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A functional immune system is a key antagonist of cancer cell growth. Cytokines such as interferons (IFNs) promote the onset of inflammation, turn cells into an anti-viral state, and shape the dynamic tumor-immune cell interactome. Recent work illustrates how type I IFNs contribute to the resolution of inflammatory conditions. This involves macrophage-mediated efferocytosis for the clearance of apoptotic cells and the intrinsic capacity of type I IFNs to restrict their own autocrine signaling loops via the IFN-stimulated gene 15 (ISG15) protein. We discuss how this may affect tumor cells and how acetylation-dependent processes can affect the phosphorylation-dependent signaling cascades that augment IFN-dependent gene expression.
A functional immune system is a key antagonist of cancer cell growth. Cytokines such as interferons (IFNs) promote the onset of inflammation, turn cells into an anti-viral state, and shape the dynamic tumor-immune cell interactome. Recent work illustrates how type I IFNs contribute to the resolution of inflammatory conditions. This involves macrophage-mediated efferocytosis for the clearance of apoptotic cells and the intrinsic capacity of type I IFNs to restrict their own autocrine signaling loops via the IFN-stimulated gene 15 (ISG15) protein. We discuss how this may affect tumor cells and how acetylation-dependent processes can affect the phosphorylation-dependent signaling cascades that augment IFN-dependent gene expression.
DOI: https://doi.org/10.37349/etat.2026.1002399
Cannabis sativa has a long history in ethnomedicine, but advances in molecular biology and regulatory shifts have reignited global interest in its therapeutic potential. Cannabinoid research in the 21st century spans molecular pharmacology, clinical applications, and public health integration. This study provides a comprehensive synthesis of the current state of knowledge. This narrative review synthesizes evidence from Scopus, PubMed, and Google Scholar using Medical Subject Headings-based search strategies. Only articles published in English were included, without restrictions on publication year; however, greater emphasis was placed on recent studies to ensure currency, while seminal and historically important publications were included where necessary to provide foundational context. Relevant studies were thematically analyzed and summarized under predefined headings. Major phytocannabinoids have been identified, with Δ9-tetrahydrocannabinol, cannabidiol, and cannabigerol as key therapeutic candidates. Preclinical studies have shown neuroprotective, anti-inflammatory, analgesic, immunomodulatory, and anticancer effects, but clinical translation remains limited by variability, dosing challenges, and inconsistent reproducibility. These effects are mediated through the endocannabinoid system and related receptor networks. Emerging evidence suggests that epigenetic regulation and precision medicine approaches may enhance individualized cannabinoid therapy. However, safety concerns, including cognitive and psychiatric effects, drug interactions, and dependence, require robust pharmacovigilance. Fragmented regulatory frameworks continue to hinder research and equitable access, underscoring the need for standardized formulations, clinician training, and equity-focused integration into health systems. Cannabinoid therapeutics represent a rapidly evolving field with promise in multiple medical domains. Future progress hinges on harmonizing regulations, expanding clinical evidence, and integrating precision medicine, equity, and public health principles to maximize therapeutic benefits while minimizing risks.
Cannabis sativa has a long history in ethnomedicine, but advances in molecular biology and regulatory shifts have reignited global interest in its therapeutic potential. Cannabinoid research in the 21st century spans molecular pharmacology, clinical applications, and public health integration. This study provides a comprehensive synthesis of the current state of knowledge. This narrative review synthesizes evidence from Scopus, PubMed, and Google Scholar using Medical Subject Headings-based search strategies. Only articles published in English were included, without restrictions on publication year; however, greater emphasis was placed on recent studies to ensure currency, while seminal and historically important publications were included where necessary to provide foundational context. Relevant studies were thematically analyzed and summarized under predefined headings. Major phytocannabinoids have been identified, with Δ9-tetrahydrocannabinol, cannabidiol, and cannabigerol as key therapeutic candidates. Preclinical studies have shown neuroprotective, anti-inflammatory, analgesic, immunomodulatory, and anticancer effects, but clinical translation remains limited by variability, dosing challenges, and inconsistent reproducibility. These effects are mediated through the endocannabinoid system and related receptor networks. Emerging evidence suggests that epigenetic regulation and precision medicine approaches may enhance individualized cannabinoid therapy. However, safety concerns, including cognitive and psychiatric effects, drug interactions, and dependence, require robust pharmacovigilance. Fragmented regulatory frameworks continue to hinder research and equitable access, underscoring the need for standardized formulations, clinician training, and equity-focused integration into health systems. Cannabinoid therapeutics represent a rapidly evolving field with promise in multiple medical domains. Future progress hinges on harmonizing regulations, expanding clinical evidence, and integrating precision medicine, equity, and public health principles to maximize therapeutic benefits while minimizing risks.
DOI: https://doi.org/10.37349/eds.2026.1008177
Gastric cancer is one of the most prevalent malignancies of the gastrointestinal tract. Worldwide, it ranks as the fourth most commonly diagnosed cancer and the third leading cause of cancer-related mortality. A variety of diagnostic approaches are used for the detection of gastric cancer. Early diagnosis of gastric cancer is crucial, as timely treatment can significantly improve patient prognosis. Detection and monitoring of circulating tumor DNA (ctDNA) provide valuable clinical information while minimizing the need for invasive procedures, such as tissue biopsy. These ctDNAs have been identified as reliable and accurate biomarkers for gastric cancer. The application of ctDNA in gastric cancer plays a significant role in the early diagnosis, detection, and monitoring of minimal residual disease, as well as in the clinical management of advanced-stage disease.
Gastric cancer is one of the most prevalent malignancies of the gastrointestinal tract. Worldwide, it ranks as the fourth most commonly diagnosed cancer and the third leading cause of cancer-related mortality. A variety of diagnostic approaches are used for the detection of gastric cancer. Early diagnosis of gastric cancer is crucial, as timely treatment can significantly improve patient prognosis. Detection and monitoring of circulating tumor DNA (ctDNA) provide valuable clinical information while minimizing the need for invasive procedures, such as tissue biopsy. These ctDNAs have been identified as reliable and accurate biomarkers for gastric cancer. The application of ctDNA in gastric cancer plays a significant role in the early diagnosis, detection, and monitoring of minimal residual disease, as well as in the clinical management of advanced-stage disease.
DOI: https://doi.org/10.37349/edd.2026.1005132
Pomegranate has long been used in Greco-Arab medicine for gastrointestinal, cardiovascular, metabolic, and inflammatory disorders. It has been described to relieve nausea, vomiting, abdominal pain, diarrhoea, palpitations, etc. Modern scientific studies have validated these uses, attributing them to a rich phytochemical profile of polyphenols, flavonoids, anthocyanins, tannins, punicalagins, and ellagitannins. However, the precise mechanism of action and optimal application strategies for pomegranate in systemic diseases remain an area of investigation. Metabolomics provides a robust platform for elucidating the intricate relationships between pomegranate bioactives and human physiology. Therefore, to evaluate the therapeutic potential of pomegranate (Punica granatum L.) and find out how metabolomics can enhance its pharmacological applications, a literature review was conducted using ancient & modern pharmacology books, PubMed, Scopus, Web of Science, and Google Scholar. Human clinical trials were prioritized, followed by in vivo and in vitro studies. Evidence was synthesized qualitatively with emphasis on metabolomic findings. The research question was framed to determine whether metabolomics can enhance and optimize the therapeutic potential of pomegranate. Metabolomic studies demonstrated that pomegranate exhibits all its biological activities through gut microbiota-derived metabolites, particularly urolithins, which play a key role in mediating these effects. Therefore, it was concluded that integration of metabolomics with traditional pharmacology can enhance pomegranate-based therapeutics and support its role in precision nutrition.
