Critical reviews in oncology/hematology最新文献

{"title":"Management of adverse events associated with TROP2-targeted antibody-drug conjugates in cancer patients","authors":"Zuer He ,&nbsp;Zijia Luo ,&nbsp;Peilin Dai ,&nbsp;Xiaoli Wang ,&nbsp;Jiqiao Yang","doi":"10.1016/j.critrevonc.2026.105153","DOIUrl":"10.1016/j.critrevonc.2026.105153","url":null,"abstract":"<div><div>Antibody-drug conjugates (ADCs) constitute an innovative category of anti-tumor therapeutics that selectively deliver cytotoxins to tumor cells, improving efficacy and reducing toxicity in comparison to systemic therapy. TROP2 serves as a significant target for ADCs in cancer detection and treatment. TROP2-targeted ADCs have shown promising efficacy in cancer therapy. However, it is essential to monitor expected adverse effects to ensure the anti-tumor efficacy and safety. This review clarifies the mechanisms and toxicological profiles of TROP2-targeted medicines based on clinical trials and recommendations, with the aim of providing solutions for the prevention, detection, and management of related adverse events.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105153"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055352","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":"Shaping immunotherapy through the tumor microenvironment: Translational perspectives","authors":"Vansh Vohra ,&nbsp;Meenakshi Dhanawat ,&nbsp;Rishabh Chalotra ,&nbsp;Bharat Bhushan ,&nbsp;Garima ,&nbsp;Jashan Girdhar ,&nbsp;Inamul Hasan Madar ,&nbsp;Randhir Singh ,&nbsp;Mohammad Fareed","doi":"10.1016/j.critrevonc.2026.105169","DOIUrl":"10.1016/j.critrevonc.2026.105169","url":null,"abstract":"<div><div>The tumour microenvironment (TME) is a simply orchestrator of cancer progression and a principal mediator of resistance to immunotherapy. This review explains the complex immunosuppressive ecosystem of the TME, highlighting mechanisms of immune evasion including the recruitment of regulatory T cells, myeloid-derived suppressor cells, and tumour-associated macrophages; metabolic competition via the Warburg effect and indoleamine 2,3-dioxygenase activity and hypoxia-driven upregulation of immune checkpoints such as PD-L1. We synthesize translational strategies designed to reprogram this hostile niche, moving beyond immune checkpoint inhibitor monotherapy. These approaches encompass metabolic targeting (e.g., MCT1/4, IDO inhibitors), stromal disruption (e.g., CAF inhibition, vascular normalization), and advanced cellular engineering, such as CAR-T cells resistant to exhaustion and cytokine-secreting constructs. We underline the synergy of combination therapies, integrating checkpoint blockade with chemotherapy, radiotherapy, oncolytic viruses, and adenosine pathway antagonists to augment immunogenic cell death and cytotoxic T lymphocyte infiltration. The predictive value of biomarkers including tumour mutational burden, microsatellite instability, and the spatial architecture of tumour-infiltrating lymphocytes is critically appraised. Furthermore, the review explores emerging frontiers such as neoantigen-based vaccines, microbiome modulation, and bispecific antibodies, underscoring their capacity to convert immunologically \"cold\" tumours into \"hot\", responsive lesions. By bridging preclinical insights with clinical trial evidence, this review speculates that the precise modulation of the TME is indispensable for unlocking durable, broad-spectrum antitumor immunity and defining the next generation of cancer immunotherapies.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105169"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109094","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":"The critical role of epithelial-mesenchymal transition (EMT) in colorectal cancer progression and therapeutic outcomes","authors":"Hailang Jiang,&nbsp;Bingtian Xu","doi":"10.1016/j.critrevonc.2026.105189","DOIUrl":"10.1016/j.critrevonc.2026.105189","url":null,"abstract":"<div><div>Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, driven largely by metastatic progression and therapeutic resistance. Despite advances in early detection and systemic treatment, a substantial proportion of patients develop disease that is refractory to conventional therapies. Epithelial-mesenchymal transition (EMT) is a dynamic and reversible cellular program that critically shapes CRC progression. Rather than functioning as a binary switch, EMT in CRC is increasingly understood as epithelial-mesenchymal plasticity (EMP), in which tumor cells occupy partial or hybrid epithelial/mesenchymal states. These intermediate phenotypes retain epithelial features while activating mesenchymal programs, enabling collective invasion, stem-like behavior, immune evasion, and resistance to therapy. This review provides a comprehensive analysis of the molecular drivers of EMT and EMP in CRC, including EMT-associated transcription factors (e.g., SNAIL, ZEB1), key signaling pathways (e.g., TGF-β, Wnt/β-catenin, Notch), and epigenetic regulators such as DNA methylation, histone modifications, and noncoding RNAs. The role of the tumor microenvironment, particularly cancer-associated fibroblasts and tumor-associated macrophages, in stabilizing hybrid EMT states through paracrine signaling and metabolic crosstalk is examined in detail. Importantly, EMP and hybrid EMT states are highlighted as central contributors to resistance across chemotherapy, targeted therapy, radiotherapy, and immunotherapy, driven by phenotypic flexibility rather than irreversible mesenchymal conversion. Emerging therapeutic strategies targeting EMT-associated signaling, epigenetic plasticity, and EMT-immune interactions are discussed, alongside the potential of liquid biopsy approaches to dynamically monitor EMT states during treatment. A refined understanding of epithelial–mesenchymal plasticity and hybrid EMT states is essential for the development of rational combination therapies and biomarker-guided strategies aimed at overcoming therapeutic resistance and limiting metastatic progression in colorectal cancer.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105189"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146151450","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":"Digital twins in oncology: From predictive modelling to personalised treatment strategies","authors":"David B. Olawade ,&nbsp;Emmanuel O. Oisakede ,&nbsp;Oluwakemi Jumoke Bello ,&nbsp;Claret Chinenyenwa Analikwu ,&nbsp;Eghosasere Egbon ,&nbsp;Adeyinka Ojo","doi":"10.1016/j.critrevonc.2026.105171","DOIUrl":"10.1016/j.critrevonc.2026.105171","url":null,"abstract":"<div><div>The digital twin (DT) concept, originating from engineering disciplines, has emerged as a transformative technology in healthcare, particularly in oncology. A digital twin creates a dynamic, virtual replica of a patient's physiological and pathological state, integrating multi-dimensional data to enable personalised cancer care. Despite growing interest, comprehensive reviews examining the breadth of DT applications in oncology remain limited. This narrative review aims to synthesise current evidence on digital twin applications in oncology, evaluate their potential to transform cancer care delivery, and identify challenges hindering clinical translation. A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and IEEE Xplore databases from inception to September 2025. Studies describing DT development, validation, or application in any cancer type were included. Grey literature, conference proceedings, and expert commentaries were also reviewed to capture emerging trends. Digital twins demonstrate applications across the cancer care continuum, including precision treatment selection, radiotherapy optimisation, drug development, immuno-oncology modelling, surgical planning, and survivorship care. Integration of multi-omics data, imaging biomarkers, and artificial intelligence enables dynamic simulation of tumour behaviour and treatment response. However, challenges persist in data integration, model validation, computational scalability, and ethical governance. Digital twin technology holds substantial promise for advancing precision oncology through predictive, personalised, and adaptive care strategies. Addressing current limitations through interdisciplinary collaboration and regulatory framework development is essential for clinical implementation.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105171"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099949","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":"Research training in radiation oncology: a scoping review of global pathways, barriers and enablers","authors":"Joanna Kucharczak ,&nbsp;Anushka Irodi ,&nbsp;Katie Spencer ,&nbsp;Gerard M. Walls ,&nbsp;Christopher M. Jones","doi":"10.1016/j.critrevonc.2026.105162","DOIUrl":"10.1016/j.critrevonc.2026.105162","url":null,"abstract":"<div><h3>Background</h3><div>There is a disparity between the importance of radiation oncology (RO) to cancer care and the research activity that underpins it. This may relate to inadequate availability of, or barriers within, residency research training. This scoping review sought to characterize the barriers and enablers to RO research training, and to summarize relevant training pathways.</div></div><div><h3>Methods</h3><div>Systematic Medline and Embase searches were conducted using “RO”, “research”, “training”, and related terms, to identify reports published between 2010 and 2025. Manuscripts were screened using predefined inclusion and exclusion criteria to select those describing research initiatives, and barriers and enablers to resident-level research. These features were extracted along with country of origin and study design parameters.