Liquid biopsy (LB) is a complex of procedures aimed at the detection of tumor-derived fragments (nucleic acids, proteins, cells, etc.) persisting in the blood or other body fluids. It can be utilized for early cancer diagnosis, analysis of biomarkers of tumor drug sensitivity and prognosis, monitoring of minimal residual disease (MRD), etc. Circulating tumor DNA (ctDNA) is an accessible and reliable LB analyte as it may contain tumor-specific mutations and is amenable to efficient detection by next-generation sequencing (NGS) or droplet digital PCR (ddPCR). High level of ctDNA is typically associated with increased tumor burden and poor prognosis, whereas treatment-related ctDNA clearance increases the probability of a favorable disease outcome. Major efforts have been invested in enhancing the analytical performance of ctDNA detection. Stimulation of apoptosis of tumor cells by irradiation of cancer lumps has been shown to result in a transient but modest increase in ctDNA concentration. There are several sophisticated modifications of ultra-deep NGS protocols, which discriminate between “true” low-copy mutation-specific signals and sequencing artifacts. Slowing physiological ctDNA decay by interfering with liver macrophages and circulating nucleases has shown promise in animal experiments. Reproducibility of ctDNA-based LB assays remains insufficient for samples with ultra-low content of ctDNA; hence, interlaboratory harmonization of ctDNA testing procedures is of paramount importance.
Liquid biopsy (LB) is a complex of procedures aimed at the detection of tumor-derived fragments (nucleic acids, proteins, cells, etc.) persisting in the blood or other body fluids. It can be utilized for early cancer diagnosis, analysis of biomarkers of tumor drug sensitivity and prognosis, monitoring of minimal residual disease (MRD), etc. Circulating tumor DNA (ctDNA) is an accessible and reliable LB analyte as it may contain tumor-specific mutations and is amenable to efficient detection by next-generation sequencing (NGS) or droplet digital PCR (ddPCR). High level of ctDNA is typically associated with increased tumor burden and poor prognosis, whereas treatment-related ctDNA clearance increases the probability of a favorable disease outcome. Major efforts have been invested in enhancing the analytical performance of ctDNA detection. Stimulation of apoptosis of tumor cells by irradiation of cancer lumps has been shown to result in a transient but modest increase in ctDNA concentration. There are several sophisticated modifications of ultra-deep NGS protocols, which discriminate between “true” low-copy mutation-specific signals and sequencing artifacts. Slowing physiological ctDNA decay by interfering with liver macrophages and circulating nucleases has shown promise in animal experiments. Reproducibility of ctDNA-based LB assays remains insufficient for samples with ultra-low content of ctDNA; hence, interlaboratory harmonization of ctDNA testing procedures is of paramount importance.
DOI: https://doi.org/10.37349/etat.2025.1002333
This article belongs to the special issue Liquid Biopsy: Has Already Changed the Clinical Decision-Making in Solid Tumors Treatment?
Aim:
Angiogenesis, invasion, and tube formation are critical processes in tumor progression and metastasis. The use of nanoparticles derived from natural products presents a promising approach for targeted cancer therapy. This study evaluates the anti-angiogenic and anti-invasive effects of Moringa oleifera silver nanoparticles (MO-AgNPs) as a therapeutic strategy against these processes.
Methods:
The anti-angiogenic and anti-invasive activities of MO-AgNPs were investigated using a series of in vitro and ex vivo models. These included the rat aortic ring assay, endothelial tube formation assay, cell invasion assay using endothelial cell lines (Ea.hy926), and a three-dimensional (3D) co-culture spheroid model to simulate tumor microenvironment behavior. Comparisons were made with known inhibitors: quercetin (15.11 μg/mL) and suramin (100 μg/mL).
Results:
MO-AgNPs at 12 μg/mL significantly inhibited Ea.hy926 cell invasion by 62.10% and significantly suppressed endothelial tube formation, comparable to the effect of quercetin. In the ex vivo aortic ring assay, MO-AgNPs reduced microvessel sprouting by 83.824 ± 0.081%, surpassing the inhibition achieved by suramin. Additionally, in the 3D spheroid model, MO-AgNPs at concentrations of 12 μg/mL and 6 μg/mL, as well as quercetin, significantly reduced spheroid diameter by day 14, indicating suppressed invasive potential and angiogenic support.
Conclusions:
MO-AgNPs exhibit strong anti-angiogenic and anti-invasive effects across various tumor-relevant models, highlighting their potential as a therapeutic agent against tumor progression and angiogenesis-related diseases. These results support further investigation of MO-AgNPs as a novel nanotherapeutic for cancer treatment.
Aim:
Angiogenesis, invasion, and tube formation are critical processes in tumor progression and metastasis. The use of nanoparticles derived from natural products presents a promising approach for targeted cancer therapy. This study evaluates the anti-angiogenic and anti-invasive effects of Moringa oleifera silver nanoparticles (MO-AgNPs) as a therapeutic strategy against these processes.
Methods:
The anti-angiogenic and anti-invasive activities of MO-AgNPs were investigated using a series of in vitro and ex vivo models. These included the rat aortic ring assay, endothelial tube formation assay, cell invasion assay using endothelial cell lines (Ea.hy926), and a three-dimensional (3D) co-culture spheroid model to simulate tumor microenvironment behavior. Comparisons were made with known inhibitors: quercetin (15.11 μg/mL) and suramin (100 μg/mL).
Results:
MO-AgNPs at 12 μg/mL significantly inhibited Ea.hy926 cell invasion by 62.10% and significantly suppressed endothelial tube formation, comparable to the effect of quercetin. In the ex vivo aortic ring assay, MO-AgNPs reduced microvessel sprouting by 83.824 ± 0.081%, surpassing the inhibition achieved by suramin. Additionally, in the 3D spheroid model, MO-AgNPs at concentrations of 12 μg/mL and 6 μg/mL, as well as quercetin, significantly reduced spheroid diameter by day 14, indicating suppressed invasive potential and angiogenic support.
Conclusions:
MO-AgNPs exhibit strong anti-angiogenic and anti-invasive effects across various tumor-relevant models, highlighting their potential as a therapeutic agent against tumor progression and angiogenesis-related diseases. These results support further investigation of MO-AgNPs as a novel nanotherapeutic for cancer treatment.
DOI: https://doi.org/10.37349/etat.2025.1002332
This article belongs to the special issue Molecular Mechanisms and Intervention Options in Metastatic Spread of Cancer
Aim:
Clinico-pathological features have traditionally guided prognosis and adjuvant therapy for breast cancer (BC) patients. In the past decade, genomic tests such as Oncotype DX entered clinical practice to refine risk stratification and predict chemotherapy benefit for hormone-receptor positive (HR+)/human epidermal growth factor-receptor 2 negative (HER2–) BC patients after surgery. This is a retrospective analysis to investigate the correlation between histopathological parameters and recurrence score (RS), accounting for menopausal status.
Methods:
Data on HR+/HER2– early BC patients who underwent Oncotype DX were collected using an institutional database. Clinico-pathological characteristics were retrieved. Linear regression was used with RS as a continuous outcome, while logistic regression was performed for pre- and post-menopausal patients, dichotomizing RS at thresholds of 16 and 25, respectively.