Pomegranate has long been used in Greco-Arab medicine for gastrointestinal, cardiovascular, metabolic, and inflammatory disorders. It has been described to relieve nausea, vomiting, abdominal pain, diarrhoea, palpitations, etc. Modern scientific studies have validated these uses, attributing them to a rich phytochemical profile of polyphenols, flavonoids, anthocyanins, tannins, punicalagins, and ellagitannins. However, the precise mechanism of action and optimal application strategies for pomegranate in systemic diseases remain an area of investigation. Metabolomics provides a robust platform for elucidating the intricate relationships between pomegranate bioactives and human physiology. Therefore, to evaluate the therapeutic potential of pomegranate (Punica granatum L.) and find out how metabolomics can enhance its pharmacological applications, a literature review was conducted using ancient & modern pharmacology books, PubMed, Scopus, Web of Science, and Google Scholar. Human clinical trials were prioritized, followed by in vivo and in vitro studies. Evidence was synthesized qualitatively with emphasis on metabolomic findings. The research question was framed to determine whether metabolomics can enhance and optimize the therapeutic potential of pomegranate. Metabolomic studies demonstrated that pomegranate exhibits all its biological activities through gut microbiota-derived metabolites, particularly urolithins, which play a key role in mediating these effects. Therefore, it was concluded that integration of metabolomics with traditional pharmacology can enhance pomegranate-based therapeutics and support its role in precision nutrition.
DOI: https://doi.org/10.37349/eff.2026.1010183
This article belongs to the special issue Food-Derived Bioactive Compounds: From Foodomics to Therapeutic Applications
Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), are T-cell-mediated hypersensitivity reactions. Although their causative agents and acute manifestations are well characterized, limited data exist regarding their long-term sequelae, particularly the subsequent development of autoimmune disease. A comprehensive literature review was conducted using PubMed. Given the limited published evidence regarding autoimmune sequelae following SCARs, the search strategy was intentionally broad and included studies published from the 1980s through 2025. Among SCARs, DRESS demonstrated the strongest association with autoimmune disease, including type 1 diabetes mellitus, thyroiditis, bullous pemphigoid, thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, vitiligo, and systemic lupus erythematosus. Proposed pathogenic mechanisms include viral reactivation and persistent immune dysregulation. SJS/TEN has also been associated with fulminant type 1 diabetes mellitus, autoimmune thyroid disease, systemic lupus erythematosus, Sjögren’s syndrome, and the development of positive antinuclear antibodies. In contrast, evidence linking AGEP to autoimmune disease remains limited and conflicting, although associations with CARD14 mutations and polyarteritis nodosa have been reported. Evidence supporting post-SCAR autoimmunity, particularly following DRESS, is growing but remains largely based on case reports and small observational studies. SCARs, particularly DRESS and to a lesser extent SJS/TEN, may predispose patients to autoimmune disease through persistent immune dysregulation and viral reactivation. In contrast, no clear association has been established between AGEP and autoimmune disease. Clinicians should remain vigilant for potential long-term autoimmune sequelae following SCARs and consider multidisciplinary follow-up when clinically appropriate. Further prospective studies are needed to better characterize the underlying mechanisms, incidence, and optimal long-term surveillance strategies associated with these conditions.
Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), are T-cell-mediated hypersensitivity reactions. Although their causative agents and acute manifestations are well characterized, limited data exist regarding their long-term sequelae, particularly the subsequent development of autoimmune disease. A comprehensive literature review was conducted using PubMed. Given the limited published evidence regarding autoimmune sequelae following SCARs, the search strategy was intentionally broad and included studies published from the 1980s through 2025. Among SCARs, DRESS demonstrated the strongest association with autoimmune disease, including type 1 diabetes mellitus, thyroiditis, bullous pemphigoid, thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, vitiligo, and systemic lupus erythematosus. Proposed pathogenic mechanisms include viral reactivation and persistent immune dysregulation. SJS/TEN has also been associated with fulminant type 1 diabetes mellitus, autoimmune thyroid disease, systemic lupus erythematosus, Sjögren’s syndrome, and the development of positive antinuclear antibodies. In contrast, evidence linking AGEP to autoimmune disease remains limited and conflicting, although associations with CARD14 mutations and polyarteritis nodosa have been reported. Evidence supporting post-SCAR autoimmunity, particularly following DRESS, is growing but remains largely based on case reports and small observational studies. SCARs, particularly DRESS and to a lesser extent SJS/TEN, may predispose patients to autoimmune disease through persistent immune dysregulation and viral reactivation. In contrast, no clear association has been established between AGEP and autoimmune disease. Clinicians should remain vigilant for potential long-term autoimmune sequelae following SCARs and consider multidisciplinary follow-up when clinically appropriate. Further prospective studies are needed to better characterize the underlying mechanisms, incidence, and optimal long-term surveillance strategies associated with these conditions.
DOI: https://doi.org/10.37349/eaa.2026.1009131
Bacterial co-infection in patients with coronavirus disease 2019 (COVID-19) can complicate diagnosis because of overlapping clinicoradiologic findings among pathogens. We report a case of suspected triple co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Legionella pneumophila (L. pneumophila), and Streptococcus pneumoniae (S. pneumoniae) after hot-spring travel in a post-splenectomy patient. A man in his 70s with a history of subtotal esophagectomy and concomitant splenectomy for esophageal cancer was admitted with fever, worsening productive cough, and altered sensorium. He had recently traveled to a hot spring with a group that included his wife, who also developed a fever and was diagnosed with COVID-19. On admission, results of urinary antigen tests for L. pneumophila and S. pneumoniae were positive, a SARS-CoV-2 nucleic acid amplification test was positive, and sputum culture yielded S. pneumoniae. Chest computed tomography revealed multifocal bilateral ground-glass opacities, small bilateral pleural effusions, and relatively well-defined right middle-lobe consolidation with air bronchograms in a peribronchovascular distribution. These microbiological and radiological findings supported a suspected triple co-infection rather than COVID-19 alone. Treatment with remdesivir, ceftriaxone, and levofloxacin was initiated, and the patient’s condition improved, with better oxygenation and decreased inflammatory markers. Remdesivir and ceftriaxone were discontinued after 5 days, whereas levofloxacin was continued for 14 days. Follow-up imaging revealed marked improvement, and the patient was discharged. Public health investigations did not detect Legionella at the hot-spring facility or identify any additional linked cases. This case highlights the importance of prompt pathogen-directed evaluation when COVID-19 pneumonia is accompanied by a relevant exposure history, host risk factors, and atypical imaging findings.
