Current Oncology Reports最新文献

{"title":"From Symptom Control to Precision Supportive Oncology: Integrating Artificial Intelligence in Supportive Oncology for Gastrointestinal Cancers.","authors":"Arunkumar Krishnan, Mellar P Davis, Kunal C Kadakia","doi":"10.1007/s11912-026-01810-6","DOIUrl":"10.1007/s11912-026-01810-6","url":null,"abstract":"<p><strong>Purpose of review: </strong>Gastrointestinal (GI) cancers are among the most common malignancies worldwide and impose a substantial symptom burden from diagnosis through survivorship. Despite advances in systemic therapies and surgical approaches, patients continue to experience undertreated symptoms, psychosocial distress, financial toxicity, and fragmented supportive care. This review examines how artificial intelligence (AI) may help transform GI supportive oncology from a reactive, episodic model to a proactive, continuous, and personalized approach.</p><p><strong>Recent findings: </strong>AI applications in GI supportive oncology are advancing along two related domains: (1) AI-enabled patient-reported outcome (PRO) tools, including real-time symptom monitoring, unsupervised symptom clustering, and AI-enhanced triage pathways; and (2) tumor-aware supportive care, including AI-driven radiomics for sarcopenia detection and multimodal prognostic models that inform supportive care needs. Systematic electronic PRO monitoring has been associated with improved survival and reduced acute care utilization, while AI-automated CT sarcopenia detection identifies muscle wasting that routine clinical documentation often misses. Important implementation challenges remain, including the black-box problem, algorithmic bias, privacy concerns, the digital divide, and regulatory uncertainty. Precision supportive oncology, integrating PRO-based symptom intelligence with imaging-derived risk stratification, has the potential to improve GI cancer care by making it more anticipatory and patient-centered. This review proposes a two-lane framework consisting of PRO-driven symptom intelligence and tumor-aware supportive care, unified by principles of privacy, explainability, and equity. Responsible adoption will require prospective validation, equitable design, and clinically interpretable systems.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infectious Complications of Antibody-Drug Conjugates: A Review of Safety Data from FDA-Approved Agents.","authors":"Georgios Schinas, Pantazis-Michael Voutsinas, Dimitra Stefanou, Christos Stafylidis, Aikaterini Gkoufa, Dimitrios C Ziogas, Panagiotis T Diamantopoulos, Helen Gogas, Amalia Anastasopoulou","doi":"10.1007/s11912-026-01804-4","DOIUrl":"10.1007/s11912-026-01804-4","url":null,"abstract":"<p><strong>Purpose of review: </strong>With fifteen agents now FDA-approved and indications expanding into earlier treatment lines, antibody-drug conjugates (ADCs) represent a rapidly growing class of targeted cancer therapeutics. Despite their selective mechanism of action, infectious complications are clinically significant and have been flagged as a disproportionate safety signal in post-marketing surveillance. This review characterizes the infection risk profiles of all fifteen FDA-approved ADCs through systematic extraction of prescribing information and pivotal trial safety data, and examines the pathophysiological mechanisms, antigen-specific clinical patterns, and evidence-based prophylaxis strategies applicable to this class.</p><p><strong>Recent findings: </strong>Calicheamicin-based agents carry the highest infection burden, with grade ≥ 3 infection rates exceeding 30-47% and near-universal severe neutropenia. CD30- and CD79b-targeting vedotin conjugates are associated with opportunistic infections-including progressive multifocal leukoencephalopathy and Pneumocystis jirovecii pneumonia-through mechanisms beyond myelosuppression, particularly T-cell immune surveillance disruption and bystander-effect lymphotoxicity. Solid tumor ADCs demonstrate lower overall infection rates with distinct organ-specific patterns: genitourinary infections predominate with Nectin-4- and Tissue Factor-directed agents, whereas pulmonary events characterize HER2- and c-Met-targeted conjugates. Linker cleavability, drug-to-antibody ratio, and payload metabolism are identified as key pharmacological determinants of myelosuppressive and infectious risk. Infectious complications of ADC therapy are clinically significant but heterogeneous, with risk profiles primarily determined by target antigen, immunologic context, and concurrent treatment. These findings support the growing adoption of a combined prevention strategy incorporating disease-based risk stratification and drug-directed infection prophylaxis.