Results:
A total of 180 women were included (35% pre-menopausal, 65% post-menopausal). Median age was 57.5 years. Most patients had pT1, pN0, G2 BC, with median estrogen receptor (ER) expression of 95% and a median Ki67 of 25%. Median RS was 16 [interquartile range (IQR) 12–22] in the overall cohort, 15 in pre-menopausal, and 17 in post-menopausal women. In the entire cohort, RS significantly correlated with G3 (P = 0.01), Ki67% (P < 0.0001), ER% (P = 0.03), and progesterone receptor (PgR)% (P < 0.0001). In pre-menopausal patients, only Ki67% (P = 0.02), ER% (P = 0.01), and PgR% (P < 0.0001) showed significant correlations, while in post-menopausal patients, G3 (P = 0.03), Ki67% (P = 0.001), and PgR% (P < 0.0001) achieved statistical significance. Logistic regression analysis showed that in pre-menopausal patients, PgR% predicted RS > 16 [odds ratio (OR) 0.95, P = 0.001]. In post-menopausal women, Ki67% (OR 1.08, P = 0.031) and PgR% (OR 0.95, P < 0.0001) predicted RS > 25.
Conclusions:
In this patient cohort, classical clinico-pathological features showed varying correlations with RS, depending on menopausal status. These findings highlight the complexity of risk stratification, suggesting that further research is needed to better understand the factors influencing RS and its clinical utility.
Aim:
Clinico-pathological features have traditionally guided prognosis and adjuvant therapy for breast cancer (BC) patients. In the past decade, genomic tests such as Oncotype DX entered clinical practice to refine risk stratification and predict chemotherapy benefit for hormone-receptor positive (HR+)/human epidermal growth factor-receptor 2 negative (HER2–) BC patients after surgery. This is a retrospective analysis to investigate the correlation between histopathological parameters and recurrence score (RS), accounting for menopausal status.
Methods:
Data on HR+/HER2– early BC patients who underwent Oncotype DX were collected using an institutional database. Clinico-pathological characteristics were retrieved. Linear regression was used with RS as a continuous outcome, while logistic regression was performed for pre- and post-menopausal patients, dichotomizing RS at thresholds of 16 and 25, respectively.
Results:
A total of 180 women were included (35% pre-menopausal, 65% post-menopausal). Median age was 57.5 years. Most patients had pT1, pN0, G2 BC, with median estrogen receptor (ER) expression of 95% and a median Ki67 of 25%. Median RS was 16 [interquartile range (IQR) 12–22] in the overall cohort, 15 in pre-menopausal, and 17 in post-menopausal women. In the entire cohort, RS significantly correlated with G3 (P = 0.01), Ki67% (P < 0.0001), ER% (P = 0.03), and progesterone receptor (PgR)% (P < 0.0001). In pre-menopausal patients, only Ki67% (P = 0.02), ER% (P = 0.01), and PgR% (P < 0.0001) showed significant correlations, while in post-menopausal patients, G3 (P = 0.03), Ki67% (P = 0.001), and PgR% (P < 0.0001) achieved statistical significance. Logistic regression analysis showed that in pre-menopausal patients, PgR% predicted RS > 16 [odds ratio (OR) 0.95, P = 0.001]. In post-menopausal women, Ki67% (OR 1.08, P = 0.031) and PgR% (OR 0.95, P < 0.0001) predicted RS > 25.
Conclusions:
In this patient cohort, classical clinico-pathological features showed varying correlations with RS, depending on menopausal status. These findings highlight the complexity of risk stratification, suggesting that further research is needed to better understand the factors influencing RS and its clinical utility.
DOI: https://doi.org/10.37349/etat.2025.1002331
This article belongs to the special issue Predictive and Prognostic Biomarkers in Cancer: Towards the Precision Medicine Era
Aim:
This study aimed at the identification of new druggable alterations in non-small cell lung carcinomas (NSCLCs).
Methods:
RNA next generation sequencing (NGS) analysis for 650 protein kinase genes was performed for 89 NSCLCs obtained from young-onset and/or female non-smokers, who were negative for activating events involving EGFR, ALK, ROS1, RET, MET, NTRK1/2/3, BRAF, HER2, KRAS, or NRAS genes.
Results:
RNA sequencing identified 32 in-frame rearrangements, including 9 instances of fully preserved and 8 tumors with partially preserved tyrosine kinase domains. These 17 translocations were further analyzed in 1,059 mutation-negative NSCLCs, which resulted in the identification of two additional tumors with ADK::KAT6B rearrangement and one carcinoma carrying RPS6KB1::VMP1 fusion. The recently reported CLIP1::LTK gene fusion was tested in 2,754 NSCLCs, which were negative for all known actionable mutations, however, no new instances of this translocation have been observed. We further analyzed RNA sequencing results of 89 NSCLCs for mutations affecting the kinase domain of the involved gene. There were 53 substitutions with a combined annotation dependent depletion (CADD) score above 25; all these lesions turned out to be unique, as the analysis of 551 additional NSCLCs revealed no recurrent alterations. ROS1, LTK, and FGFR4 high-level overexpression was observed in 1 out of 89 tumors each.
Conclusions:
This study demonstrates the scarcity of yet unknown kinase-activating alterations in NSCLCs.
Aim:
This study aimed at the identification of new druggable alterations in non-small cell lung carcinomas (NSCLCs).
Methods:
RNA next generation sequencing (NGS) analysis for 650 protein kinase genes was performed for 89 NSCLCs obtained from young-onset and/or female non-smokers, who were negative for activating events involving EGFR, ALK, ROS1, RET, MET, NTRK1/2/3, BRAF, HER2, KRAS, or NRAS genes.
Results:
RNA sequencing identified 32 in-frame rearrangements, including 9 instances of fully preserved and 8 tumors with partially preserved tyrosine kinase domains. These 17 translocations were further analyzed in 1,059 mutation-negative NSCLCs, which resulted in the identification of two additional tumors with ADK::KAT6B rearrangement and one carcinoma carrying RPS6KB1::VMP1 fusion. The recently reported CLIP1::LTK gene fusion was tested in 2,754 NSCLCs, which were negative for all known actionable mutations, however, no new instances of this translocation have been observed. We further analyzed RNA sequencing results of 89 NSCLCs for mutations affecting the kinase domain of the involved gene. There were 53 substitutions with a combined annotation dependent depletion (CADD) score above 25; all these lesions turned out to be unique, as the analysis of 551 additional NSCLCs revealed no recurrent alterations. ROS1, LTK, and FGFR4 high-level overexpression was observed in 1 out of 89 tumors each.
Conclusions:
This study demonstrates the scarcity of yet unknown kinase-activating alterations in NSCLCs.
