeoned harboring potential for innovative and efficacious treatment modalities. This review encapsulates the profound metabolic complexities of PPGLs, aiming to foster an enriched understanding and pave the way for future investigations and therapeutic innovations in managing these metabolically unique tumors.
[Names] => Mohammad Sadiq Jeeyavudeen ... Joseph M. Pappachan [Doi] => 10.37349/etat.2024.00222 [Published] => April 24, 2024 [Viewed] => 70 [Downloaded] => 5 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00222 [Inline] => 1 [Type] => 0 [Issue] => [Topic] => 217 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:349–373 [Recommend] => 0 [Keywords] => Pheochromocytoma, tumor metabolism, metabolomics, gene mutations, metanephrines [DetailTitle] => Recent Approaches in Tumor Metabolism [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/217 [Id] => 1002222 [ris] => https://www.explorationpub.com/uploads/Article/A1002222/d7d78ca2f4f93e312e02c42c7c77c529.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002222/e26c40656c25dba27fe0292c91e2ebbb.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Jeeyavudeen MS, Mathiyalagan N, Fernandez James C, Pappachan JM. Tumor metabolism in pheochromocytomas: clinical and therapeutic implications. Explor Target Antitumor Ther. 2024;5:349–73. https://doi.org/10.37349/etat.2024.00222 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-03-26 01:15:02 [Bib_Time] => 2024-03-26 01:15:02 [KeysWordContens] => Tumor metabolism in pheochromocytomas: clinical and therapeutic implications, Pheochromocytoma, tumor metabolism, metabolomics, gene mutations, metanephrines, Pheochromocytomas and paragangliomas (PPGLs) have emerged as one of the most common endocrine tumors. It epitomizes fascinating crossroads of genetic, metabolic, and endocrine oncology, providing a canvas to explore the molecular intricacies of tumor biology. Predominantly rooted in the aberration of metabolic pathways, particularly the Krebs cycle and related enzymatic functionalities, PPGLs manifest an intriguing metabolic profile, highlighting elevated levels of oncometabolites like succinate and fumarate, and furthering cellular malignancy and genomic instability. This comprehensive review aims to delineate the multifaceted aspects of tumor metabolism in PPGLs, encapsulating genetic factors, oncometabolites, and potential therapeutic avenues, thereby providing a cohesive understanding of metabolic disturbances and their ramifications in tumorigenesis and disease progression. Initial investigations into PPGLs metabolomics unveiled a stark correlation between specific genetic mutations, notably in the succinate dehydrogenase complex (SDHx) genes, and the accumulation of oncometabolites, establishing a pivotal role in epigenetic alterations and hypoxia-inducible pathways. By scrutinizing voluminous metabolic studies and exploiting technologies, novel insights into the metabolic and genetic aspects of PPGLs are perpetually being gathered elucidating complex interactions and molecular machinations. Additionally, the exploration of therapeutic strategies targeting metabolic abnormalities has burgeoned harboring potential for innovative and efficacious treatment modalities. This review encapsulates the profound metabolic complexities of PPGLs, aiming to foster an enriched understanding and pave the way for future investigations and therapeutic innovations in managing these metabolically unique tumors. ,Mohammad Sadiq Jeeyavudeen ... Joseph M. Pappachan [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [222] => Array ( [ArticleId] => 1186 [Create_Time] => 2024-04-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240424034542.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002223/1002223.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002223/1002223.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002223/1002223-cover.png [JournalsId] => 4 [Title] => Improving single nucleotide polymorphisms genotyping accuracy for dihydropyrimidine dehydrogenase testing in pharmacogenetics [Abstract] => Fluoropyrimidines, crucial in cancer treatment, often cause toxicity concerns even at standard doses. Toxic accumulation of fluoropyrimidine metabolites, culminating in adverse effects, can stem fro [AbstractComplete] =>Fluoropyrimidines, crucial in cancer treatment, often cause toxicity concerns even at standard doses. Toxic accumulation of fluoropyrimidine metabolites, culminating in adverse effects, can stem from impaired dihydropyrimidine dehydrogenase (DPYD) enzymatic function. Emerging evidence underscores the role of single nucleotide polymorphisms (SNPs) in DPYD gene, capable of inducing DPYD activity deficiency. Consequently, DPYD genotyping’s importance is on the rise in clinical practice before initiating fluoropyrimidine treatment. Although polymerase chain reaction (PCR) followed by Sanger sequencing (SS; PCR-SS) is a prevalent method for DPYD genotyping, it may encounter limitations. In this context, there is reported a case in which a routine PCR-SS approach for genotyping DPYD SNP rs55886062 failed in a proband of African descent. The Clinical Pharmacogenetics Implementation Consortium (CPIC) categorizes the guanine (G) allele