Critical reviews in oncology/hematology最新文献

{"title":"Molecular insights into the role of tumor-specific endothelial cells in metastasis","authors":"Tahereh Zarei Taher ,&nbsp;Amir Hossein Kheirkhah ,&nbsp;Sara Mehri ,&nbsp;Omid Mahmoudian ,&nbsp;Sajjad Atashi ,&nbsp;Maria Kavianpour","doi":"10.1016/j.critrevonc.2025.104964","DOIUrl":"10.1016/j.critrevonc.2025.104964","url":null,"abstract":"<div><div>Tumor-specific endothelial cells (TECs) play a crucial role in tumor advancement, metastasis, and immune evasion, distinguishing themselves from normal endothelial cells (NECs) through unique gene expression and enhanced pro-angiogenic signaling. TECs facilitate metastasis by increasing vascular permeability and supporting tumor angiogenesis, while also aiding immune evasion via the expression of checkpoint molecules, such as PD-L1, which dampen T cell activity. Targeting TECs shows promise for improving cancer therapy. Anti-angiogenic treatments, including VEGF inhibitors like bevacizumab, aim to reduce tumor vascularity. Still, TECs can develop resistance through alternative signaling pathways, necessitating combination therapies that involve agents targeting FGF and PDGF. Immune checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 antibodies, can enhance immune responses when combined with anti-angiogenic treatments. Furthermore, targeting TEC-related pathways, such as TGF-β and Angiopoietin-2, may stabilize tumor vasculature and limit metastasis. Given the heterogeneity of TECs, multi-targeted approaches integrating anti-angiogenic and immune-modulating therapies are crucial. Advances in single-cell transcriptomics and proteomics will refine TEC-targeted treatments, supporting precision medicine in oncology. This review highlights the therapeutic potential of TECs and explores innovative strategies for enhancing cancer treatment outcomes.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"216 ","pages":"Article 104964"},"PeriodicalIF":5.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182416","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":"Protein post-translational modifications in CAR-T cells: Novel strategies to amplify antitumor efficacy via epigenetic and metabolic circuitry","authors":"Jiayi Li ,&nbsp;Huihui Sun ,&nbsp;Wenying Li ,&nbsp;Ningning Zhao ,&nbsp;Zhigang Guo ,&nbsp;Jiannan Chen ,&nbsp;Jun Yu","doi":"10.1016/j.critrevonc.2025.104968","DOIUrl":"10.1016/j.critrevonc.2025.104968","url":null,"abstract":"<div><div>Chimeric Antigen Receptor T cell (CAR-T) therapy has revolutionized cancer treatment, achieving remarkable success in hematological malignancies. However, its efficacy against solid tumors remains limited, primarily due to challenges such as the immunosuppressive tumor microenvironment (TME) and T cell exhaustion. Protein post-translational modifications (PTMs), including phosphorylation, ubiquitination, glycosylation, acetylation, and lactylation, are pivotal in regulating T cell signaling, activation, persistence, and metabolic adaptation, thereby offering novel opportunities to enhance CAR-T therapy. The impact of PTMs on CAR-T cell functionality is systematically explored in this review, with a particular emphasis on their regulatory roles in key processes such as T cell activation, immune checkpoint modulation, and metabolic reprogramming. Specifically, phosphorylation is crucial in governing T cell activation and exhaustion; ubiquitination is involved in modulating immune checkpoint stability; glycosylation impacts immune synapse formation; and acetylation and lactylation are key in shaping metabolic adaptations crucial for sustained CAR-T efficacy. By leveraging PTM-targeted strategies—including kinase inhibitors, deubiquitinase modulators, and metabolic pathway interventions—CAR-T therapy can be optimized to overcome its current limitations. This review highlights the transformative potential of PTM-based approaches in advancing precision cancer immunotherapy and provides a theoretical foundation for future research and therapeutic innovation.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"216 ","pages":"Article 104968"},"PeriodicalIF":5.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156589","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":"Guidelines for the prevention and diagnosis of vaginal and vulvar cancers: A systematic review","authors":"Ambika Aul,&nbsp;Susan Jordan,&nbsp;Tracey DiSipio","doi":"10.1016/j.critrevonc.2025.104970","DOIUrl":"10.1016/j.critrevonc.2025.104970","url":null,"abstract":"<div><h3>Background</h3><div>Variation in care is known to exist for those diagnosed with vaginal and vulvar cancers. Guidelines are integral to providing a consistent, quality standard of care. To provide an evidence-based background for vaginal and vulvar cancers, a systematic review was conducted to identify available guidelines relevant to prevention and early detection; presentation, initial investigations and referral; and diagnosis.