DOI: https://doi.org/10.37349/etat.2025.1002330
Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States. Emerging evidence highlights the significant role of gut microbiota dysbiosis, characterized by a reduction in beneficial bacteria and an increase in pro-inflammatory and pro-carcinogenic bacteria, in CRC pathogenesis. Both genetic and environmental factors, including diet, antibiotic use, physical activity, aging, and obesity, contribute to this microbial imbalance. Dysbiosis promotes chronic inflammation and immune dysregulation, which facilitates tumor initiation and progression. This review examines the intricate interactions between gut microbiota, immune modulation, and CRC development. It explores current and emerging therapeutic strategies that target the microbiome to enhance treatment efficacy, discusses interventions aimed at restoring healthy microbiota in CRC patients, and outlines future directions for microbiome-based therapies to improve clinical outcomes.
Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States. Emerging evidence highlights the significant role of gut microbiota dysbiosis, characterized by a reduction in beneficial bacteria and an increase in pro-inflammatory and pro-carcinogenic bacteria, in CRC pathogenesis. Both genetic and environmental factors, including diet, antibiotic use, physical activity, aging, and obesity, contribute to this microbial imbalance. Dysbiosis promotes chronic inflammation and immune dysregulation, which facilitates tumor initiation and progression. This review examines the intricate interactions between gut microbiota, immune modulation, and CRC development. It explores current and emerging therapeutic strategies that target the microbiome to enhance treatment efficacy, discusses interventions aimed at restoring healthy microbiota in CRC patients, and outlines future directions for microbiome-based therapies to improve clinical outcomes.
DOI: https://doi.org/10.37349/etat.2025.1002329
Biliary tract cancers (BTCs) are aggressive malignancies associated with poor prognosis and limited treatment options. Advances in precision oncology, notably the identification of recurrent molecular alterations such as fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, ERBB2 amplifications, and v-Raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutations, have introduced new therapeutic avenues and modest survival benefits for patients with advanced disease. However, the practical implementation of targeted therapies remains hampered by challenges in tumor tissue acquisition and molecular testing, highlighting the need for alternative genomic profiling strategies. This comprehensive review examines the role of liquid biopsy as a non-invasive strategy for molecular profiling in BTCs, with a focus on the clinical applications of plasma and bile-derived circulating tumor DNA (ctDNA). We synthesized findings from recent clinical studies evaluating mutation detection rates, concordance between liquid biopsy and tissue-based assays, and the comparative performance of plasma versus bile ctDNA. Liquid biopsy demonstrates high rates of mutation detection and good concordance with tissue analyses. Bile-derived ctDNA, owing to its proximity to the tumor, consistently shows higher sensitivity and mutant allele frequencies (MAFs) than plasma ctDNA. Nevertheless, challenges remain, including lower sensitivity for detecting structural alterations (e.g., gene fusions), variability in ctDNA yield depending on disease status, and a lack of assay standardization across platforms. Liquid biopsy, particularly through bile ctDNA analysis, emerges as a promising adjunct to tissue biopsy for molecular profiling in BTCs. It offers opportunities for earlier, less invasive, and more personalized treatment decisions. Future directions should aim at developing tumor-informed liquid biopsy strategies that increase precision, reduce costs, and ultimately improve patient outcomes. Prospective studies are needed to confirm its clinical utility and survival impact.
Biliary tract cancers (BTCs) are aggressive malignancies associated with poor prognosis and limited treatment options. Advances in precision oncology, notably the identification of recurrent molecular alterations such as fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, ERBB2 amplifications, and v-Raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutations, have introduced new therapeutic avenues and modest survival benefits for patients with advanced disease. However, the practical implementation of targeted therapies remains hampered by challenges in tumor tissue acquisition and molecular testing, highlighting the need for alternative genomic profiling strategies. This comprehensive review examines the role of liquid biopsy as a non-invasive strategy for molecular profiling in BTCs, with a focus on the clinical applications of plasma and bile-derived circulating tumor DNA (ctDNA). We synthesized findings from recent clinical studies evaluating mutation detection rates, concordance between liquid biopsy and tissue-based assays, and the comparative performance of plasma versus bile ctDNA. Liquid biopsy demonstrates high rates of mutation detection and good concordance with tissue analyses. Bile-derived ctDNA, owing to its proximity to the tumor, consistently shows higher sensitivity and mutant allele frequencies (MAFs) than plasma ctDNA. Nevertheless, challenges remain, including lower sensitivity for detecting structural alterations (e.g., gene fusions), variability in ctDNA yield depending on disease status, and a lack of assay standardization across platforms. Liquid biopsy, particularly through bile ctDNA analysis, emerges as a promising adjunct to tissue biopsy for molecular profiling in BTCs. It offers opportunities for earlier, less invasive, and more personalized treatment decisions. Future directions should aim at developing tumor-informed liquid biopsy strategies that increase precision, reduce costs, and ultimately improve patient outcomes. Prospective studies are needed to confirm its clinical utility and survival impact.
DOI: https://doi.org/10.37349/etat.2025.1002328
This article belongs to the special issue Liquid Biopsy: Has Already Changed the Clinical Decision-Making in Solid Tumors Treatment?
Fibroblast growth factor receptor 1 (FGFR1) plays a critical role in the progression of various cancers through its involvement in cell proliferation, survival, and differentiation. More recently, FGFR1 has been implicated in the mechanisms of immune evasion, particularly its role in resistance to immune checkpoint inhibitors (ICIs) such as pembrolizumab and nivolumab. Targeting FGFR1 with monoclonal antibodies and tyrosine kinase inhibitors has emerged as a promising therapeutic strategy to enhance ICI efficacy by altering the tumor microenvironment and countering immune suppression. Preclinical studies demonstrate that combining FGFR1 inhibitors, such as the novel monoclonal antibody OM-RCA-01, with ICIs significantly improves antitumor activity, enhancing T cell responses and cytokine production. This article explores the role of FGFR1 in cancer biology, its contribution to immunotherapy resistance, and the therapeutic potential of targeting FGFR1 to enhance the efficacy of ICIs.
Fibroblast growth factor receptor 1 (FGFR1) plays a critical role in the progression of various cancers through its involvement in cell proliferation, survival, and differentiation. More recently, FGFR1 has been implicated in the mechanisms of immune evasion, particularly its role in resistance to immune checkpoint inhibitors (ICIs) such as pembrolizumab and nivolumab. Targeting FGFR1 with monoclonal antibodies and tyrosine kinase inhibitors has emerged as a promising therapeutic strategy to enhance ICI efficacy by altering the tumor microenvironment and countering immune suppression. Preclinical studies demonstrate that combining FGFR1 inhibitors, such as the novel monoclonal antibody OM-RCA-01, with ICIs significantly improves antitumor activity, enhancing T cell responses and cytokine production. This article explores the role of FGFR1 in cancer biology, its contribution to immunotherapy resistance, and the therapeutic potential of targeting FGFR1 to enhance the efficacy of ICIs.
DOI: https://doi.org/10.37349/etat.2025.1002327
Aim:
BRCA1/2-associated breast and ovarian carcinomas are often regarded as a single entity, assuming that BRCA1 and BRCA2 genes are almost equivalent with regard to their clinical significance. However, BRCA1 and BRCA2 genes differ in their function; therefore, a comparison of treatment outcomes in BRCA1 vs. BRCA2 carriers is warranted.