of this SNP as non-functional. The enforcement of whole genome sequencing (WGS) approach led to the identification of two adenine (A) insertions near the PCR primers annealing regions in the proband, responsible for a sequence frameshift and a genotyping error for rs55886062. These SNPs (rs145228578, 1-97981199-T-TA and rs141050810, 1-97981622-G-GA) were extremely rare in non-Finnish Europeans (0.05%) but prevalent in African populations (16%). Although limited evidence was available for these SNPs, they were catalogued as benign variants in public databases. Notably, these two SNPs exhibited a high linkage disequilibrium [LD; squared correlation coefficient (R2) = 0.98]. These findings highlighted the importance to consider the prevalence of genetic variants within diverse ethnic populations when designing primers and probes for SNP genotyping in pharmacogenetic testing. This preventive measure is essential to avoid sequence frameshifts or primer misalignments arising from SNP occurrences in the genome, which can compromise PCR-SS and lead to genotyping failures. Furthermore, this case highlights the significance of exploring alternative genotyping approaches, like WGS, when confronted with challenges associated with conventional techniques.
[Names] => Annalaura Montella ... Mario Capasso [Doi] => 10.37349/etat.2024.00223 [Published] => April 24, 2024 [Viewed] => 66 [Downloaded] => 7 [Subject] => Case Report [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00223 [Inline] => 1 [Type] => 0 [Issue] => [Topic] => 209 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:374–383 [Recommend] => 0 [Keywords] => Pharmacogenetics, dihydropyrimidine dehydrogenase, genotyping [DetailTitle] => Molecular Diagnosis and Personalized Therapy of Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/209 [Id] => 1002223 [ris] => https://www.explorationpub.com/uploads/Article/A1002223/6384f61df8fb722dc52e7b9067c00897.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002223/918d1f91b7fa53a89b83b022c1d5dca3.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Montella A, Cantalupo S, D’Alterio G, Damiano V, Iolascon A, Capasso M. Improving single nucleotide polymorphisms genotyping accuracy for dihydropyrimidine dehydrogenase testing in pharmacogenetics. Explor Target Antitumor Ther. 2024;5:374–83. https://doi.org/10.37349/etat.2024.00223 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-03-26 01:19:22 [Bib_Time] => 2024-03-26 01:19:22 [KeysWordContens] => Improving single nucleotide polymorphisms genotyping accuracy for dihydropyrimidine dehydrogenase testing in pharmacogenetics, Pharmacogenetics, dihydropyrimidine dehydrogenase, genotyping, Fluoropyrimidines, crucial in cancer treatment, often cause toxicity concerns even at standard doses. Toxic accumulation of fluoropyrimidine metabolites, culminating in adverse effects, can stem from impaired dihydropyrimidine dehydrogenase (DPYD) enzymatic function. Emerging evidence underscores the role of single nucleotide polymorphisms (SNPs) in DPYD gene, capable of inducing DPYD activity deficiency. Consequently, DPYD genotyping’s importance is on the rise in clinical practice before initiating fluoropyrimidine treatment. Although polymerase chain reaction (PCR) followed by Sanger sequencing (SS; PCR-SS) is a prevalent method for DPYD genotyping, it may encounter limitations. In this context, there is reported a case in which a routine PCR-SS approach for genotyping DPYD SNP rs55886062 failed in a proband of African descent. The Clinical Pharmacogenetics Implementation Consortium (CPIC) categorizes the guanine (G) allele of this SNP as non-functional. The enforcement of whole genome sequencing (WGS) approach led to the identification of two adenine (A) insertions near the PCR primers annealing regions in the proband, responsible for a sequence frameshift and a genotyping error for rs55886062. These SNPs (rs145228578, 1-97981199-T-TA and rs141050810, 1-97981622-G-GA) were extremely rare in non-Finnish Europeans (0.05%) but prevalent in African populations (16%). Although limited evidence was available for these SNPs, they were catalogued as benign variants in public databases. Notably, these two SNPs exhibited a high linkage disequilibrium [LD; squared correlation coefficient (R2) = 0.98]. These findings highlighted the importance to consider the prevalence of genetic variants within diverse ethnic populations when designing primers and probes for SNP genotyping in pharmacogenetic testing. This preventive measure is essential to avoid sequence frameshifts or primer misalignments arising from SNP occurrences in the genome, which can compromise PCR-SS and lead to genotyping failures. Furthermore, this case highlights the significance of exploring alternative genotyping approaches, like WGS, when confronted with challenges associated with conventional techniques. ,Annalaura Montella ... Mario Capasso [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [223] => Array ( [ArticleId] => 1209 [Create_Time] => 2024-04-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240426074905.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002224/1002224.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002224/1002224.