Bacterial co-infection in patients with coronavirus disease 2019 (COVID-19) can complicate diagnosis because of overlapping clinicoradiologic findings among pathogens. We report a case of suspected triple co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Legionella pneumophila (L. pneumophila), and Streptococcus pneumoniae (S. pneumoniae) after hot-spring travel in a post-splenectomy patient. A man in his 70s with a history of subtotal esophagectomy and concomitant splenectomy for esophageal cancer was admitted with fever, worsening productive cough, and altered sensorium. He had recently traveled to a hot spring with a group that included his wife, who also developed a fever and was diagnosed with COVID-19. On admission, results of urinary antigen tests for L. pneumophila and S. pneumoniae were positive, a SARS-CoV-2 nucleic acid amplification test was positive, and sputum culture yielded S. pneumoniae. Chest computed tomography revealed multifocal bilateral ground-glass opacities, small bilateral pleural effusions, and relatively well-defined right middle-lobe consolidation with air bronchograms in a peribronchovascular distribution. These microbiological and radiological findings supported a suspected triple co-infection rather than COVID-19 alone. Treatment with remdesivir, ceftriaxone, and levofloxacin was initiated, and the patient’s condition improved, with better oxygenation and decreased inflammatory markers. Remdesivir and ceftriaxone were discontinued after 5 days, whereas levofloxacin was continued for 14 days. Follow-up imaging revealed marked improvement, and the patient was discharged. Public health investigations did not detect Legionella at the hot-spring facility or identify any additional linked cases. This case highlights the importance of prompt pathogen-directed evaluation when COVID-19 pneumonia is accompanied by a relevant exposure history, host risk factors, and atypical imaging findings.
DOI: https://doi.org/10.37349/emed.2026.1001424
This article belongs to the special issue Legionellosis: From Environmental Exposure to Clinical Disease
The therapeutic landscape for obesity is changing rapidly, driven by the recognition of obesity as a chronic, biologically heterogeneous disease, with clinically relevant organ consequences. In this context, the phase 3 SYNCHRONIZE™-1 trial of survodutide, a once-weekly dual agonist of glucagon receptor and glucagon-like peptide 1 (GLP-1) receptor, is notable not simply because it adds another effective incretin-based therapy, but because it tests a broader metabolic concept. By pairing GLP-1-mediated appetite suppression with glucagon-mediated effects on energy expenditure and hepatic lipid handling, survodutide aims to extend treatment beyond appetite control towards coordinated modulation of adiposity, cardiometabolic risk and steatotic liver disease. In adults with obesity without diabetes, SYNCHRONIZE™-1 showed sustained body-weight reductions of approximately 12–13% over 76 weeks, compared with 5.4% with placebo, and increased the proportion of participants achieving clinically ambitious weight-loss thresholds, including at least 20% weight loss. Improvements in waist circumference, glycemic and lipid measures, together with reductions in visceral and liver fat content (LFC) in imaging analyses, support the possibility of benefits that are metabolically broader than scale weight alone. Yet the trial also illustrates familiar tensions in obesity pharmacotherapy: gastrointestinal tolerability, treatment discontinuation, the absence of an active comparator, unexpectedly high placebo-associated weight loss and limited outcome data. Thus, SYNCHRONIZE™-1 should be read as an important proof of principle for dual glucagon-GLP-1 receptor agonism rather than as a definitive positioning of the therapy within the treatment landscape. The next challenge is to determine whether this mechanism delivers durable cardiovascular, renal, and hepatic benefits, and in which patient populations.
The therapeutic landscape for obesity is changing rapidly, driven by the recognition of obesity as a chronic, biologically heterogeneous disease, with clinically relevant organ consequences. In this context, the phase 3 SYNCHRONIZE™-1 trial of survodutide, a once-weekly dual agonist of glucagon receptor and glucagon-like peptide 1 (GLP-1) receptor, is notable not simply because it adds another effective incretin-based therapy, but because it tests a broader metabolic concept. By pairing GLP-1-mediated appetite suppression with glucagon-mediated effects on energy expenditure and hepatic lipid handling, survodutide aims to extend treatment beyond appetite control towards coordinated modulation of adiposity, cardiometabolic risk and steatotic liver disease. In adults with obesity without diabetes, SYNCHRONIZE™-1 showed sustained body-weight reductions of approximately 12–13% over 76 weeks, compared with 5.4% with placebo, and increased the proportion of participants achieving clinically ambitious weight-loss thresholds, including at least 20% weight loss. Improvements in waist circumference, glycemic and lipid measures, together with reductions in visceral and liver fat content (LFC) in imaging analyses, support the possibility of benefits that are metabolically broader than scale weight alone. Yet the trial also illustrates familiar tensions in obesity pharmacotherapy: gastrointestinal tolerability, treatment discontinuation, the absence of an active comparator, unexpectedly high placebo-associated weight loss and limited outcome data. Thus, SYNCHRONIZE™-1 should be read as an important proof of principle for dual glucagon-GLP-1 receptor agonism rather than as a definitive positioning of the therapy within the treatment landscape. The next challenge is to determine whether this mechanism delivers durable cardiovascular, renal, and hepatic benefits, and in which patient populations.
DOI: https://doi.org/10.37349/eds.2026.1008175
Cancer treatment faces severe challenges such as drug resistance, side effects, and high costs. The “repurposing old drugs” strategy, which involves repositioning approved drugs for non-oncology indications for cancer treatment, has opened up new avenues for developing efficient, low-toxicity, and rapidly translatable combination therapies. This strategy can not only accelerate clinical translation by leveraging known pharmacological and safety data but also generate synergistic effects with standard chemotherapy, targeted therapy, or immunotherapy by targeting non-classical pathways such as the tumor microenvironment, metabolic reprogramming, and epigenetic regulation. This paper aims to systematically review the repositioning strategies of non-oncology drugs in cancer combination therapies, focusing on their mechanisms of action, synergistic principles, high-throughput screening and computational prediction methods, as well as pre-clinical and clinical research progress based on models such as patient-derived organoids. The paper systematically analyzes the synergistic effects and potential of representative drugs such as metformin, statins, antimalarials, antipsychotics, non-steroidal anti-inflammatory drugs, β-blockers, antihistamines, and cardiovascular drugs. It also summarizes the current challenges in drug screening, mechanism validation, commercial incentives, clinical trial design, and safety re-evaluation, aiming to provide a theoretical basis and future research directions for optimizing cancer combination treatment strategies.