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13354691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-Generation Checkpoint Combinations: Optimizing PD-(L)1-Based Therapy Across the Advanced, Adjuvant, and Neoadjuvant Settings.","authors":"Fausto Petrelli, Lara Colombo Zefinetti, Andrea D'Alessio, Lorenzo Dottorini, Antonio Ghidini","doi":"10.1007/s11912-026-01809-z","DOIUrl":"10.1007/s11912-026-01809-z","url":null,"abstract":"<p><strong>Purpose of review: </strong>Programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors are foundational components of therapy across many solid tumors, yet primary and acquired resistance limit durable benefit for a substantial proportion of patients. Rather than attempting a broad survey of every disease area, this review deliberately focuses on three tumor types in which PD-(L)1-based combinations have generated the most mature, practice-relevant evidence and in which the field is evolving most rapidly: renal cell carcinoma (RCC), urothelial (bladder) cancer, and non-small cell lung cancer (NSCLC). For each, we examine how combinations are being developed and positioned across the advanced, adjuvant, and neoadjuvant/perioperative settings, and we place selected cross-cutting strategies (dual checkpoint blockade, antibody-drug conjugates, hypoxia-inducible factor [HIF]-2α inhibition, and other partners) in that disease-specific context.</p><p><strong>Recent findings: </strong>In RCC, immune checkpoint inhibitor (ICI) plus vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) doublets are established first-line standards, adjuvant pembrolizumab is the first agent to improve both disease-free and overall survival after nephrectomy, and the HIF-2α inhibitor belzutifan has become a post-ICI/TKI option while being tested earlier in disease. In bladder cancer, the antibody-drug conjugate enfortumab vedotin combined with pembrolizumab has displaced platinum chemotherapy as first-line therapy for advanced disease, and perioperative durvalumab added to neoadjuvant chemotherapy improves event-free and overall survival in muscle-invasive disease. In NSCLC, neoadjuvant and perioperative chemoimmunotherapy regimens now demonstrate overall survival benefit, complementing established advanced-disease and adjuvant strategies. We also summarize combinations that have failed-most notably concurrent PD-(L)1 blockade with EGFR or ALK TKIs in oncogene-driven NSCLC, and anti-TIGIT antibodies in phase III-because these negative results are as instructive as the successes. Within RCC, bladder cancer, and NSCLC, next-generation PD-(L)1 combinations are reshaping treatment across all disease stages. The magnitude of benefit, the relevant biomarkers, and the toxicity trade-offs differ substantially by tumor type and by setting. Successful development depends on a sound biologic rationale, biomarker-informed patient selection, and careful toxicity management, and the evidence base remains uneven-ranging from mature phase III data to early signals-which we make explicit throughout.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the Immunological Landscape of Locoregional Therapies for Gastrointestinal Cancers: A Shift Toward Interventional Immuno-Oncology.","authors":"Augustin Suffisseau, Johanne Seguin, Katia Lemdani, Sarah Diakhaby, Claude Capron, Mostafa El Hajjam, Fabrice Ruiz, Frederique Peschaud, Nathalie Mignet, Robert Malafosse","doi":"10.1007/s11912-026-01807-1","DOIUrl":"10.1007/s11912-026-01807-1","url":null,"abstract":"<p><strong>Purpose of review: </strong>Locoregional therapies have emerged as key components in the therapeutic arsenal against gastrointestinal cancers, offering minimally invasive options with curative potential. Beyond their direct cytotoxic effects, these interventions can remodel the tumour microenvironment by inducing immunogenic cell death and initiating local and systemic immune responses, including abscopal effects. This review aims to examine how these immunomodulatory properties may support locoregional therapies as an ideal platform for intratumoural immunotherapy, positioning their combination at the core of the evolving field of interventional immuno-oncology.