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002224/1002224_cover.png [JournalsId] => 4 [Title] => Alteration of glucose metabolism and expression of glucose transporters in ovarian cancer [Abstract] => Aerobic glycolysis also known as the Warburg effect, remains a hallmark of various cancers, including ovarian cancer. Cancer cells undergo metabolic changes to sustain their tumorigenic properties a [AbstractComplete] =>Aerobic glycolysis also known as the Warburg effect, remains a hallmark of various cancers, including ovarian cancer. Cancer cells undergo metabolic changes to sustain their tumorigenic properties and adapt to environmental conditions, such as hypoxia and nutrient starvation. Altered metabolic pathways not only facilitate ovarian cancer cells’ survival and proliferation but also endow them to metastasize, develop resistance to chemotherapy, maintain cancer stem cell phenotype, and escape anti-tumor immune responses. Glucose transporters (GLUTs), which play a pivotal role as the rate-limiting step in glycolysis, are frequently overexpressed in a variety of tumors, including ovarian cancer. Multiple oncoproteins can regulate GLUT proteins, promoting tumor proliferation, migration, and metastasis, either dependent or independent of glycolysis. This review examines the alteration of GLUT proteins, particularly GLUT1, in ovarian cancer and its impact on cancer initiation, progression, and resistance to treatment. Additionally, it highlights the role of these proteins as biomarkers for diagnosis and prognosis in ovarian cancer, and delves into novel therapeutic strategies currently under development that target GLUT isoforms.
[Names] => Fatima Ben Ali ... Rabii Ameziane El Hassani [Doi] => 10.37349/etat.2024.00224 [Published] => April 24, 2024 [Viewed] => 69 [Downloaded] => 7 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00224 [Inline] => 1 [Type] => 0 [Issue] => [Topic] => 217 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:384–399 [Recommend] => 0 [Keywords] => Ovarian cancer, glucose transporters, aerobic glycolysis, diagnosis biomarker, prognosis biomarker, chemotherapy resistance [DetailTitle] => Recent Approaches in Tumor Metabolism [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/217 [Id] => 1002224 [ris] => https://www.explorationpub.com/uploads/Article/A1002224/eba87302002c11e0f9075142daad7b60.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002224/7283cea37ed36383b3669646f4e8b1f4.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Ben Ali F, Qmichou Z, Oukabli M, Dakka N, Bakri Y, Eddouks M, et al. Alteration of glucose metabolism and expression of glucose transporters in ovarian cancer. Explor Target Antitumor Ther. 2024;5:384–99. https://doi.org/10.37349/etat.2024.00224 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-26 07:49:05 [Bib_Time] => 2024-04-26 07:49:05 [KeysWordContens] => Alteration of glucose metabolism and expression of glucose transporters in ovarian cancer, Ovarian cancer, glucose transporters, aerobic glycolysis, diagnosis biomarker, prognosis biomarker, chemotherapy resistance, Aerobic glycolysis also known as the Warburg effect, remains a hallmark of various cancers, including ovarian cancer. Cancer cells undergo metabolic changes to sustain their tumorigenic properties and adapt to environmental conditions, such as hypoxia and nutrient starvation. Altered metabolic pathways not only facilitate ovarian cancer cells’ survival and proliferation but also endow them to metastasize, develop resistance to chemotherapy, maintain cancer stem cell phenotype, and escape anti-tumor immune responses. Glucose transporters (GLUTs), which play a pivotal role as the rate-limiting step in glycolysis, are frequently overexpressed in a variety of tumors, including ovarian cancer. Multiple oncoproteins can regulate GLUT proteins, promoting tumor proliferation, migration, and metastasis, either dependent or independent of glycolysis. This review examines the alteration of GLUT proteins, particularly GLUT1, in ovarian cancer and its impact on cancer initiation, progression, and resistance to treatment. Additionally, it highlights the role of these proteins as biomarkers for diagnosis and prognosis in ovarian cancer, and delves into novel therapeutic strategies currently under development that target GLUT isoforms. ,Fatima Ben Ali ... Rabii Ameziane El Hassani [PublishedText] => Published [IsEdit] => 0 [AccountId] => 77 [Zh] => 1 ) [224] => Array ( [ArticleId] => 1210 [Create_Time] => 2024-04-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240424064909.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002225/1002225.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002225/1002225.