Cancer treatment faces severe challenges such as drug resistance, side effects, and high costs. The “repurposing old drugs” strategy, which involves repositioning approved drugs for non-oncology indications for cancer treatment, has opened up new avenues for developing efficient, low-toxicity, and rapidly translatable combination therapies. This strategy can not only accelerate clinical translation by leveraging known pharmacological and safety data but also generate synergistic effects with standard chemotherapy, targeted therapy, or immunotherapy by targeting non-classical pathways such as the tumor microenvironment, metabolic reprogramming, and epigenetic regulation. This paper aims to systematically review the repositioning strategies of non-oncology drugs in cancer combination therapies, focusing on their mechanisms of action, synergistic principles, high-throughput screening and computational prediction methods, as well as pre-clinical and clinical research progress based on models such as patient-derived organoids. The paper systematically analyzes the synergistic effects and potential of representative drugs such as metformin, statins, antimalarials, antipsychotics, non-steroidal anti-inflammatory drugs, β-blockers, antihistamines, and cardiovascular drugs. It also summarizes the current challenges in drug screening, mechanism validation, commercial incentives, clinical trial design, and safety re-evaluation, aiming to provide a theoretical basis and future research directions for optimizing cancer combination treatment strategies.
DOI: https://doi.org/10.37349/eds.2026.1008176
This article belongs to the special issue Drug Repurposing: Accelerating Cancer Therapeutic Discoveries
Breast cancer management increasingly hinges on decisions made in “grey zones” where tissue sampling is scarce, and tumour biology evolves under therapeutic pressure. This narrative review synthesises evidence on how whole-body imaging biomarkers and circulating tumour DNA (ctDNA) can support response-adaptive pathways at the interface of surgical and systemic care. Four clinically actionable domains are discussed. (a) 16α-[18F]fluoro-17β-estradiol ([18F]FES) positron emission tomography/computed tomography (PET/CT) enables non-invasive, whole-body mapping of functional oestrogen receptor (ER) expression to address receptor discordance, heterogeneous metastases, and selection of endocrine-based strategies. (b) Human epidermal growth factor receptor 2 (HER2)-targeted PET (notably 89Zr-trastuzumab, with emerging alternatives) provides whole-body receptor assessment to uncover actionable HER2-positive disease despite HER2-negative primaries, informing anti-HER2 treatment selection when repeat biopsy is infeasible. (c) In triple-negative breast cancer treated with immune checkpoint inhibitors, 18F-fluorodeoxyglucose (18F-FDG) PET/CT offers quantitative response and whole-body burden assessment but requires immunotherapy-aware interpretation (e.g., confirmation strategies for apparent early progression) to mitigate pseudoprogression and dissociated responses, while simultaneously visualising immune-related adverse events. (d) Pairing early metabolic change on FDG PET/CT with ctDNA kinetics is presented as a biologically complementary approach for response monitoring and risk stratification, with potential to inform trial-embedded response-adaptive hypotheses, with ctDNA offering a rapid systemic trajectory and PET providing lesion-level localisation in heterogeneous or oligoprogressive disease. Overall, these tools add value only when linked to prespecified clinical questions and consensus actions; prospective studies are needed to validate standardised, outcome-improving response-adaptive algorithms that integrate imaging and liquid biopsy. Key implementation challenges include tracer availability, harmonised acquisition/reconstruction, threshold definition, and avoiding overtesting. Near-term impact may be greatest in problem-solving and in trial-embedded decision rules that operationalise biomarker-guided care.
Breast cancer management increasingly hinges on decisions made in “grey zones” where tissue sampling is scarce, and tumour biology evolves under therapeutic pressure. This narrative review synthesises evidence on how whole-body imaging biomarkers and circulating tumour DNA (ctDNA) can support response-adaptive pathways at the interface of surgical and systemic care. Four clinically actionable domains are discussed. (a) 16α-[18F]fluoro-17β-estradiol ([18F]FES) positron emission tomography/computed tomography (PET/CT) enables non-invasive, whole-body mapping of functional oestrogen receptor (ER) expression to address receptor discordance, heterogeneous metastases, and selection of endocrine-based strategies. (b) Human epidermal growth factor receptor 2 (HER2)-targeted PET (notably 89Zr-trastuzumab, with emerging alternatives) provides whole-body receptor assessment to uncover actionable HER2-positive disease despite HER2-negative primaries, informing anti-HER2 treatment selection when repeat biopsy is infeasible. (c) In triple-negative breast cancer treated with immune checkpoint inhibitors, 18F-fluorodeoxyglucose (18F-FDG) PET/CT offers quantitative response and whole-body burden assessment but requires immunotherapy-aware interpretation (e.g., confirmation strategies for apparent early progression) to mitigate pseudoprogression and dissociated responses, while simultaneously visualising immune-related adverse events. (d) Pairing early metabolic change on FDG PET/CT with ctDNA kinetics is presented as a biologically complementary approach for response monitoring and risk stratification, with potential to inform trial-embedded response-adaptive hypotheses, with ctDNA offering a rapid systemic trajectory and PET providing lesion-level localisation in heterogeneous or oligoprogressive disease. Overall, these tools add value only when linked to prespecified clinical questions and consensus actions; prospective studies are needed to validate standardised, outcome-improving response-adaptive algorithms that integrate imaging and liquid biopsy. Key implementation challenges include tracer availability, harmonised acquisition/reconstruction, threshold definition, and avoiding overtesting. Near-term impact may be greatest in problem-solving and in trial-embedded decision rules that operationalise biomarker-guided care.
DOI: https://doi.org/10.37349/etat.2026.1002398
This article belongs to the special issue Breaking Boundaries in Breast Cancer Care: Emerging Controversies and Innovation in Surgical and Medical Approaches
Breast cancer survival is shaped by a complex interaction of tumor-specific, biological, and patient-related factors. Stage at diagnosis remains the strongest predictor of outcome. Tumor size, nodal involvement, and histologic grade further aid in prognostic prediction by reflecting the biological aggressiveness of the disease. Since the early 2000s, molecular characteristics gained importance in risk stratification. Hormone receptor-positive cancers generally respond well to endocrine therapy, while HER2-positive tumors, once associated with poor outcomes, now benefit from targeted therapy. Newer agents and combinations such as CDK4/6 and PI3K/AKT/mTOR inhibitors are being investigated recently. Patient factors, including age, comorbidities, and overall health, also influence outcome and treatment tolerance. Cardiovascular toxicity from chemotherapy and radiotherapy has become an important consideration, particularly in the elderly. Although modern radiotherapy techniques have reduced cardiac risks, long-term cardiovascular mortality remains a competing cause of death in many survivors. Studies comparing breast-conserving therapy with mastectomy suggest improved overall survival with the former, partly due to reduced treatment morbidity. Early detection through mammography, ultrasound, and awareness campaigns greatly improves survival, yet access remains unequal in low-resource settings. Strengthening healthcare systems, tailoring treatments, expanding multidisciplinary care and improving public education are essential. Affordable personalized therapies, better infrastructure, and international collaboration can reduce disparities and enhance global breast cancer outcomes. Our international team researched literature information as well as summarizing up-to-date opinions from global experts, including those with limited resources and war-torn regions.