</p><p><strong>Recent findings: </strong>Recent studies demonstrate that locoregional therapies can induce immune responses through modulation of the tumour microenvironment, creating conditions that may be exploited by intratumoural immunotherapy. This review provides a comprehensive overview of current locoregional modalities, including thermal and non-thermal ablative techniques, transarterial therapies, and minimally invasive radiation methods, detailing their mechanisms of action, clinical applications, and immune-related effects. Special attention is given to emerging evidence supporting the combination of these approaches with intratumoural delivery of immunomodulatory agents, to enhance anticancer immune responses. The convergence of locoregional intervention and targeted immunomodulation represents an emerging therapeutic concept in the treatment of gastrointestinal cancers, offering the prospect of personalised, tumour-directed immune activation. This approach holds the potential to extend the benefits of immunotherapy beyond genetically defined subgroups to a broader patient population.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-PD-1 Combinations: Triplets and Beyond.","authors":"Claudia Trojaniello, Antonella Lucia Marretta, Bianca Arianna Facchini, Paolo Antonio Ascierto","doi":"10.1007/s11912-026-01788-1","DOIUrl":"10.1007/s11912-026-01788-1","url":null,"abstract":"<p><strong>Purpose of review: </strong>The advent of anti-PD-1 therapy has transformed the treatment paradigm of advanced melanoma, enabling durable responses in a proportion of patients. However, the impact of both primary and acquired resistance remains a significant barrier to sustained disease control. This review explores the biological rationale and clinical progress of anti-PD-1 based combination strategies, with a particular emphasis on emerging triplet regimens and next-generation immunotherapeutic approaches designed to extend survival and overcome resistance.</p><p><strong>Recent findings: </strong>While dual checkpoint inhibition (anti-PD-1 plus anti-CTLA-4 or anti-LAG-3) has improved clinical outcomes, further therapeutic advances are needed to expand the depth and durability of responses. Triplet combinations have shown promising activity in early-phase trials, with acceptable safety profiles. Promising triplet strategies currently under investigation include combinations of BRAF and MEK inhibitors with anti-PD-1 agents in BRAF-mutant melanoma, as well as regimens pairing anti-PD-1 therapy with emerging immunomodulatory agents. Biomarkers and disease control prior to infusion appear to be key determinants of outcome. Anti-PD-1-based triplet therapies represent a promising frontier in melanoma treatment. Future trials should define optimal combinations, patient selection, and therapeutic sequencing to maximize benefit and minimize toxicity.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sacituzumab Tirumotecan Across Gynecologic Malignancies: One Target, Multiple Diseases.","authors":"Amalia A Sofianidi, Evangelia Panagodimou, Emmanouil Kalampokas, Ioannis Georgakopoulos, Flora Zagouri","doi":"10.1007/s11912-026-01806-2","DOIUrl":"10.1007/s11912-026-01806-2","url":null,"abstract":"<p><strong>Purpose of review: </strong>Sacizuzumab Tirumotecan is a novel antibody-drug conjugate targeting TROP2 glycoprotein, which is highly expressed across malignant cells. Sacizuzumab Tirumotecan has already demonstrated promising clinical activity in combating breast and lung cancer, and it is currently under evaluation for use against gynecologic malignancies. This review aims to highlight the therapeutic potential of Sacituzumab Govitecan in gynecologic malignancies and to summarize the most recent evidence supporting its clinical application.</p><p><strong>Recent findings: </strong>Ongoing phase III trials of Sacituzumab Tirumotecan include cervical, ovarian, and endometrial cancers. Preliminary safety data of Sacituzumab Tirumotecan indicates a manageable toxicity profile, with the most commonly reported adverse events including hematologic toxicity, oral mucositis, and alopecia. Mature data from Phase III trials are anticipated to clarify the impact of Sacituzumab Tirumotecan on overall survival, progression-free survival, and objective response rates. Additionally, biomarker analyses may enhance patient selection strategies and refine prognostic assessment in gynecologic oncology.