</div></div><div><h3>Methods</h3><div>We conducted a systematic search of databases (CINAHL, Cochrane Library, Embase, PubMed, Scopus, Web of Science) and targeted websites (n = 23) to identify guidelines published in English within the past 10 years (from 2013 onwards) relevant to either vaginal or vulvar cancers and pertaining to the first three steps of the cancer care continuum. We screened the guidelines, extracted recommendations and statements, and assessed their quality using standard forms.</div></div><div><h3>Results</h3><div>A total of 45 guidelines were included in this review (33 evidence-based, 12 consensus-based). Guidelines were developed by a range of professional organisations and across countries. Guidelines covered multiple topics including prevention and early detection (n = 37; 82 %), presentation, initial investigations and referral (n = 24; 53 %), and diagnosis (n = 23; 51 %). Common and consistent guideline recommendations and statements were identified. Example recommendation topics included risk factors, management of precursor conditions, signs and symptoms, initial tests and referral, and diagnostic workup. Few timeframes were specified.</div></div><div><h3>Conclusion</h3><div>This review has collated relevant and current guidelines available to health professionals from prevention to diagnosis of vaginal and vulvar cancers. Our synthesis demonstrates consistency but a lack of specificity in the available recommendations/statements.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"216 ","pages":"Article 104970"},"PeriodicalIF":5.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152309","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":"Breaking barriers in CRC immunotherapy: Cutting-edge advances in personalized peptide vaccine development","authors":"Hairuo Huang ,&nbsp;Jianmin Ren ,&nbsp;Deming Jiang ,&nbsp;Shurong Hu ,&nbsp;Qiao Yu ,&nbsp;Bufu Tang ,&nbsp;Pingbo Xu ,&nbsp;Jingwen Liu","doi":"10.1016/j.critrevonc.2025.104967","DOIUrl":"10.1016/j.critrevonc.2025.104967","url":null,"abstract":"<div><div>Globally, Colorectal carcinoma (CRC) ranking second among malignancies in terms of fatality rate. Despite recent advancements in CRC immunotherapy, The therapeutic effectiveness of existing treatments remains limited attributable to the strongly immune-inhibitory milieu within CRC tumors.The development of groundbreaking therapies remains an urgent priority.As an innovative immunotherapeutic approach, antigenic peptide vaccines are increasingly studied for their potential to activate the immune system for targeted tumor cell elimination, along with advantages such as high safety and ease of production. Among these, personalized peptide vaccines (PPVs), tailored based on patient MHC-1 haplotypes and pre-vaccination immune status, have demonstrated remarkable potential in CRC treatment, particularly for microsatellite instability-high (MSI-H) subtypes.This review summarizes recent advances and key technologies in tumor peptide vaccine development, highlighting their emerging role in CRC treatment paradigms.It also examines the technological evolution from universal to individualized vaccine design. Furthermore, we delve into the influence of the immune microenvironment on vaccine efficacy and propose novel strategies for targeting immune modulation to suppress tumor metastasis.We highlight the latest preclinical and clinical findings, including advancements in novel adjuvants, neoantigen screening, nanodelivery systems, and combination therapies. Finally, we outline future research priorities and challenges in this field.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"216 ","pages":"Article 104967"},"PeriodicalIF":5.