Breast cancer survival is shaped by a complex interaction of tumor-specific, biological, and patient-related factors. Stage at diagnosis remains the strongest predictor of outcome. Tumor size, nodal involvement, and histologic grade further aid in prognostic prediction by reflecting the biological aggressiveness of the disease. Since the early 2000s, molecular characteristics gained importance in risk stratification. Hormone receptor-positive cancers generally respond well to endocrine therapy, while HER2-positive tumors, once associated with poor outcomes, now benefit from targeted therapy. Newer agents and combinations such as CDK4/6 and PI3K/AKT/mTOR inhibitors are being investigated recently. Patient factors, including age, comorbidities, and overall health, also influence outcome and treatment tolerance. Cardiovascular toxicity from chemotherapy and radiotherapy has become an important consideration, particularly in the elderly. Although modern radiotherapy techniques have reduced cardiac risks, long-term cardiovascular mortality remains a competing cause of death in many survivors. Studies comparing breast-conserving therapy with mastectomy suggest improved overall survival with the former, partly due to reduced treatment morbidity. Early detection through mammography, ultrasound, and awareness campaigns greatly improves survival, yet access remains unequal in low-resource settings. Strengthening healthcare systems, tailoring treatments, expanding multidisciplinary care and improving public education are essential. Affordable personalized therapies, better infrastructure, and international collaboration can reduce disparities and enhance global breast cancer outcomes. Our international team researched literature information as well as summarizing up-to-date opinions from global experts, including those with limited resources and war-torn regions.
DOI: https://doi.org/10.37349/emed.2026.1001423
The human gut microbiota plays a critical role in regulating host health and disease, making it a key target for the development of targeted microbial therapies. This review focuses on designer probiotics and synbiotics, which are genetically engineered microorganisms used in combination with prebiotics to modulate the gut microbiota and support personalised health outcomes. Unlike conventional probiotics, these engineered strains are designed to perform specific metabolic or signalling functions, thereby enhancing colonisation efficiency and functional efficacy. The article summarises recent advancements in systems biology, synthetic biology, and omics technologies (including genomics, proteomics, and metabolomics) that facilitate the design and optimisation of next-generation microbial formulations. Their significance lies in enabling precision nutrition and the development of functional foods tailored to individual host requirements. This review also discusses strategies for microbial strain engineering, synbiotic formulation, and the application of high-throughput omics approaches to better understand host-microbe interactions. Furthermore, it highlights applications in managing gut-related disorders and improving food quality. While addressing challenges such as biosafety concerns, regulatory limitations, and environmental implications, the review emphasises the potential of designer probiotics and synbiotics as innovative tools for precision-guided health through dietary interventions. Overall, this emerging field provides a sustainable approach to advancing nutrition and microbiome-based therapies by bridging precision health with food science.
The human gut microbiota plays a critical role in regulating host health and disease, making it a key target for the development of targeted microbial therapies. This review focuses on designer probiotics and synbiotics, which are genetically engineered microorganisms used in combination with prebiotics to modulate the gut microbiota and support personalised health outcomes. Unlike conventional probiotics, these engineered strains are designed to perform specific metabolic or signalling functions, thereby enhancing colonisation efficiency and functional efficacy. The article summarises recent advancements in systems biology, synthetic biology, and omics technologies (including genomics, proteomics, and metabolomics) that facilitate the design and optimisation of next-generation microbial formulations. Their significance lies in enabling precision nutrition and the development of functional foods tailored to individual host requirements. This review also discusses strategies for microbial strain engineering, synbiotic formulation, and the application of high-throughput omics approaches to better understand host-microbe interactions. Furthermore, it highlights applications in managing gut-related disorders and improving food quality. While addressing challenges such as biosafety concerns, regulatory limitations, and environmental implications, the review emphasises the potential of designer probiotics and synbiotics as innovative tools for precision-guided health through dietary interventions. Overall, this emerging field provides a sustainable approach to advancing nutrition and microbiome-based therapies by bridging precision health with food science.
DOI: https://doi.org/10.37349/eff.2026.1010182
Aim:
Allostatic load (AL) is a composite measure of cumulative physiological stress, but its role in heart failure (HF) onset and prognosis remains unclear.
Methods:
We analyzed data from two U.S. cohorts. Logistic regression assessed AL and incident HF in 3,814 adults from the Health and Retirement Study (HRS, 2016–2020). Cox regression examined AL with cardiovascular and all-cause mortality in 1,200 HF patients from the National Health and Nutrition Examination Survey (NHANES, 1999–2010 and 2015–2016). AL was derived from nine biomarkers and categorized as low (0–2), medium (3), or high (≥ 4).
Results:
In HRS, after full adjustment, high AL was associated with increased incident HF risk versus low AL (OR = 2.07; 95% CI: 1.29–3.32; P = 0.002), with each 1-unit increase raising risk by 30% (P < 0.001). In NHANES, after full adjustment, high AL predicted elevated cardiovascular (HR = 2.03; 95% CI: 1.37–3.03; P < 0.001) and all-cause mortality (HR = 1.70; 95% CI: 1.30–2.22; P < 0.001). Per unit increase, AL raised cardiovascular mortality by 18% and all-cause mortality by 15%. Model performance improved modestly with AL.
Conclusions:
Elevated AL is independently associated with HF incidence and poorer prognosis, supporting its potential as an integrative biomarker for HF risk stratification and prevention.
Aim:
Allostatic load (AL) is a composite measure of cumulative physiological stress, but its role in heart failure (HF) onset and prognosis remains unclear.
Methods:
We analyzed data from two U.S. cohorts. Logistic regression assessed AL and incident HF in 3,814 adults from the Health and Retirement Study (HRS, 2016–2020). Cox regression examined AL with cardiovascular and all-cause mortality in 1,200 HF patients from the National Health and Nutrition Examination Survey (NHANES, 1999–2010 and 2015–2016). AL was derived from nine biomarkers and categorized as low (0–2), medium (3), or high (≥ 4).
Results:
In HRS, after full adjustment, high AL was associated with increased incident HF risk versus low AL (OR = 2.07; 95% CI: 1.29–3.32; P = 0.002), with each 1-unit increase raising risk by 30% (P < 0.001). In NHANES, after full adjustment, high AL predicted elevated cardiovascular (HR = 2.03; 95% CI: 1.37–3.03; P < 0.001) and all-cause mortality (HR = 1.70; 95% CI: 1.30–2.22; P < 0.001). Per unit increase, AL raised cardiovascular mortality by 18% and all-cause mortality by 15%. Model performance improved modestly with AL.
Conclusions:
Elevated AL is independently associated with HF incidence and poorer prognosis, supporting its potential as an integrative biomarker for HF risk stratification and prevention.
DOI: https://doi.org/10.37349/ec.2026.1012118
Aim:
Telemonitoring apps are increasingly prescribed as part of self-management for patients with Chronic Obstructive Pulmonary Disease (COPD), yet patients still make minimal use of these apps. This research investigates explanatory factors associated with the behavioral intention to use and actual use of COPD telemonitoring apps among users and non-users.