Methods:
This study focused on consecutive patients treated with neoadjuvant chemotherapy (NACT), given that these subjects are treatment-naive and accessible for immediate assessment of pathological and clinical outcomes.
Results:
BRCA2-associated high-grade serous ovarian carcinomas (HGSOCs) demonstrated significantly higher rates of pathologic complete response (pCR) as compared to BRCA1-related cancers [8/15 (53%) vs. 7/48 (15%), P = 0.004]. In contrast, HER2-negative breast cancer (BC) patients showed a numerically higher rate of pCR in BRCA1 vs. BRCA2 mutation carriers [38/69 (55%) vs. 13/36 (36%), P = 0.1]. However, the comparison with BRCA-wild-type (WT) tumors revealed that this tendency was mainly attributed to the increased prevalence of hormone receptor (HR)-negative disease in the former group. When BC patients were stratified according to the tumor receptor status, the response rates in triple-negative patients were consistently higher than in HR+/HER2– patients across all analyzed subgroups [BRCA1: 35/59 (59%) vs. 3/10 (30%); BRCA2: 5/10 (50%) vs. 8/26 (31%); WT: 31/76 (41%) vs. 12/74 (16%); Mantel-Haenzsel P < 0.001]. Logistic regression analysis revealed that the odds ratio (OR) for achieving pCR was higher for receptor status (triple-negative vs. HR+: OR = 3.4, 95% CI 1.9–6.0, P < 0.001) than for BRCA status (any mutation vs. WT: OR = 2.1, 95% CI 1.2–3.6, P = 0.008). The addition of carboplatin did not improve pCR rates in BRCA1- or BRCA2-associated BCs, while there was a numerically higher efficacy of carboplatin-containing regimens in patients with WT triple-negative tumors [14/26 (54%) vs. 15/44 (34%), P = 0.13].
Conclusions:
Hereditary ovarian carcinomas demonstrate better NACT outcomes in BRCA2 vs. BRCA1 mutation carriers. The opposite trend is observed in BC, which is likely to be attributed to a high frequency of triple-negative disease in BRCA1- but not BRCA2-associated BCs. Triple-negative receptor status rather than BRCA1/2 status is the strongest predictor of response to NACT in BC.
Aim:
BRCA1/2-associated breast and ovarian carcinomas are often regarded as a single entity, assuming that BRCA1 and BRCA2 genes are almost equivalent with regard to their clinical significance. However, BRCA1 and BRCA2 genes differ in their function; therefore, a comparison of treatment outcomes in BRCA1 vs. BRCA2 carriers is warranted.
Methods:
This study focused on consecutive patients treated with neoadjuvant chemotherapy (NACT), given that these subjects are treatment-naive and accessible for immediate assessment of pathological and clinical outcomes.
Results:
BRCA2-associated high-grade serous ovarian carcinomas (HGSOCs) demonstrated significantly higher rates of pathologic complete response (pCR) as compared to BRCA1-related cancers [8/15 (53%) vs. 7/48 (15%), P = 0.004]. In contrast, HER2-negative breast cancer (BC) patients showed a numerically higher rate of pCR in BRCA1 vs. BRCA2 mutation carriers [38/69 (55%) vs. 13/36 (36%), P = 0.1]. However, the comparison with BRCA-wild-type (WT) tumors revealed that this tendency was mainly attributed to the increased prevalence of hormone receptor (HR)-negative disease in the former group. When BC patients were stratified according to the tumor receptor status, the response rates in triple-negative patients were consistently higher than in HR+/HER2– patients across all analyzed subgroups [BRCA1: 35/59 (59%) vs. 3/10 (30%); BRCA2: 5/10 (50%) vs. 8/26 (31%); WT: 31/76 (41%) vs. 12/74 (16%); Mantel-Haenzsel P < 0.001]. Logistic regression analysis revealed that the odds ratio (OR) for achieving pCR was higher for receptor status (triple-negative vs. HR+: OR = 3.4, 95% CI 1.9–6.0, P < 0.001) than for BRCA status (any mutation vs. WT: OR = 2.1, 95% CI 1.2–3.6, P = 0.008). The addition of carboplatin did not improve pCR rates in BRCA1- or BRCA2-associated BCs, while there was a numerically higher efficacy of carboplatin-containing regimens in patients with WT triple-negative tumors [14/26 (54%) vs. 15/44 (34%), P = 0.13].
Conclusions:
Hereditary ovarian carcinomas demonstrate better NACT outcomes in BRCA2 vs. BRCA1 mutation carriers. The opposite trend is observed in BC, which is likely to be attributed to a high frequency of triple-negative disease in BRCA1- but not BRCA2-associated BCs. Triple-negative receptor status rather than BRCA1/2 status is the strongest predictor of response to NACT in BC.
DOI: https://doi.org/10.37349/etat.2025.1002325
Pancreatic ductal adenocarcinoma (PDAC) is among the top causes of cancer-induced mortality, frequently diagnosed too late to be treated effectively, due to the poor prognosis and the limited successful therapeutic options. Apart from the conventional treatments, new multimodal therapies have emerged utilizing different scientific fields for the improvement of the survival and quality of patients’ lives. The advancement of nanotechnology leads the way to more personalized medicine and the use of targeted theranostics carriers for deep-seated cancers such as PDAC. New nanotechnology innovations such as specialized photo-sensitizing drug nanocarriers, can effectively improve photodynamic therapy (PDT) of PDAC and enhance phototherapy’s action through surface plasmon resonance phenomenon, as another recently re-emerged non- or minimally invasive possible treatment of such diseases. Despite the scientific advancements, significant hurdles remain and many parameters need to be examined. However, the novel application of nano-biophotonic techniques and the convergence of different science fields offer promise for the treatment of difficult-to-treat diseases, like PDAC.
Pancreatic ductal adenocarcinoma (PDAC) is among the top causes of cancer-induced mortality, frequently diagnosed too late to be treated effectively, due to the poor prognosis and the limited successful therapeutic options. Apart from the conventional treatments, new multimodal therapies have emerged utilizing different scientific fields for the improvement of the survival and quality of patients’ lives. The advancement of nanotechnology leads the way to more personalized medicine and the use of targeted theranostics carriers for deep-seated cancers such as PDAC. New nanotechnology innovations such as specialized photo-sensitizing drug nanocarriers, can effectively improve photodynamic therapy (PDT) of PDAC and enhance phototherapy’s action through surface plasmon resonance phenomenon, as another recently re-emerged non- or minimally invasive possible treatment of such diseases. Despite the scientific advancements, significant hurdles remain and many parameters need to be examined. However, the novel application of nano-biophotonic techniques and the convergence of different science fields offer promise for the treatment of difficult-to-treat diseases, like PDAC.