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152254","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":"Extended molecular profiling in mesenchymal tumors: a consensus paper from the Italian Sarcoma Group","authors":"Lorenzo D’Ambrosio ,&nbsp;Marta Sbaraglia ,&nbsp;Alessandra Merlini ,&nbsp;Martina Rabino ,&nbsp;Giovanni Grignani ,&nbsp;Viviana Appolloni ,&nbsp;Giuseppe Badalamenti ,&nbsp;Giacomo Giulio Baldi ,&nbsp;Elena Bellan ,&nbsp;Matteo Benelli ,&nbsp;Alexia Francesca Bertuzzi ,&nbsp;Roberto Biagini ,&nbsp;Giuseppe Bianchi ,&nbsp;Antonella Boglione ,&nbsp;Antonella Brunello ,&nbsp;Domenico Andrea Campanacci ,&nbsp;Ferdinando Cananzi ,&nbsp;Paolo Giovanni Casali ,&nbsp;Beatrice Casini ,&nbsp;Marilena Cesari ,&nbsp;Silvia Stacchiotti","doi":"10.1016/j.critrevonc.2025.104960","DOIUrl":"10.1016/j.critrevonc.2025.104960","url":null,"abstract":"<div><div>Extended molecular profiling using massive parallel sequencing (MPS) technologies, commonly referred to as next-generation sequencing (NGS), has revolutionized cancer diagnosis and treatment, including in bone and soft tissue sarcomas (BSTS). This heterogeneous group of mesenchymal tumors presents a complex spectrum of genetic alterations, such as chromosomal rearrangements, point mutations, and copy number variations. Unlike carcinomas, where driver mutations are often well defined, the role of specific genomic signatures in dictating BSTS prognosis and therapy response remains to be fully elucidated. Despite its promise, the adoption of MPS/NGS in BSTS is limited by variability in testing access, turnaround times, specimen quality, costs, and data interpretation. Although identified alterations are often not yet directly targetable, they provide critical insights that can refine diagnosis, enable better patient stratification, and guide treatment strategies. To optimize the use of MPS/NGS in BSTS, harmonization and multidisciplinary collaboration within molecular tumor boards (MTBs) are essential. With this aim, the Italian Sarcoma Group ETS (ISG) convened a consensus meeting to establish best practices for integrating MPS/NGS into everyday clinical care. ISG experts developed ten consensus statements: the first five address the role of extended molecular profiling in BSTS diagnostics, while the others offer guidance on MPS/NGS use and interpretation when searching for potentially actionable targets in the treatment of advanced disease. Furthermore, collaboration with the National Rare Cancer Network to offer expert consultation and systematically correlate MPS/NGS findings with clinical outcomes for BSTS cases undergoing extended molecular profiling will be critical to advancing precision medicine in this field.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"216 ","pages":"Article 104960"},"PeriodicalIF":5.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152267","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":"Artificial intelligence enabled tumor diagnosis and treatment: Status, breakthroughs and challenges","authors":"Yani Hu ,&nbsp;Shuai Liang ,&nbsp;Xu Zhou ,&nbsp;Zhipeng Zeng ,&nbsp;Junli Ding ,&nbsp;Dong Hua","doi":"10.1016/j.critrevonc.2025.104963","DOIUrl":"10.1016/j.critrevonc.2025.104963","url":null,"abstract":"<div><div>In recent years, cancer has emerged as a leading threat to global health, underscoring the critical need for early detection, precise diagnosis, and effective treatment to enhance patient outcomes. Against this backdrop, the rapid adoption of artificial intelligence (AI) in oncology has been driven by three key factors: the proliferation of large-scale datasets, breakthroughs in computational hardware and algorithms, and the development of innovative deep learning (DL) architectures. Specifically, AI applications now span the entire oncology workflow, including image-based screening, pathological diagnosis, intelligent decision support, treatment outcome prediction, and personalized therapy design. Hence, we aim to synthesize the recent explosive growth in AI applications across the oncology continuum and to critically examine the translational challenges that hinder clinical deployment. More importantly, this article provides a timely update on cutting-edge advancements (e.g., multimodal learning, explainable AI and AI-driven drug discovery) and offers a forward-looking perspective on future directions, consolidating actionable insights for researchers and clinicians and paving the way for next-generation AI-driven precision oncology.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"216 ","pages":"Article 104963"},"PeriodicalIF":5.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139366","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":"Dynamic crosstalk between tumor-associated macrophages and cancer-associated fibroblasts in pancreatic ductal adenocarcinoma","authors":"Jinping Zhang ,&nbsp;Dandan Zhang ,&nbsp;Xun Liu ,&nbsp;Mengdie Xu ,&nbsp;Jinwei He ,&nbsp;Jing Ma ,&nbsp;Zhihui Yang","doi":"10.1016/j.critrevonc.2025.104965","DOIUrl":"10.1016/j.critrevonc.2025.104965","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely poor prognosis, with current therapeutic approaches demonstrating suboptimal efficacy. The development of novel treatment strategies or combination therapies to improve clinical outcomes is therefore imperative. Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) serve as pivotal regulators in PDAC progression. These cell populations establish a positive feedback loop through both direct and indirect interactions, contributing significantly to stromal desmoplasia, the formation of a tumor immunosuppressive microenvironment (TIME), and the development of treatment resistance. The underlying interaction mechanisms may offer promising therapeutic targets for PDAC patients. This review presents the first comprehensive summary of the bidirectional interaction mechanisms between TAMs and CAFs in PDAC. Building upon existing research, we comprehensively elucidate recent advances in understanding these mechanisms and discuss emerging therapeutic strategies targeting these interactions. Furthermore, we propose anticipated future research directions, aiming to provide novel insights into PDAC progression and identify potential therapeutic avenues.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"216 ","pages":"Article 104965"},"PeriodicalIF":5.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139387","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":"Impact of exercise in patients with pancreatic cancer across different treatment phases: A systematic review","authors":"Linda Toniolo ,&nbsp;Anita Borsati ,&nbsp;Cristina Crespo-Garcia ,&nbsp;Diana Giannarelli ,&nbsp;Christian Ciurnelli ,&nbsp;Gloria Adamoli ,&nbsp;Lorenzo Belluomini ,&nbsp;Ilaria Trestini ,&nbsp;Daniela Tregnago ,&nbsp;Federico Schena ,&nbsp;Robert U. Newton ,&nbsp;Salvatore Paiella ,&nbsp;Roberto Salvia ,&nbsp;Michele Milella ,&nbsp;Sara Pilotto ,&nbsp;Alice Avancini","doi":"10.1016/j.critrevonc.2025.104961","DOIUrl":"10.1016/j.critrevonc.2025.104961","url":null,"abstract":"<div><h3>Background</h3><div>With a dismal prognosis of 8–10 % 5-year survival since diagnosis, pancreatic cancer remains one of the most aggressive oncological diseases. This work aimed to evaluate the effects of exercise medicine on safety and feasibility, physical fitness, body composition, patient-reported outcomes, and clinical outcomes across different treatment phases in patients with pancreatic cancer.</div></div><div><h3>Method</h3><div>PubMed, Cochrane, and Scopus databases were systematically screened to identify single-arm studies and randomized/non-randomized controlled trials investigating a physical exercise intervention in patients with pancreatic cancer. The RoB 2 and ROBINS-I tools were used to evaluate study quality for randomized and non-randomized studies, respectively. Qualitative and quantitative synthesis approaches were used.</div></div><div><h3>Results</h3><div>Among the 5550 identified records, 11 randomized controlled trials and 6 non-randomized studies were considered eligible. Five investigations were conducted in the neoadjuvant setting, eight in the rehabilitative and three during palliative phases. Regarding neoadjuvant exercise, there were no significant changes in cardiorespiratory fitness and muscle strength, whilst a gain in muscle mass was detected. Similarly, in the rehabilitative setting, mixed results were observed for cardiorespiratory fitness and body composition; a positive impact was registered in strength, glucose levels, tryptophan metabolism, and quality of life after 3 months of intervention. In the palliative setting, significant improvements were observed for muscle strength and quality of life, but not for clinical outcomes. <strong>Conclusion:</strong> Although physical exercise may ameliorate sequelae of pancreatic cancer, further investigation is necessary to understand the real impact of exercise medicine interventions in this population and across different treatment phases.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"216 ","pages":"Article 104961"},"PeriodicalIF":5.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126612","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":"Comprehensive analysis of BRCA1/2 mutations, “BRCAness” and PARP inhibitors in melanoma","authors":"Dimitrios Stylianakis ,&nbsp;Ioannis Stylianakis ,&nbsp;Haris Annette Benjamin ,&nbsp;Serafina Martella ,&nbsp;Andreas Tziotis ,&nbsp;Benedetta Pellegrino ,&nbsp;Pushpamali De Silva ,&nbsp;Marios Giannakis ,&nbsp;Fabiana Perrone ,&nbsp;Matteo Lambertini ,&nbsp;Cinzia Solinas ,&nbsp;Nerina Denaro","doi":"10.1016/j.critrevonc.2025.104962","DOIUrl":"10.1016/j.critrevonc.2025.104962","url":null,"abstract":"<div><div>The BRCA1 and BRCA2 genes encode critical proteins in the homologous recombination (HR) DNA