Methods:
A cross-sectional study was conducted among 200 COPD patients from two Dutch hospitals. Eligible participants (≥ 18 years, diagnosed with COPD, ≥ 2 outpatient pulmonology visits in 2023) were identified through the electronic health record and invited by mail. Participants completed a self-administered questionnaire assessing demographics, disease severity, literacy, facilitating conditions, and app-related factors, based on the Unified Theory of Acceptance and Use of Technology 2 (UTAUT2), the Technology Acceptance Model (TAM), and the Reasoned Action Approach (RAA). Behavioral intention was analyzed using hierarchical multiple regression, and use was analyzed using binomial logistic regression.
Results:
Intention was explained by performance expectancy (coefficient = 0.760, p ≤ 0.001), self-efficacy (coefficient = 0.207, p = 0.009), and alignment with personal norms and values (coefficient = 0.163, p = 0.006). Use was explained by self-efficacy (OR = 1.992, p = 0.023), social influence (OR = 1.642, p = 0.039), personalization (OR = 0.628, p = 0.039), and intention to use (OR = 3.459, p ≤ 0.001). App users showed significantly higher digital literacy, performance expectancy, and fewer symptoms compared to non-users. Users also experienced significantly higher importance of social influence and alignment with norms and values than non-users. Demographic variables and disease severity were no significant predictors of behavioral intention and use.
Conclusions:
Optimizing the app and the supportive role of the healthcare professional, enhancing digital and health literacy, and hybrid care ensures that patients can benefit from both traditional care and the advantages of remote monitoring.
Aim:
Telemonitoring apps are increasingly prescribed as part of self-management for patients with Chronic Obstructive Pulmonary Disease (COPD), yet patients still make minimal use of these apps. This research investigates explanatory factors associated with the behavioral intention to use and actual use of COPD telemonitoring apps among users and non-users.
Methods:
A cross-sectional study was conducted among 200 COPD patients from two Dutch hospitals. Eligible participants (≥ 18 years, diagnosed with COPD, ≥ 2 outpatient pulmonology visits in 2023) were identified through the electronic health record and invited by mail. Participants completed a self-administered questionnaire assessing demographics, disease severity, literacy, facilitating conditions, and app-related factors, based on the Unified Theory of Acceptance and Use of Technology 2 (UTAUT2), the Technology Acceptance Model (TAM), and the Reasoned Action Approach (RAA). Behavioral intention was analyzed using hierarchical multiple regression, and use was analyzed using binomial logistic regression.
Results:
Intention was explained by performance expectancy (coefficient = 0.760, p ≤ 0.001), self-efficacy (coefficient = 0.207, p = 0.009), and alignment with personal norms and values (coefficient = 0.163, p = 0.006). Use was explained by self-efficacy (OR = 1.992, p = 0.023), social influence (OR = 1.642, p = 0.039), personalization (OR = 0.628, p = 0.039), and intention to use (OR = 3.459, p ≤ 0.001). App users showed significantly higher digital literacy, performance expectancy, and fewer symptoms compared to non-users. Users also experienced significantly higher importance of social influence and alignment with norms and values than non-users. Demographic variables and disease severity were no significant predictors of behavioral intention and use.
Conclusions:
Optimizing the app and the supportive role of the healthcare professional, enhancing digital and health literacy, and hybrid care ensures that patients can benefit from both traditional care and the advantages of remote monitoring.
DOI: https://doi.org/10.37349/edht.2026.1011101
With the rising global prevalence of obesity and type 2 diabetes, metabolic disorders have become major drivers of cardiovascular morbidity and mortality worldwide. Cardiovascular-kidney-metabolic (CKM) syndrome encompasses obesity, type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and cardiovascular disease (CVD), all of which share common pathophysiological pathways. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), a novel class of antihyperglycemic agents, have demonstrated pleiotropic effects—including weight reduction, blood pressure lowering, albuminuria reduction, decreased major adverse cardiovascular events (MACE), and slowed progression of renal dysfunction. These benefits position GLP-1RAs as a potential cornerstone therapy for CKM syndrome. This review synthesizes recent advances in GLP-1RA research within the CKM framework, explores their underlying mechanisms, and offers insights to refine diagnostic and therapeutic strategies for cardiometabolic diseases.
With the rising global prevalence of obesity and type 2 diabetes, metabolic disorders have become major drivers of cardiovascular morbidity and mortality worldwide. Cardiovascular-kidney-metabolic (CKM) syndrome encompasses obesity, type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and cardiovascular disease (CVD), all of which share common pathophysiological pathways. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), a novel class of antihyperglycemic agents, have demonstrated pleiotropic effects—including weight reduction, blood pressure lowering, albuminuria reduction, decreased major adverse cardiovascular events (MACE), and slowed progression of renal dysfunction. These benefits position GLP-1RAs as a potential cornerstone therapy for CKM syndrome. This review synthesizes recent advances in GLP-1RA research within the CKM framework, explores their underlying mechanisms, and offers insights to refine diagnostic and therapeutic strategies for cardiometabolic diseases.
DOI: https://doi.org/10.37349/eemd.2026.101481
Climate change (CC) affects our health in ways especially when it comes to liver diseases. Rising temperatures and changing weather patterns are altering the spread and severity of liver diseases. CC can affect health, especially liver diseases, in direct and indirect ways. Hepatic infections such as viral hepatitis and schistosomiasis, metabolic dysfunction-associated steatotic liver disease (MASLD), hepatocellular carcinoma, and acute on chronic liver failure (ACLF) are examples. The movement of infected individuals from areas where diseases are endemic, prompted by ecological disasters, introduces these diseases to previously unexposed regions. CC serves as an early warning for shifts and the necessity to re-evaluate hepatic diseases, which is crucial for health policymakers. Ambient temperature and its variability have a major influence on the pathogenesis of MASLD, demonstrating nonlinear exposure–response relationships. Long-term temperature exposure follows a reverse J-shaped pattern, while temperature variability shows a U-shaped association, with both extremes independently increasing disease susceptibility. Prolonged exposure to cold and fluctuations in temperature could worsen various liver diseases. Gaining a deeper insight into these CC-related risks for our patients and practice is essential to optimize their care both now and in the warmer temperatures ahead. Incorporating climate resilience into public health initiatives may aid in alleviating the growing prevalence of liver diseases linked to CC. Aside from increasing awareness, which should take precedence, there is a pressing need to investigate innovative ways to frame the educational message and eliminate financial incentives that contribute to environmental damage. Common climate strategies for healthcare systems include reducing and managing waste, utilizing cleaner and less energy, offering and endorsing planet-friendly food options, and addressing transportation issues related to accessing healthcare facilities, such as transitioning in-person appointments to virtual consultations when possible, encouraging green-endoscopy practices, and participating in conferences virtually can be beneficial.