DOI: https://doi.org/10.37349/etat.2025.1002326
This article belongs to the special issue Use of Different Radiation Treatment Modalities in Cancer Therapy: The Role of Inflammation and Immune Response
Osteosarcoma is the most prevalent primary malignant bone tumor affecting adolescents and young adults. Despite advancements in cancer therapies, its prognosis remains poor due to its aggressive nature and early propensity for metastasis—often present at the time of diagnosis. The etiology of osteosarcoma is multifactorial, involving genetic predispositions, environmental exposures, and familial syndromes. While treatment strategies are largely dictated by tumor stage, neoadjuvant chemotherapy followed by surgical resection remains the cornerstone of management. This review provides a comprehensive overview of osteosarcoma, including its historical context, subclassifications, clinical presentation, diagnostic approaches, and evolving treatment modalities. Recent therapeutic innovations—such as gene therapy, immunotherapy, radiation advances, and tyrosine kinase inhibitors—are discussed in detail, highlighting their mechanisms and clinical potential. By synthesizing current literature and identifying ongoing challenges, this review aims to inform clinicians and researchers of recent progress while highlighting critical gaps to guide future research and improve patient outcomes in osteosarcoma care.
Osteosarcoma is the most prevalent primary malignant bone tumor affecting adolescents and young adults. Despite advancements in cancer therapies, its prognosis remains poor due to its aggressive nature and early propensity for metastasis—often present at the time of diagnosis. The etiology of osteosarcoma is multifactorial, involving genetic predispositions, environmental exposures, and familial syndromes. While treatment strategies are largely dictated by tumor stage, neoadjuvant chemotherapy followed by surgical resection remains the cornerstone of management. This review provides a comprehensive overview of osteosarcoma, including its historical context, subclassifications, clinical presentation, diagnostic approaches, and evolving treatment modalities. Recent therapeutic innovations—such as gene therapy, immunotherapy, radiation advances, and tyrosine kinase inhibitors—are discussed in detail, highlighting their mechanisms and clinical potential. By synthesizing current literature and identifying ongoing challenges, this review aims to inform clinicians and researchers of recent progress while highlighting critical gaps to guide future research and improve patient outcomes in osteosarcoma care.
DOI: https://doi.org/10.37349/etat.2025.1002324
Aim:
Penile cancer (PeCa) is a rare malignancy strongly associated with poor genital hygiene and is more prevalent in regions with low socioeconomic status. PeCa accounts for approximately 2% to 4% of all male cancers in Brazil, with higher incidence in the North and Northeast regions. Despite its aggressive nature, the molecular mechanisms underlying PeCa remain poorly understood. We performed whole-exome sequencing in a Brazilian cohort of patients with PeCa to identify potentially pathogenic genetic alterations associated with tumor development and progression.
Methods:
Tumor tissue samples were obtained from patients diagnosed with PeCa. DNA was extracted and subjected to whole-exome sequencing. Human papillomavirus (HPV) genotyping was performed for subtypes 16 and 18. Control samples were collected from individuals without PeCa or other genital diseases.
Results:
The cohort demonstrated considerable genetic heterogeneity. Multiple gene mutations were identified in tumor samples, many of which are involved in carcinogenesis-related biological pathways. Distinct molecular profiles were observed, suggesting diverse tumorigenic mechanisms. MUC16 (present in 11/12 patients, 91.7%) and PABPC1 (8/12 patients, 66.7%) were the most frequently mutated genes. HPV-16 was detected in a subset of cases; however, no consistent association with more aggressive disease was identified.
Conclusions:
This study provides new insights into the genomic landscape of PeCa in a Brazilian population. The findings highlight the presence of heterogeneous and potentially pathogenic mutations, reinforcing the need for further molecular characterization and exploration of novel therapeutic targets in PeCa.
Aim:
Penile cancer (PeCa) is a rare malignancy strongly associated with poor genital hygiene and is more prevalent in regions with low socioeconomic status. PeCa accounts for approximately 2% to 4% of all male cancers in Brazil, with higher incidence in the North and Northeast regions. Despite its aggressive nature, the molecular mechanisms underlying PeCa remain poorly understood. We performed whole-exome sequencing in a Brazilian cohort of patients with PeCa to identify potentially pathogenic genetic alterations associated with tumor development and progression.
Methods:
Tumor tissue samples were obtained from patients diagnosed with PeCa. DNA was extracted and subjected to whole-exome sequencing. Human papillomavirus (HPV) genotyping was performed for subtypes 16 and 18. Control samples were collected from individuals without PeCa or other genital diseases.
Results:
The cohort demonstrated considerable genetic heterogeneity. Multiple gene mutations were identified in tumor samples, many of which are involved in carcinogenesis-related biological pathways. Distinct molecular profiles were observed, suggesting diverse tumorigenic mechanisms. MUC16 (present in 11/12 patients, 91.7%) and PABPC1 (8/12 patients, 66.7%) were the most frequently mutated genes. HPV-16 was detected in a subset of cases; however, no consistent association with more aggressive disease was identified.
Conclusions:
This study provides new insights into the genomic landscape of PeCa in a Brazilian population. The findings highlight the presence of heterogeneous and potentially pathogenic mutations, reinforcing the need for further molecular characterization and exploration of novel therapeutic targets in PeCa.
DOI: https://doi.org/10.37349/etat.2025.1002323
This article belongs to the special issue Predictive and Prognostic Biomarkers in Cancer: Towards the Precision Medicine Era
Transforming growth factor-β (TGF-β) is a multifunctional molecule with a dual role in carcinogenesis. Recent studies have demonstrated its various effects on cancer-related processes. However, the identification of TGF-β and TGF-β signaling pathway regulators in extracellular vesicles (EVs) appears promising for targeting them to control cancer progression associated with drug resistance. Exosomal TGF-β has been shown to be implicated in cancer cell phenotypic plasticity, a dynamic feature of cancer cells, and an evasive process hampering treatment efficacy. Additionally, EVs can influence the metastatic cascade through mechanisms, including their effects on the immune system and their binding to extracellular matrix (ECM) proteins. These processes collaborate to provide a supportive microenvironment for the development and growth of metastatic tumors. A deeper understanding of the mechanisms by which EVs facilitate TGF-β-mediated intercellular communication may have practical implications for better controlling oncological disorders and providing new methods for cancer diagnostics and treatment, including approaches targeting EVs.
Transforming growth factor-β (TGF-β) is a multifunctional molecule with a dual role in carcinogenesis. Recent studies have demonstrated its various effects on cancer-related processes. However, the identification of TGF-β and TGF-β signaling pathway regulators in extracellular vesicles (EVs) appears promising for targeting them to control cancer progression associated with drug resistance. Exosomal TGF-β has been shown to be implicated in cancer cell phenotypic plasticity, a dynamic feature of cancer cells, and an evasive process hampering treatment efficacy. Additionally, EVs can influence the metastatic cascade through mechanisms, including their effects on the immune system and their binding to extracellular matrix (ECM) proteins. These processes collaborate to provide a supportive microenvironment for the development and growth of metastatic tumors. A deeper understanding of the mechanisms by which EVs facilitate TGF-β-mediated intercellular communication may have practical implications for better controlling oncological disorders and providing new methods for cancer diagnostics and treatment, including approaches targeting EVs.