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clusterin in Head and Neck Squamous Cell Carcinoma: Diagnostic, Prognostic, and Therapeutic Implications.","authors":"Ashmita Das, Vinay Bisen, Yogita Dhurandhar, Surendra H Bodakhe, Ashok K Varma, Gauri Misra, Kamta P Namdeo","doi":"10.1007/s11912-026-01805-3","DOIUrl":"10.1007/s11912-026-01805-3","url":null,"abstract":"<p><strong>Purpose of review: </strong>Head and neck squamous cell carcinoma (HNSCC) is a global malignancy characterised by extremely low survival rates, primarily contributed to by late diagnosis, tumour heterogeneity, and resistance to available therapies. Deciphering reliable biomarkers is crucial for early diagnosis, prognosis and personalized therapy. This review discusses the possibilities of clusterin (CLU) as an emerging biomarker in the field of HNSCC therapeutics by incorporating insights derived from preclinical, clinical and proteomic data.</p><p><strong>Key findings: </strong>The expression of CLU in HNSCC cases has been found to be correlated with advanced stages of the tumour, metastatic potential higher histological grades and therapeutic resistance. Mechanistic studies demonstrate that CLU plays a dual role in enhancing tumour cell survival and facilitating apoptosis, contingent upon isoform and environmental context. Recent findings confirm the effectiveness of CLU as a biomarker for early diagnosis, risk evaluation, and forecasting therapeutic response. This review also focuses on the comparison of CLU to known HNSCC biomarkers and stresses the progress made in non-invasive screening and targeted therapies. In conclusion, CLU shows strong potential as a biomarker and therapeutic target, warranting further research for clinical application in HNSCC.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac Risk Without a Roadmap: Lack of Evidence-Based Guidance for Cardiovascular Toxicity of T-Cell Redirecting Therapies.","authors":"Serafino LaGalbo, Matthew T Foley, Anastasia E Metropulos, Kyle A Burton, Daniel R Principe","doi":"10.1007/s11912-026-01791-6","DOIUrl":"10.1007/s11912-026-01791-6","url":null,"abstract":"<p><strong>Purpose of review: </strong>T-cell redirecting therapies have revolutionized the treatment of several hematologic malignancies. These include CAR T-cell therapy, an adoptive immunotherapy in which a patient's T-cells are engineered to express synthetic receptors against tumor surface antigens, and bispecific T-cell engagers, antibodies simultaneously targeting CD3 and a tumor-specific antigen. Both approaches redirect T-cells toward tumor cells, thereby enhancing anti-tumor immunity independent of major histocompatibility complex class restriction. With expanding indications, their use is extending into older and less fit populations than those represented in pivotal trials, raising important questions regarding toxicity profiles in patients with greater comorbidity burden.</p><p><strong>Recent findings: </strong>Although cardiovascular toxicities of CAR T and bispecific T-cell engagers have been described, reported incidences are highly variable due to inconsistencies in adverse event definitions and surveillance across studies. Further, most studies have excluded patients with pre-existing heart failure or cardiomyopathy. Consequently, there is a lack of evidence-based guidance for risk stratification, peri-treatment management, or monitoring in this growing subgroup. Here, we briefly review the cardiovascular toxicities associated with T-cell redirecting therapies and highlight limitations in clinical trial inclusion criteria. We then emphasize the urgent need for uniformity in defining cardiovascular toxicities, as well as for dedicated studies in patients with pre-existing heart failure or cardiomyopathy as a distinct high-risk population.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Understanding of CHIP's Immunobiological Footprint with A Focus on Gastrointestinal Disorders: A Review of the Literature.","authors":"Kirti Arora, Rishi Chowdhary, Rachel McNulty, Rahul Chowdhary, Wesam Aleyadeh, Megh Patel, Abhay Singh","doi":"10.1007/s11912-026-01795-2","DOIUrl":"10.1007/s11912-026-01795-2","url":null,"abstract":"<p><strong>Purposeof review: </strong>Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the age-associated expansion of hematopoietic stem and progenitor cells (HSPCs) bearing somatic mutations in genes such as DNMT3A, TET2, ASXL1, and JAK2, without overt cytopenias or hematologic malignancy. CHIP is increasingly understood as a systemic inflammatory condition that influences extra-hematopoietic organs. Recent findings highlight its role in gastrointestinal (GI) pathology through immune dysregulation, chronic inflammation, and fibrogenic remodeling.