Climate change (CC) affects our health in ways especially when it comes to liver diseases. Rising temperatures and changing weather patterns are altering the spread and severity of liver diseases. CC can affect health, especially liver diseases, in direct and indirect ways. Hepatic infections such as viral hepatitis and schistosomiasis, metabolic dysfunction-associated steatotic liver disease (MASLD), hepatocellular carcinoma, and acute on chronic liver failure (ACLF) are examples. The movement of infected individuals from areas where diseases are endemic, prompted by ecological disasters, introduces these diseases to previously unexposed regions. CC serves as an early warning for shifts and the necessity to re-evaluate hepatic diseases, which is crucial for health policymakers. Ambient temperature and its variability have a major influence on the pathogenesis of MASLD, demonstrating nonlinear exposure–response relationships. Long-term temperature exposure follows a reverse J-shaped pattern, while temperature variability shows a U-shaped association, with both extremes independently increasing disease susceptibility. Prolonged exposure to cold and fluctuations in temperature could worsen various liver diseases. Gaining a deeper insight into these CC-related risks for our patients and practice is essential to optimize their care both now and in the warmer temperatures ahead. Incorporating climate resilience into public health initiatives may aid in alleviating the growing prevalence of liver diseases linked to CC. Aside from increasing awareness, which should take precedence, there is a pressing need to investigate innovative ways to frame the educational message and eliminate financial incentives that contribute to environmental damage. Common climate strategies for healthcare systems include reducing and managing waste, utilizing cleaner and less energy, offering and endorsing planet-friendly food options, and addressing transportation issues related to accessing healthcare facilities, such as transitioning in-person appointments to virtual consultations when possible, encouraging green-endoscopy practices, and participating in conferences virtually can be beneficial.
DOI: https://doi.org/10.37349/edd.2026.1005131
Obesity is a rapidly growing global health concern. The pathogenesis is complex and cannot be fully explained by lifestyle factors alone. The increasing attention towards this concern has finally been directed towards environmental contributors which may influence metabolic regulation. Microplastics and nano-plastics (MNPs) are ubiquitous environmental pollutants that have recently been detected in food, drinking water, air, and human biological samples, raising concerns about their potential role in metabolic disorders, including obesity. Chronic exposure to MNPs may interfere with metabolic homeostasis through multiple biological pathways. Emerging evidence, including both experimental and animal studies, reports alterations in lipid metabolism, body weight, insulin sensitivity, and inflammatory responses following MNPs exposure. This review synthesizes current evidence linking MNPs to obesity, highlighting key exposure pathways, mechanistic insights, and gaps in existing research. Understanding the metabolic implications of MNPs exposure is essential for advancing obesity research and informing future public health strategies. Further well-designed human studies are needed to clarify causal relationships and guide preventive interventions.
Obesity is a rapidly growing global health concern. The pathogenesis is complex and cannot be fully explained by lifestyle factors alone. The increasing attention towards this concern has finally been directed towards environmental contributors which may influence metabolic regulation. Microplastics and nano-plastics (MNPs) are ubiquitous environmental pollutants that have recently been detected in food, drinking water, air, and human biological samples, raising concerns about their potential role in metabolic disorders, including obesity. Chronic exposure to MNPs may interfere with metabolic homeostasis through multiple biological pathways. Emerging evidence, including both experimental and animal studies, reports alterations in lipid metabolism, body weight, insulin sensitivity, and inflammatory responses following MNPs exposure. This review synthesizes current evidence linking MNPs to obesity, highlighting key exposure pathways, mechanistic insights, and gaps in existing research. Understanding the metabolic implications of MNPs exposure is essential for advancing obesity research and informing future public health strategies. Further well-designed human studies are needed to clarify causal relationships and guide preventive interventions.
DOI: https://doi.org/10.37349/edd.2026.1005130
Pembrolizumab, a programmed cell death protein 1 inhibitor, has had a substantial impact on cancer treatment across multiple malignancies, but is associated with immune-related cardiovascular toxicities that pose significant clinical challenges. Complications such as myocarditis, arrhythmias, and cardiomyopathy are emerging as significant entities with high morbidity and mortality. This article is a narrative review and was not designed or conducted as a systematic review. No formal systematic review protocol was followed and attempts to identify or include all published studies on this topic were not undertaken. The goal is to provide a clinically oriented synthesis of the current literature on pembrolizumab-associated cardiotoxicity. A literature search was conducted using PubMed, Medline, and Google Scholar databases for articles published between January 2014 and March 2025. Search terms included ‘pembrolizumab,’ ‘PD-1 inhibitor,’ ‘immune checkpoint inhibitor,’ ‘cardiotoxicity,’ ‘myocarditis,’ ‘pericarditis,’ ‘arrhythmia,’ and ‘cardiac adverse events,’ used individually and in combination. Inclusion criteria encompassed English-language clinical trials, observational studies, systematic reviews, meta-analyses, pharmacovigilance analyses, clinical practice guidelines, and case reports involving human subjects. Non-English publications, preclinical studies without clinical correlates, and editorials without original data were excluded. Reference lists of identified articles were manually reviewed to identify additional relevant publications. Study selection was performed by a single author. Pembrolizumab-induced myocarditis, although rare, carries a high mortality rate and typically presents within the first few weeks of treatment, including a relative risk of myocarditis ~4.5 with combination immune checkpoint inhibitor therapy. Proposed mechanisms of this cardiotoxicity, though not settled, include shared antigenic targets between tumor and cardiac tissue and impaired immune tolerance. Current management relies on prompt recognition, immunosuppression with high-dose IV methylprednisolone as first-line therapy, and additional immunomodulatory agents for refractory cases. Emerging evidence from case reports and small cohort studies suggests potential benefit from abatacept with ruxolitinib in steroid-refractory cases; however, prospective validation is needed. Baseline cardiac screening and serial monitoring of cardiac biomarkers including high-sensitivity troponin and NT-proBNP, and a multidisciplinary cardio-oncology approach are essential for early detection and optimal outcomes.
Pembrolizumab, a programmed cell death protein 1 inhibitor, has had a substantial impact on cancer treatment across multiple malignancies, but is associated with immune-related cardiovascular toxicities that pose significant clinical challenges. Complications such as myocarditis, arrhythmias, and cardiomyopathy are emerging as significant entities with high morbidity and mortality. This article is a narrative review and was not designed or conducted as a systematic review. No formal systematic review protocol was followed and attempts to identify or include all published studies on this topic were not undertaken. The goal is to provide a clinically oriented synthesis of the current literature on pembrolizumab-associated cardiotoxicity. A literature search was conducted using PubMed, Medline, and Google Scholar databases for articles published between January 2014 and March 2025. Search terms included ‘pembrolizumab,’ ‘PD-1 inhibitor,’ ‘immune checkpoint inhibitor,’ ‘cardiotoxicity,’ ‘myocarditis,’ ‘pericarditis,’ ‘arrhythmia,’ and ‘cardiac adverse events,’ used individually and in combination. Inclusion criteria encompassed English-language clinical trials, observational studies, systematic reviews, meta-analyses, pharmacovigilance analyses, clinical practice guidelines, and case reports involving human subjects. Non-English publications, preclinical studies without clinical correlates, and editorials without original data were excluded. Reference lists of identified articles were manually reviewed to identify additional relevant publications. Study selection was performed by a single author. Pembrolizumab-induced myocarditis, although rare, carries a high mortality rate and typically presents within the first few weeks of treatment, including a relative risk of myocarditis ~4.5 with combination immune checkpoint inhibitor therapy. Proposed mechanisms of this cardiotoxicity, though not settled, include shared antigenic targets between tumor and cardiac tissue and impaired immune tolerance. Current management relies on prompt recognition, immunosuppression with high-dose IV methylprednisolone as first-line therapy, and additional immunomodulatory agents for refractory cases. Emerging evidence from case reports and small cohort studies suggests potential benefit from abatacept with ruxolitinib in steroid-refractory cases; however, prospective validation is needed. Baseline cardiac screening and serial monitoring of cardiac biomarkers including high-sensitivity troponin and NT-proBNP, and a multidisciplinary cardio-oncology approach are essential for early detection and optimal outcomes.