DOI: https://doi.org/10.37349/etat.2025.1002322
Circulating tumor cells (CTCs) are cancer cells that are detached from the primary and metastatic tumor site and invade the bloodstream. Most importantly, CTCs are the key players in the development of metastasis. As one of the main components of liquid biopsy, they may significantly contribute to improvements in early cancer diagnosis, monitoring response to therapy, and predicting recurrence of the disease. Although identifying and analyzing CTCs offers the potential for a real-time liquid biopsy, their detection is associated with a number of challenges, which mainly stem from three sources: complexity of the CTCs, complexity of the media (blood), and performance of the detection assays. Particularly, low concentration of the CTCs and the presence of a vast population of hematopoietic cells in the blood make their detection technically complex. The heterogeneity of the target cells and not enough sensitivity of the measuring platforms are also among major technical challenges in CTC detection. Therefore, this review aims to give an update on various methods developed for CTC isolation, including chip-based assays and biosensors. The work will elucidate various challenges associated with the isolation and detection of CTCs and showcase the studies that aimed to tackle them. A number of available commercial platforms for CTC detection and hurdles associated with their widespread applications in clinical settings will also be discussed.
Circulating tumor cells (CTCs) are cancer cells that are detached from the primary and metastatic tumor site and invade the bloodstream. Most importantly, CTCs are the key players in the development of metastasis. As one of the main components of liquid biopsy, they may significantly contribute to improvements in early cancer diagnosis, monitoring response to therapy, and predicting recurrence of the disease. Although identifying and analyzing CTCs offers the potential for a real-time liquid biopsy, their detection is associated with a number of challenges, which mainly stem from three sources: complexity of the CTCs, complexity of the media (blood), and performance of the detection assays. Particularly, low concentration of the CTCs and the presence of a vast population of hematopoietic cells in the blood make their detection technically complex. The heterogeneity of the target cells and not enough sensitivity of the measuring platforms are also among major technical challenges in CTC detection. Therefore, this review aims to give an update on various methods developed for CTC isolation, including chip-based assays and biosensors. The work will elucidate various challenges associated with the isolation and detection of CTCs and showcase the studies that aimed to tackle them. A number of available commercial platforms for CTC detection and hurdles associated with their widespread applications in clinical settings will also be discussed.
DOI: https://doi.org/10.37349/etat.2025.1002321
This article belongs to the special issue Liquid Biopsy: Has Already Changed the Clinical Decision-Making in Solid Tumors Treatment?
Aim:
Circular RNA (circRNA) is a class of noncoding, single-stranded RNA generated by backsplicing, a process where the 5’ and 3’ ends of an RNA are covalently joined. Virally encoded circRNAs have been identified in several members of Gammaherpesvirinae, including Kaposi’s sarcoma-associated herpesvirus (KSHV). In KSHV, the viral interferon regulatory factor 4 (vIRF4) region produces two isoforms of circRNA (circ-vIRF4) that are detectable during latency and reactivation. Given the growing literature implicating circRNA in human diseases, a role may exist for circ-vIRF4 in the development of KSHV malignancies. Therefore, the aim of this study is to characterize the function of vIRF4 circRNAs.
Methods:
A KSHV mutant (Δcirc-vIRF4) was generated in the BAC16 bacmid and transfected into 293T and iSLK cells. Expression of circRNA after mutagenesis was assessed by qualitative and quantitative PCR. Host and viral gene expression in iSLK cells during both viral latency and reactivation were also assessed by RNA-seq.
Results:
RT-PCR of Δcirc-vIRF4-infected iSLK cells demonstrated no expression of wild-type (WT) isoforms, but PCR cloning showed that alternative backsplice sites were used to express novel vIRF4 circRNAs, where the most prominent isoform was a 1,020 nt isoform. RNA-seq analyses comparing WT- and Δcirc-vIRF4-infected iSLK cells demonstrated significant differential expression of both host and viral genes during both phases of the viral life cycle. Gene ontology analyses returned terms related to cell adhesion, proliferation, and migration for both datasets, as well as kinase signaling and apoptosis for the lytic dataset.
Conclusions:
These results show that KSHV can switch to an alternative backsplice site for vIRF4 circRNA production in the absence of a canonical splice site and that circ-vIRF4 contributes to the regulation of both host and viral gene expression through an unknown mechanism.
Aim:
Circular RNA (circRNA) is a class of noncoding, single-stranded RNA generated by backsplicing, a process where the 5’ and 3’ ends of an RNA are covalently joined. Virally encoded circRNAs have been identified in several members of Gammaherpesvirinae, including Kaposi’s sarcoma-associated herpesvirus (KSHV). In KSHV, the viral interferon regulatory factor 4 (vIRF4) region produces two isoforms of circRNA (circ-vIRF4) that are detectable during latency and reactivation. Given the growing literature implicating circRNA in human diseases, a role may exist for circ-vIRF4 in the development of KSHV malignancies. Therefore, the aim of this study is to characterize the function of vIRF4 circRNAs.
Methods:
A KSHV mutant (Δcirc-vIRF4) was generated in the BAC16 bacmid and transfected into 293T and iSLK cells. Expression of circRNA after mutagenesis was assessed by qualitative and quantitative PCR. Host and viral gene expression in iSLK cells during both viral latency and reactivation were also assessed by RNA-seq.
Results:
RT-PCR of Δcirc-vIRF4-infected iSLK cells demonstrated no expression of wild-type (WT) isoforms, but PCR cloning showed that alternative backsplice sites were used to express novel vIRF4 circRNAs, where the most prominent isoform was a 1,020 nt isoform. RNA-seq analyses comparing WT- and Δcirc-vIRF4-infected iSLK cells demonstrated significant differential expression of both host and viral genes during both phases of the viral life cycle. Gene ontology analyses returned terms related to cell adhesion, proliferation, and migration for both datasets, as well as kinase signaling and apoptosis for the lytic dataset.
Conclusions:
These results show that KSHV can switch to an alternative backsplice site for vIRF4 circRNA production in the absence of a canonical splice site and that circ-vIRF4 contributes to the regulation of both host and viral gene expression through an unknown mechanism.
DOI: https://doi.org/10.37349/etat.2025.1002320
This article belongs to the special issue Potential of Non-Coding RNAs in Cancer Research and Treatment
Musculoskeletal sarcomas represent heterogeneous and rare malignant bone and soft tissue tumors, affecting children and adults. Patients exhibiting poor clinical outcomes are often described, being associated with non-response to chemotherapy, amputation needs, or metastatic disease. Potential biomarkers contributing to diagnosis, prognosis, and treatment response could improve this scenario. Despite this, little is known about the genomic aspects of musculoskeletal sarcomas. DNA methylation is the most studied epigenetic mechanism, where changes in methylation profiling are characteristic hallmarks of cancer. Cancer-related methylome profiling has been investigated both in tumor biopsies (genomic DNA) and liquid biopsies (cell-free DNA). Epigenetic therapies by using DNA-demethylating drugs are promising strategies for cancer treatment. This review will discuss translational studies describing how DNA methylation landscape of musculoskeletal sarcomas can be a powerful molecular tool to improve diagnostic accuracy, predict prognosis, and treatment response. Additionally, this review will describe the promising role of epigenetics-targeted drugs as well as the ongoing clinical trials for sarcomas, highlighting the challenges and future directions.