</p><p><strong>Recent findings: </strong>In the liver, CHIP, particularly TET2 and DNMT3A mutations, enhances IL-6 and NLRP3 inflammasome signaling in Kupffer cells, promoting hepatic inflammation, fibrosis, and heightened risk for cirrhosis and hepatocellular carcinoma. In inflammatory bowel disease (IBD), persistent cytokine exposure may select for pro-inflammatory clones, with TET2-mutant CHIP linked to severe disease phenotypes. In colorectal cancer, mutant macrophage and monocyte populations derived from CHIP alter tumor immune microenvironments, affecting tumor progression and therapeutic responsiveness, including checkpoint blockade efficacy. Together, these findings suggest that hematopoietic clones harboring specific mutations may act as upstream regulators of chronic inflammation and carcinogenesis within the GI tract. This review consolidates gene-specific mechanisms, interactions with the gut-liver immune axis, and implications for targeted interventions linking CHIP with gastrointestinal inflammation, fibrosis, and malignancy.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13253656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of EZH2 ın Malıgnant Pleural Mesothelıoma and Beyond: Current Practıce and Future Perspectıves.","authors":"Mehmet Kucukoner, Tarik Demir, Abduljalil Mohammed Alsubaie, Ulas Alabalik, Aisha K Ibrahim, Mariaelena Pierobon, Lance Liotta","doi":"10.1007/s11912-026-01754-x","DOIUrl":"10.1007/s11912-026-01754-x","url":null,"abstract":"<p><strong>Purpose of review: </strong>Malignant pleural mesothelioma (MPM) remains a rare but highly aggressive malignancy with limited treatment options and poor prognosis. For nearly twenty years, platinum-pemetrexed chemotherapy has persisted as the unchanged standard treatment; although recent progress in immunotherapy has modestly disrupted this therapeutic plateau, survival outcomes remain disappointingly limited. This review aims to provide a comprehensive overview of the epigenetic landscape of MPM, focusing particularly on the oncogenic and therapeutic implications of enhancer of zeste homolog 2 (EZH2), and to discuss its potential as a target for novel therapeutic strategies and combination regimens.</p><p><strong>Recent findings: </strong>Epigenetic dysregulation has emerged as a central driver of mesothelioma pathogenesis. EZH2, the catalytic component of the polycomb repressive complex 2 (PRC2), mediates histone H3K27 trimethylation, silencing tumor suppressor genes and promoting malignant transformation. In addition to its canonical role, EZH2 has non-canonical oncogenic effects that modulate transcription, apoptosis, DNA repair, and immune evasion. High EZH2 expression correlates with BAP1 loss, which enhances chromatin remodeling defects and disease aggressiveness. Preclinical and early clinical data demonstrate that EZH2 inhibitors-including tazemetostat, valemetostat, GSK126, EPZ011989, tulmimetostat, and novel PROTAC-based degraders such as MS1943-can suppress tumor progression, modulate the tumor immune microenvironment, and restore therapeutic sensitivity. Furthermore, combination approaches integrating EZH2 inhibition with chemotherapy or immune checkpoint blockade show synergistic potential in overcoming resistance. EZH2 represents a pivotal epigenetic regulator and a promising therapeutic target in MPM. Further understanding the dual canonical and non-canonical roles of EZH2 in tumor biology will be key to optimizing targeted and combinatorial treatment strategies. Future research should focus on translating EZH2 inhibition into clinical benefit, identifying predictive biomarkers of response, and exploring rational combinations with chemotherapy, targeted drugs, or immunotherapy to improve survival outcomes in mesothelioma patients.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":"28 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13246576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}