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002225/1002225_cover.png [JournalsId] => 4 [Title] => Cancer symptom cluster research in pediatric oncology: a work in progress [Abstract] => In the 21st century, advances in basic research have provided new insights in the field of pediatric oncology. Pediatric patients tend to experience higher levels of distressing symptoms, which toge [AbstractComplete] =>In the 21st century, advances in basic research have provided new insights in the field of pediatric oncology. Pediatric patients tend to experience higher levels of distressing symptoms, which together form a symptom cluster. In clinical practice, these symptom clusters are reported daily by children and adolescents with cancer. Translational research has emerged as the translation of new knowledge from basic science into clinical practice. Understanding how neuroimmunoendocrine pathways regulate cancer development and the aspects underlying the specific therapies, such as chemotherapy and immunotherapy, is an important frontier for future research in pediatric oncology. The goal of translational research is to show how different variables in tumor and patient characteristics explain the differential effects of interventions, as translational research provides new insights into the management of cancer symptoms in children and adolescents with cancer. Together, this approach could lead to improvements in pediatric oncology care worldwide.
[Names] => Luciana Chain Veronez, Luís Carlos Lopes-Júnior [Doi] => 10.37349/etat.2024.00225 [Published] => April 24, 2024 [Viewed] => 64 [Downloaded] => 6 [Subject] => Perspective [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00225 [Inline] => 1 [Type] => 0 [Issue] => 0 [Topic] => 0 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:400–408 [Recommend] => 0 [Keywords] => Cancer symptom clusters, pediatric oncology, translational research [DetailTitle] => [DetailUrl] => [Id] => 1002225 [ris] => https://www.explorationpub.com/uploads/Article/A1002225/26d5e0388ef8eefc737a8bba28a04249.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002225/6b15a83b4350c1b6a95cdf93bac18ee6.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Veronez LC, Lopes-Júnior LC. Cancer symptom cluster research in pediatric oncology: a work in progress. Explor Target Antitumor Ther. 2024;5:400–8. https://doi.org/10.37349/etat.2024.00225 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-03 07:15:09 [Bib_Time] => 2024-04-03 07:15:09 [KeysWordContens] => Cancer symptom cluster research in pediatric oncology: a work in progress, Cancer symptom clusters, pediatric oncology, translational research, In the 21st century, advances in basic research have provided new insights in the field of pediatric oncology. Pediatric patients tend to experience higher levels of distressing symptoms, which together form a symptom cluster. In clinical practice, these symptom clusters are reported daily by children and adolescents with cancer. Translational research has emerged as the translation of new knowledge from basic science into clinical practice. Understanding how neuroimmunoendocrine pathways regulate cancer development and the aspects underlying the specific therapies, such as chemotherapy and immunotherapy, is an important frontier for future research in pediatric oncology. The goal of translational research is to show how different variables in tumor and patient characteristics explain the differential effects of interventions, as translational research provides new insights into the management of cancer symptoms in children and adolescents with cancer. Together, this approach could lead to improvements in pediatric oncology care worldwide. ,Luciana Chain Veronez, Luís Carlos Lopes-Júnior [PublishedText] => Published [IsEdit] => 0 [AccountId] => 87 [Zh] => 1 ) [225] => Array ( [ArticleId] => 1213 [Create_Time] => 2024-04-25 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240425072753.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002226/1002226.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002226/1002226.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002226/1002226-cover.png [JournalsId] => 4 [Title] => Spheroids and organoids derived from colorectal cancer as tools for in vitro drug screening [Abstract] => Colorectal cancer (CRC) is a heterogeneous disease. Conventional two-dimensional (2D) culture employing cell lines was developed to study the molecular properties of CRC in vitro. Although these cel [AbstractComplete] =>Colorectal cancer (CRC) is a heterogeneous disease. Conventional two-dimensional (2D) culture employing cell lines was developed to study the molecular properties of CRC in vitro. Although these cell lines which are isolated from the tumor niche in which cancer develop, the translation to human model such as studying drug response is often hindered by the inability of cell lines to recapture original tumor features and the lack of heterogeneous clinical tumors represented by this 2D model, differed from in vivo condition. These limitations which may be overcome by utilizing three-dimensional (3D) culture consisting of spheroids and organoids. Over the past decade, great advancements have been made in optimizing culture method to establish spheroids and organoids of solid tumors including of CRC for multiple purposes including drug screening and establishing personalized medicine. These structures have been proven to be versatile and robust models to study CRC progression and deciphering its heterogeneity. This review will describe on advances in 3D culture technology and the application as well as the challenges of CRC-derived spheroids and organoids as a mode to screen for anticancer drugs.