Musculoskeletal sarcomas represent heterogeneous and rare malignant bone and soft tissue tumors, affecting children and adults. Patients exhibiting poor clinical outcomes are often described, being associated with non-response to chemotherapy, amputation needs, or metastatic disease. Potential biomarkers contributing to diagnosis, prognosis, and treatment response could improve this scenario. Despite this, little is known about the genomic aspects of musculoskeletal sarcomas. DNA methylation is the most studied epigenetic mechanism, where changes in methylation profiling are characteristic hallmarks of cancer. Cancer-related methylome profiling has been investigated both in tumor biopsies (genomic DNA) and liquid biopsies (cell-free DNA). Epigenetic therapies by using DNA-demethylating drugs are promising strategies for cancer treatment. This review will discuss translational studies describing how DNA methylation landscape of musculoskeletal sarcomas can be a powerful molecular tool to improve diagnostic accuracy, predict prognosis, and treatment response. Additionally, this review will describe the promising role of epigenetics-targeted drugs as well as the ongoing clinical trials for sarcomas, highlighting the challenges and future directions.
DOI: https://doi.org/10.37349/etat.2025.1002319
Aim:
This research aims to guide future strategies for personalized treatment of primary mediastinal large B-cell lymphoma (PMBCL), particularly to identify high-risk patients who may benefit from incorporating immune checkpoint inhibitors (ICIs) in the first-line setting.
Methods:
A retrospective, single-center study included 254 newly diagnosed PMBCL patients treated with rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (R-DA-EPOCH), rituximab, modified protocol NHL-BFM-90 (RmNHL-BFM-90), or R-DA-EPOCH combined with nivolumab. Clinical parameters, immunohistochemical markers [programmed death ligand-1 (PD-L1), programmed death-1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), human leucocyte antigen (HLA)-DR, Ki-67, multiple myeloma oncogene 1 (MUM1)], molecular markers (mutations in tumor protein p53 (TP53), CD58, beta-2-microglobulin (B2M), and exportin 1 (XPO1) genes; short tandem repeats at 6p21.3 [major histocompatibility complex (MHC) class I/II], 9p24.1 (PD-L1/PD-L2), 16p13.13 [class II, MHC, transactivator gene (CIITA)]), and cytogenetic profiles [myelocytomatosis oncogene (MYC)/8q24, B-cell lymphoma 2 (BCL2)/18q21, BCL6/3q27, del17p13, and karyotype abnormalities] were analyzed.
Results:
The addition of nivolumab to R-DA-EPOCH as a first-line regimen significantly improved event-free survival (EFS; P = 0.018). This study identified that adverse prognostic factors for PMBCL include allelic imbalance at specific loci 6p21.3 (MHC class I/II), 9p24.1 (PD-L1/PD-L2), and 16p13.13 (CIITA). Incorporating nivolumab into the R-DA-EPOCH regimen as a first-line therapy has shown potential in reducing adverse prognostic factors.
Conclusions:
These findings suggest that high-risk patients may benefit significantly from the early incorporation of ICIs into their treatment plans.
Aim:
This research aims to guide future strategies for personalized treatment of primary mediastinal large B-cell lymphoma (PMBCL), particularly to identify high-risk patients who may benefit from incorporating immune checkpoint inhibitors (ICIs) in the first-line setting.
Methods:
A retrospective, single-center study included 254 newly diagnosed PMBCL patients treated with rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (R-DA-EPOCH), rituximab, modified protocol NHL-BFM-90 (RmNHL-BFM-90), or R-DA-EPOCH combined with nivolumab. Clinical parameters, immunohistochemical markers [programmed death ligand-1 (PD-L1), programmed death-1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), human leucocyte antigen (HLA)-DR, Ki-67, multiple myeloma oncogene 1 (MUM1)], molecular markers (mutations in tumor protein p53 (TP53), CD58, beta-2-microglobulin (B2M), and exportin 1 (XPO1) genes; short tandem repeats at 6p21.3 [major histocompatibility complex (MHC) class I/II], 9p24.1 (PD-L1/PD-L2), 16p13.13 [class II, MHC, transactivator gene (CIITA)]), and cytogenetic profiles [myelocytomatosis oncogene (MYC)/8q24, B-cell lymphoma 2 (BCL2)/18q21, BCL6/3q27, del17p13, and karyotype abnormalities] were analyzed.
Results:
The addition of nivolumab to R-DA-EPOCH as a first-line regimen significantly improved event-free survival (EFS; P = 0.018). This study identified that adverse prognostic factors for PMBCL include allelic imbalance at specific loci 6p21.3 (MHC class I/II), 9p24.1 (PD-L1/PD-L2), and 16p13.13 (CIITA). Incorporating nivolumab into the R-DA-EPOCH regimen as a first-line therapy has shown potential in reducing adverse prognostic factors.
Conclusions:
These findings suggest that high-risk patients may benefit significantly from the early incorporation of ICIs into their treatment plans.
DOI: https://doi.org/10.37349/etat.2025.1002318
This article belongs to the special issue Immune Checkpoint Therapy and Biomarkers in Cancer
The role of circulating tumor DNA (ctDNA) in urothelial cancers is a rapidly evolving area of research. Urothelial cancer is the most common subtype of bladder cancer, and biomarkers that predict response or prognosticate outcomes have been long sought after. Tumor-informed ctDNA assays have been utilized in several other cancers and increasingly used in both muscle invasive bladder cancer (MIBC) and metastatic urothelial cancer (mUC) to inform treatment decision-making. While a universal consensus on ctDNA testing has not been fully defined and discussed herein, understanding its benefits and limitations is important to help guide the practical application in the clinic.
The role of circulating tumor DNA (ctDNA) in urothelial cancers is a rapidly evolving area of research. Urothelial cancer is the most common subtype of bladder cancer, and biomarkers that predict response or prognosticate outcomes have been long sought after. Tumor-informed ctDNA assays have been utilized in several other cancers and increasingly used in both muscle invasive bladder cancer (MIBC) and metastatic urothelial cancer (mUC) to inform treatment decision-making. While a universal consensus on ctDNA testing has not been fully defined and discussed herein, understanding its benefits and limitations is important to help guide the practical application in the clinic.
DOI: https://doi.org/10.37349/etat.2025.1002317
This article belongs to the special issue Liquid Biopsy: Has Already Changed the Clinical Decision-Making in Solid Tumors Treatment?
Background:
Different tumor markers are utilized in the assessment of breast cancer. The function of these markers in assessing, tracking, and following up on breast cancer has drawn the interest of numerous researchers. Nonetheless, contradictory findings from research continue to raise questions regarding their effectiveness. Consequently, this research was carried out to evaluate the efficacy of carbohydrate antigen-125 (CA-125) in the treatment of breast cancer.