DOI: https://doi.org/10.37349/ec.2026.1012117
Autism spectrum disorder (ASD) is a clinically heterogeneous neurodevelopmental condition characterized by core social communication deficits and restricted/repetitive behaviors. The majority of cases present with certain medical and psychiatric comorbidities. These include epilepsy, gastrointestinal disorders, attention-deficit/hyperactivity disorder, anxiety, and metabolic dysregulation. While animal models are indispensable in pre-clinical research and studying ASD’s pathobiology, there remains a need to address these comorbidities while modelling major ASD clinical domains. The paper describes a spectrum of animal models for ASD and its comorbid disorders, with a focus on ASD & epilepsy co-occurrence.
Autism spectrum disorder (ASD) is a clinically heterogeneous neurodevelopmental condition characterized by core social communication deficits and restricted/repetitive behaviors. The majority of cases present with certain medical and psychiatric comorbidities. These include epilepsy, gastrointestinal disorders, attention-deficit/hyperactivity disorder, anxiety, and metabolic dysregulation. While animal models are indispensable in pre-clinical research and studying ASD’s pathobiology, there remains a need to address these comorbidities while modelling major ASD clinical domains. The paper describes a spectrum of animal models for ASD and its comorbid disorders, with a focus on ASD & epilepsy co-occurrence.
DOI: https://doi.org/10.37349/en.2026.1006145
This article belongs to the special issue Advances in Epilepsy Research
Precision oncology has revolutionized cancer care in high-income countries, but its implementation in Latin American low-resource settings faces profound bioethical dilemmas. This study analyzes these challenges through the lens of social justice and equity. An integrative review was conducted following the Whittemore and Knafl framework. A systematic search was performed across PubMed, Scopus, SciELO, and LILACS (2015–2025). Thematic synthesis was applied to integrate empirical data with normative bioethical theories. Four major analytical themes were identified: 1) The innovation paradox and financial toxicity, where prohibitive pricing (exceeding 100,000 USD/year) violates distributive justice and leads to a biological penalty in survival; 2) Infrastructure deficits and epistemic injustice, highlighted by a 9.4% access rate to next-generation sequencing (NGS) and the risks of applying Eurocentric genomic data to admixed LA populations; 3) Research vulnerability, where clinical trials serve as survival strategies, compromising autonomy and informed consent; and 4) The judicialization dilemma, where individual court orders for high-cost drugs threaten systemic sustainability and equity. To prevent a genomic apartheid, Latin America must transition toward genomic sovereignty and frugal precision oncology. Bioethical frameworks in the region must prioritize protection ethics and social justice to ensure that scientific innovation does not exacerbate existing health inequities.
Precision oncology has revolutionized cancer care in high-income countries, but its implementation in Latin American low-resource settings faces profound bioethical dilemmas. This study analyzes these challenges through the lens of social justice and equity. An integrative review was conducted following the Whittemore and Knafl framework. A systematic search was performed across PubMed, Scopus, SciELO, and LILACS (2015–2025). Thematic synthesis was applied to integrate empirical data with normative bioethical theories. Four major analytical themes were identified: 1) The innovation paradox and financial toxicity, where prohibitive pricing (exceeding 100,000 USD/year) violates distributive justice and leads to a biological penalty in survival; 2) Infrastructure deficits and epistemic injustice, highlighted by a 9.4% access rate to next-generation sequencing (NGS) and the risks of applying Eurocentric genomic data to admixed LA populations; 3) Research vulnerability, where clinical trials serve as survival strategies, compromising autonomy and informed consent; and 4) The judicialization dilemma, where individual court orders for high-cost drugs threaten systemic sustainability and equity. To prevent a genomic apartheid, Latin America must transition toward genomic sovereignty and frugal precision oncology. Bioethical frameworks in the region must prioritize protection ethics and social justice to ensure that scientific innovation does not exacerbate existing health inequities.
DOI: https://doi.org/10.37349/etat.2026.1002397
Primary bone sarcomas are rare and biologically heterogeneous malignancies for which therapeutic progress remains limited, particularly in metastatic and recurrent disease. Advances in genomic and molecular profiling have revealed substantial inter- and intratumoral heterogeneity across the major subtypes, including osteosarcoma, Ewing sarcoma and chondrosarcoma, challenging conventional histology-driven treatment strategies. Precision medicine approaches are being increasingly explored to better capture this biological complexity and guide individualized therapeutic decision-making. This review examines emerging precision oncology strategies in bone sarcomas, including molecular diagnostics, targeted therapeutic approaches, three-dimensional functional modeling systems, and liquid biopsy technologies for dynamic disease monitoring. Together, these platforms provide biologically informed frameworks for patient-specific treatment and longitudinal assessment of tumor evolution. However, clinical implementation remains limited by genomic complexity, small patient cohorts, and methodological variability across experimental platforms. The integration of multi-layered precision models combining genomic stratification, functional drug sensitivity testing and circulating biomarker monitoring may enable more adaptive and individualized management strategies. Such approaches have the potential to improve therapeutic selection and ultimately advance outcomes for patients with primary bone sarcomas.
Primary bone sarcomas are rare and biologically heterogeneous malignancies for which therapeutic progress remains limited, particularly in metastatic and recurrent disease. Advances in genomic and molecular profiling have revealed substantial inter- and intratumoral heterogeneity across the major subtypes, including osteosarcoma, Ewing sarcoma and chondrosarcoma, challenging conventional histology-driven treatment strategies. Precision medicine approaches are being increasingly explored to better capture this biological complexity and guide individualized therapeutic decision-making. This review examines emerging precision oncology strategies in bone sarcomas, including molecular diagnostics, targeted therapeutic approaches, three-dimensional functional modeling systems, and liquid biopsy technologies for dynamic disease monitoring. Together, these platforms provide biologically informed frameworks for patient-specific treatment and longitudinal assessment of tumor evolution. However, clinical implementation remains limited by genomic complexity, small patient cohorts, and methodological variability across experimental platforms. The integration of multi-layered precision models combining genomic stratification, functional drug sensitivity testing and circulating biomarker monitoring may enable more adaptive and individualized management strategies. Such approaches have the potential to improve therapeutic selection and ultimately advance outcomes for patients with primary bone sarcomas.
DOI: https://doi.org/10.37349/etat.2026.1002396
This article belongs to the special issue Precision Oncology: Molecular Classification, Efficacy Prediction, and Treatment Decision-Making