[Names] => Sahira Syamimi Ahmad Zawawi ... Marahaini Musa [Doi] => 10.37349/etat.2024.00226 [Published] => April 25, 2024 [Viewed] => 69 [Downloaded] => 8 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.00226 [Inline] => 1 [Type] => 0 [Issue] => 0 [Topic] => 98 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:409–431 [Recommend] => 0 [Keywords] => Organoid, colon cancer, drug screening [DetailTitle] => Emerging Screening Technologies in Drug Discovery [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/98 [Id] => 1002226 [ris] => https://www.explorationpub.com/uploads/Article/A1002226/2c665a43e33e0c5474c0df55e8d3c48d.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002226/5ed4b586628718ee478318ec57e95194.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Ahmad Zawawi SS, Salleh EA, Musa M. Spheroids and organoids derived from colorectal cancer as tools for in vitro drug screening. Explor Target Antitumor Ther. 2024;5:409–31. https://doi.org/10.37349/etat.2024.00226 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-03 07:55:16 [Bib_Time] => 2024-04-03 07:55:16 [KeysWordContens] => Spheroids and organoids derived from colorectal cancer as tools for in vitro drug screening, Organoid, colon cancer, drug screening, Colorectal cancer (CRC) is a heterogeneous disease. Conventional two-dimensional (2D) culture employing cell lines was developed to study the molecular properties of CRC in vitro. Although these cell lines which are isolated from the tumor niche in which cancer develop, the translation to human model such as studying drug response is often hindered by the inability of cell lines to recapture original tumor features and the lack of heterogeneous clinical tumors represented by this 2D model, differed from in vivo condition. These limitations which may be overcome by utilizing three-dimensional (3D) culture consisting of spheroids and organoids. Over the past decade, great advancements have been made in optimizing culture method to establish spheroids and organoids of solid tumors including of CRC for multiple purposes including drug screening and establishing personalized medicine. These structures have been proven to be versatile and robust models to study CRC progression and deciphering its heterogeneity. This review will describe on advances in 3D culture technology and the application as well as the challenges of CRC-derived spheroids and organoids as a mode to screen for anticancer drugs. ,Sahira Syamimi Ahmad Zawawi ... Marahaini Musa [PublishedText] => Published [IsEdit] => 0 [AccountId] => 76 [Zh] => 1 ) [226] => Array ( [ArticleId] => 1226 [Create_Time] => 2024-04-26 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240426054024.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A1002227/1002227.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A1002227/1002227.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A1002227/1002227_cover.png [JournalsId] => 4 [Title] => Tri-specific killer engager: unleashing multi-synergic power against cancer [Abstract] => Cancer continues to be a global health concern, necessitating innovative solutions for treatment. Tri-specific killer engagers (TriKEs) have emerged as a promising class of immunotherapeutic agents, [AbstractComplete] =>Cancer continues to be a global health concern, necessitating innovative solutions for treatment. Tri-specific killer engagers (TriKEs) have emerged as a promising class of immunotherapeutic agents, offering a multifaceted approach to cancer treatment. TriKEs simultaneously engage and activate natural killer (NK) cells while specifically targeting cancer cells, representing an outstanding advancement in immunotherapy. This review explores the generation and mechanisms of TriKEs, highlighting their advantages over other immunotherapies and discussing their potential impact on clinical trials and cancer treatment. TriKEs are composed of three distinct domains, primarily antibody-derived building blocks, linked together by short amino acid sequences. They incorporate critical elements, anti-cluster of differentiation 16 (CD16) and interleukin-15 (IL-15), which activate and enhance NK cell function, together with specific antibody to target each cancer. TriKEs exhibit remarkable potential in preclinical and early clinical studies across various cancer types, making them a versatile tool in cancer immunotherapy. Comparative analyses with other immunotherapies, such as chimeric antigen receptor-T (CAR-T) cell therapy, immune checkpoint inhibitors (ICIs), cytokine therapies, and monoclonal antibodies (mAbs), reveal the unique advantages of TriKEs. They offer a safer pathway for immunotherapy by targeting cancer cells without hyperactivating T cells, reducing off-target effects and complications. The future of TriKEs involves addressing challenges related to dosing, tumor-associated antigen (TAA) expression, and NK cell suppression. Researchers are exploring innovative dosing strategies, enhancing specificity through tumor-specific antigens (TSAs), and combining TriKEs with other therapies for increased efficacy.