repair pathway. While their role in hereditary breast and ovarian cancer syndromes is well established, recent evidence suggests a more nuanced role in other malignancies, including melanoma, where homologous recombination deficiency (HRD) occurs in 18–57 % of cases. This review is the first to comprehensively synthesize current findings on epidemiology and molecular mechanisms, while investigating potential predictive biomarkers, diagnostic implications, and therapeutic relevance of BRCA1/2 mutations in melanoma. We conducted an in-depth analysis of risk ratio (RR) in individuals with BRCA1 and BRCA2 mutations separately, across both traditionally linked cancers and various skin cancer types. Particular focus was given to melanoma, critically evaluating conflicting evidence suggesting a risk ratio ranging from 1.44 to 3.31, with variation between BRCA1 and BRCA2 carriers. Importantly, we explore the concept of \"BRCAness\" in melanoma—the phenotypic state where tumors display HR repair defects similar to BRCA-mutant cancers despite lacking BRCA1/2 alterations—alongside its predictive and therapeutic value. We assess the clinical promise of PARP inhibitors in common melanoma subtypes, both as monotherapy and combined with immunotherapy, alkylating agents, and MAPK-targeting agents. Resistance mechanisms, hematologic and gastrointestinal toxicities, and financial disparities are discussed as barriers to sustained treatment. Understanding the intersection of homologous recombination dysfunction and melanoma biology may refine diagnostic stratification, enhance prognostic accuracy, and enable rational integration of PARP inhibitors and targeted therapies into future treatment paradigms for melanoma patients.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"215 ","pages":"Article 104962"},"PeriodicalIF":5.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117861","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":"Targeted doublet therapy with encorafenib and cetuximab for BRAF V600E-mutant metastatic colorectal cancer: A systematic review and meta-analysis","authors":"Muhammad Ansab ,&nbsp;Shree Rath ,&nbsp;Eiman Araib ,&nbsp;Ghazal Ishaque ,&nbsp;Noor Ul Huda Ramzan ,&nbsp;Soban Ali Qasim ,&nbsp;Ibrahim Halil Sahin","doi":"10.1016/j.critrevonc.2025.104947","DOIUrl":"10.1016/j.critrevonc.2025.104947","url":null,"abstract":"<div><h3>Background</h3><div><em>BRAF</em> V600E-mutated metastatic colorectal cancer (mCRC) represents a biologically aggressive subset with poor prognosis and limited response to conventional therapies. While dual inhibition of BRAF and EGFR with encorafenib and cetuximab has emerged as a promising therapeutic strategy, a comprehensive quantitative synthesis of its efficacy and safety has been lacking.</div></div><div><h3>Methods</h3><div>We conducted a systematic review and meta-analysis of studies evaluating the efficacy and safety of encorafenib combined with cetuximab in <em>BRAF</em> V600E-mutated mCRC. Nine studies were included: three randomized trials, one non-randomized early-phase interventional study, and five real-world cohort studies. Data were extracted from randomized controlled trials and cohort studies. A random-effects model was used to pool survival data through reconstructed KM-curves data, treatment response rates, and adverse events. Heterogeneity and publication bias were assessed using I² statistics, Baujat plots, and LFK indices.</div></div><div><h3>Results</h3><div>This study included 1063 patients from 9 studies. The pooled mean overall survival was 8.7 months (95 % CI: 6.7–12.0), with OS rates at 6, 12, and 18 months of 65 %, 35 %, and 18 %, respectively. Median progression-free survival was 3.7 months (95 % CI: 2.8–4.6). The pooled objective response rate was 25 % (95 % CI: 22–30 %), while partial and complete response rates were 22 % and 2 %, respectively. Disease control was achieved in 67 % of patients (95 % CI: 58–76 %), and 30 % experienced grade ≥ 3 adverse events.</div></div><div><h3>Conclusions</h3><div>This meta-analysis supports the use of encorafenib plus cetuximab as an effective and tolerable regimen in patients with <em>BRAF</em> V600E-mutated mCRC, offering modest improvements in survival and disease control. Future trials should prioritize biomarker-guided treatment, explore triplet and first-line combinations, and address mechanisms of resistance to enhance durable clinical benefit.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"216 ","pages":"Article 104947"},"PeriodicalIF":5.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115489","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}