Methods:
A thorough investigation was performed in the PubMed, Scopus, and Web of Science databases utilizing relevant keywords: CA-125, breast cancer, screening and diagnosis, and Mesh to locate articles published before August 2023 without any time limitations. The analysis included observational studies in English pertinent to the study’s objective, while review articles, case reports, editor letters, comments, and other reports were not considered. Articles were sought, examined, included, and evaluated according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The EndNote X9 program has been utilized for item management. The review included articles that investigated the predictive function of CA-125 in the screening, diagnosis, and anticipation for the early and proper detection of breast cancer.
Results:
In the initial search, 1,475 articles were obtained. After screening and eligibility assessment, 33 studies were reviewed. Based on the findings of the studies, CA-125 can play a role in the diagnosis of breast cancer, its type and stage, early detection of recurrence and metastasis, treatment efficiency, prognosis, and survival rate.
Discussion:
The role of CA-125 as a biomarker for early detection, staging, and monitoring of recurrence and metastasis in breast cancer is still uncertain and needs additional research.
Background:
Different tumor markers are utilized in the assessment of breast cancer. The function of these markers in assessing, tracking, and following up on breast cancer has drawn the interest of numerous researchers. Nonetheless, contradictory findings from research continue to raise questions regarding their effectiveness. Consequently, this research was carried out to evaluate the efficacy of carbohydrate antigen-125 (CA-125) in the treatment of breast cancer.
Methods:
A thorough investigation was performed in the PubMed, Scopus, and Web of Science databases utilizing relevant keywords: CA-125, breast cancer, screening and diagnosis, and Mesh to locate articles published before August 2023 without any time limitations. The analysis included observational studies in English pertinent to the study’s objective, while review articles, case reports, editor letters, comments, and other reports were not considered. Articles were sought, examined, included, and evaluated according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The EndNote X9 program has been utilized for item management. The review included articles that investigated the predictive function of CA-125 in the screening, diagnosis, and anticipation for the early and proper detection of breast cancer.
Results:
In the initial search, 1,475 articles were obtained. After screening and eligibility assessment, 33 studies were reviewed. Based on the findings of the studies, CA-125 can play a role in the diagnosis of breast cancer, its type and stage, early detection of recurrence and metastasis, treatment efficiency, prognosis, and survival rate.
Discussion:
The role of CA-125 as a biomarker for early detection, staging, and monitoring of recurrence and metastasis in breast cancer is still uncertain and needs additional research.
DOI: https://doi.org/10.37349/etat.2025.1002316
With the escalating application of immune checkpoint inhibitors (ICIs) in solid tumors, these therapies have demonstrated clinical benefits but remain hampered by relatively low response rates. Reliable biomarkers to predict ICIs responsiveness are essential for selecting appropriate patients and optimizing therapeutic outcomes. Given the pivotal role of tumor-draining lymph nodes (TDLNs) in orchestrating systemic antitumor immunity, their intrinsic features—such as dynamic organization in T cell subsets and functional status of antigen-presenting cells, hold considerable potential as predictive biomarkers for ICIs. Moreover, the complexity of ICIs-induced responses in TDLNs necessitates integrating multiple biomarkers for accurate prediction. Through continuous refinement of predictive strategies, TDLNs are poised to play an indispensable role in enhancing ICIs efficacy and guiding personalized immunotherapy. Here, we provide a review to discuss the possibility of using the intrinsic features of TDLNs as a predictive marker for ICI therapy.
With the escalating application of immune checkpoint inhibitors (ICIs) in solid tumors, these therapies have demonstrated clinical benefits but remain hampered by relatively low response rates. Reliable biomarkers to predict ICIs responsiveness are essential for selecting appropriate patients and optimizing therapeutic outcomes. Given the pivotal role of tumor-draining lymph nodes (TDLNs) in orchestrating systemic antitumor immunity, their intrinsic features—such as dynamic organization in T cell subsets and functional status of antigen-presenting cells, hold considerable potential as predictive biomarkers for ICIs. Moreover, the complexity of ICIs-induced responses in TDLNs necessitates integrating multiple biomarkers for accurate prediction. Through continuous refinement of predictive strategies, TDLNs are poised to play an indispensable role in enhancing ICIs efficacy and guiding personalized immunotherapy. Here, we provide a review to discuss the possibility of using the intrinsic features of TDLNs as a predictive marker for ICI therapy.
DOI: https://doi.org/10.37349/etat.2025.1002315
This article belongs to the special issue Novel Biomarkers in the Immunotherapy Era
Despite major improvements in cancer treatment, detection, and health promotion, the mortality rates of late-stage cancer remain high. This is a critical issue because a large proportion of cancer mortality is experienced by patients who have late-stage disease at diagnosis. As survival is substantially higher for almost all cancers when diagnosed at an early stage, effective early cancer detection strategies could drastically reduce overall cancer mortality. Advances in various technologies have culminated in the development of liquid biopsies. The tumour biomarkers applied for non- or minimally-invasive cancer detection include tumour cells and their components in bodily fluids, especially peripheral blood for circulating tumour biomarkers. The most well-studied circulating tumour biomarkers in recent years for the early detection of cancer are circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA), with research into other classes rapidly expanding. CTCs and ctDNA have been detected at an early stage in several types of cancer with high specificity, aiding risk stratification and, in some cases, identifying clinically actionable molecular features. Therefore, these circulating biomarkers offer several advantages over the traditional cancer detection methods. Although their limitations are considerable, the evolving evidence suggests they have tremendous potential as tools for early cancer detection. In this review, we evaluate the development and applications of circulating biomarkers for early cancer detection, with a focus on CTCs and ctDNA. We also briefly explore the emerging evidence on extracellular vesicles, circulating proteins and synthetic biomarkers, discuss the limitations of current approaches and provide suggestions to achieve further progress in this setting.
Despite major improvements in cancer treatment, detection, and health promotion, the mortality rates of late-stage cancer remain high. This is a critical issue because a large proportion of cancer mortality is experienced by patients who have late-stage disease at diagnosis. As survival is substantially higher for almost all cancers when diagnosed at an early stage, effective early cancer detection strategies could drastically reduce overall cancer mortality. Advances in various technologies have culminated in the development of liquid biopsies. The tumour biomarkers applied for non- or minimally-invasive cancer detection include tumour cells and their components in bodily fluids, especially peripheral blood for circulating tumour biomarkers. The most well-studied circulating tumour biomarkers in recent years for the early detection of cancer are circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA), with research into other classes rapidly expanding. CTCs and ctDNA have been detected at an early stage in several types of cancer with high specificity, aiding risk stratification and, in some cases, identifying clinically actionable molecular features. Therefore, these circulating biomarkers offer several advantages over the traditional cancer detection methods. Although their limitations are considerable, the evolving evidence suggests they have tremendous potential as tools for early cancer detection. In this review, we evaluate the development and applications of circulating biomarkers for early cancer detection, with a focus on CTCs and ctDNA. We also briefly explore the emerging evidence on extracellular vesicles, circulating proteins and synthetic biomarkers, discuss the limitations of current approaches and provide suggestions to achieve further progress in this setting.
DOI: https://doi.org/10.37349/etat.2025.1002314