[Names] => Peeranut Winidmanokul ... Seiji Okada [Doi] => 10.37349/etat.2024.00227 [Published] => April 25, 2024 [Viewed] => 87 [Downloaded] => 6 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/etat.2024.002227 [Inline] => 1 [Type] => 0 [Issue] => 2 [Topic] => 175 [TitleAbbr] => Explor Target Antitumor Ther. [Pages] => 2024;5:432–448 [Recommend] => 0 [Keywords] => Tri-specific killer engager, natural killer cell, immunotherapy, cancer [DetailTitle] => Novel Strategies and Targets for Immunotherapy of Cancer [DetailUrl] => https://www.explorationpub.com/Journals/etat/Special_Issues/175 [Id] => 1002227 [ris] => https://www.explorationpub.com/uploads/Article/A1002227/93ef673f5b94c3c4ec5c4c16136295ba.ris [bib] => https://www.explorationpub.com/uploads/Article/A1002227/3800dfdcbc35dbdbcbb03c9245b78818.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Winidmanokul P, Panya A, Okada S. Tri-specific killer engager: unleashing multi-synergic power against cancer. Explor Target Antitumor Ther. 2024;5:432–48. https://doi.org/10.37349/etat.2024.00227 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-11 05:27:43 [Bib_Time] => 2024-04-12 01:59:47 [KeysWordContens] => Tri-specific killer engager: unleashing multi-synergic power against cancer, Tri-specific killer engager, natural killer cell, immunotherapy, cancer, Cancer continues to be a global health concern, necessitating innovative solutions for treatment. Tri-specific killer engagers (TriKEs) have emerged as a promising class of immunotherapeutic agents, offering a multifaceted approach to cancer treatment. TriKEs simultaneously engage and activate natural killer (NK) cells while specifically targeting cancer cells, representing an outstanding advancement in immunotherapy. This review explores the generation and mechanisms of TriKEs, highlighting their advantages over other immunotherapies and discussing their potential impact on clinical trials and cancer treatment. TriKEs are composed of three distinct domains, primarily antibody-derived building blocks, linked together by short amino acid sequences. They incorporate critical elements, anti-cluster of differentiation 16 (CD16) and interleukin-15 (IL-15), which activate and enhance NK cell function, together with specific antibody to target each cancer. TriKEs exhibit remarkable potential in preclinical and early clinical studies across various cancer types, making them a versatile tool in cancer immunotherapy. Comparative analyses with other immunotherapies, such as chimeric antigen receptor-T (CAR-T) cell therapy, immune checkpoint inhibitors (ICIs), cytokine therapies, and monoclonal antibodies (mAbs), reveal the unique advantages of TriKEs. They offer a safer pathway for immunotherapy by targeting cancer cells without hyperactivating T cells, reducing off-target effects and complications. The future of TriKEs involves addressing challenges related to dosing, tumor-associated antigen (TAA) expression, and NK cell suppression. Researchers are exploring innovative dosing strategies, enhancing specificity through tumor-specific antigens (TSAs), and combining TriKEs with other therapies for increased efficacy. ,Peeranut Winidmanokul ... Seiji Okada [PublishedText] => Published [IsEdit] => 0 [AccountId] => 87 [Zh] => 0 ) )