</div></div><div><h3>Results</h3><div>Of 1745 identified manuscripts, 54 were included. Most reports originated from North America (n = 24/54; 44.4 %), Europe (n = 12/54; 22.2 %) and Australasia (n = 8/54; 14.8 %). A majority were survey-based studies (n = 27/54; 50.0 %) or observational cohort analyses (n = 10/54; 18.5 %). We identified seven countries with mandated resident-level research training and three regions/countries with RO-specific physician scientist training programs. These varied from integrated training schemes that include higher research degree completion, to short-interval initiatives. Five programs were supported by metrics detailing their impact. Reported enablers and barriers demonstrated a subtle geographic variation but included protected time and funding, mentorship and attainment of research skills.</div></div><div><h3>Conclusion</h3><div>There is global variation in research training during RO residency but numerous shared enablers and barriers. These data provide shared best practice and a scaffold on which national and international societies can build improved research training pathways to redress the radiation research deficit.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105162"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097748","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":"Ubiquitin regulatory code: unraveling tumor cell ferroptosis","authors":"Xinjing Liu ,&nbsp;Jian Liu ,&nbsp;Wenqing Chen ,&nbsp;Jimei Zhang ,&nbsp;Yiju Wei ,&nbsp;Lili Sun","doi":"10.1016/j.critrevonc.2026.105172","DOIUrl":"10.1016/j.critrevonc.2026.105172","url":null,"abstract":"<div><div>Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation, characterized by the inhibition of glutathione peroxidase 4 (GPX4), glutathione (GSH) depletion, and peroxidation of polyunsaturated fatty acids (PUFAs). Due to metabolic reprogramming and impaired antioxidant defenses, tumor cells exhibit heightened sensitivity to ferroptosis, positioning it as a promising therapeutic target for cancer. Within the cellular protein regulatory network, post-translational modifications (PTMs) —particularly ubiquitination and ubiquitin-like modifications (Ubls, including SUMOylation, NEDDylation, UFMylation, and ATG8ylation) —serve as molecular switches by modulating the stability of key proteins such as GPX4 and SLC7A11. This review systematically dissects how E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) orchestrate redox homeostasis and iron metabolism, through site-specific ubiquitination of critical proteins. Furthermore, we highlight the development of small-molecule inhibitors targeting these modifications, emphasizing their potential to disrupt ferroptosis resistance pathways. By integrating mechanistic insights with therapeutic applications, this study not only elucidates the dynamic complexity of ubiquitin-mediated regulatory networks but also proposes innovative strategies leveraging Ub/Ubl modifications for targeted cancer therapy. These findings provide a foundational theoretical framework and actionable research directions for advancing precision medicine in oncology.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105172"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133835","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":"Optimizing bridging radiotherapy prior to CAR-T cell therapy: An evidence-based approach","authors":"Pierre Loap ,&nbsp;Clémentine Sarkozy ,&nbsp;Remi Dendale ,&nbsp;Youlia Kirova","doi":"10.1016/j.critrevonc.2026.105181","DOIUrl":"10.1016/j.critrevonc.2026.105181","url":null,"abstract":"<div><div>Bridging radiotherapy has emerged as a valuable strategy to ensure optimal conditions for chimeric antigen receptor T-cell (CAR-T) therapy in relapsed or refractory hematologic malignancies. By controlling disease burden and maintaining clinical stability in the interval between leukapheresis and CAR-T infusion, it helps counteract the risk of tumor progression that can diminish treatment efficacy. Evidence from diffuse large B-cell lymphoma (DLBCL) and other lymphomas supports the use of hypofractionated radiotherapy to achieve rapid local control with minimal delays, while preliminary data in multiple myeloma expand its applicability. Radiotherapy’s immunomodulatory effects, including enhanced antigen presentation and inflammation, may bolster CAR-T cell activity, though careful consideration is required to avoid potential immunosuppressive consequences. The optimal integration of bridging radiotherapy encompasses timing after leukapheresis, rapid planning and delivery, judicious choice of fractionation, and close coordination between hematology and radiotherapy teams. Tailoring dose and technique further refines the therapeutic window, minimizing toxicity while maintaining efficacy. These evidence-based practice propositions provide a comprehensive framework for implementing bridging radiotherapy. By outlining indications, workflow, fractionation schemes, and technical approaches, these guidelines facilitate the seamless incorporation of radiotherapy into CAR-T therapy protocols, ultimately aiming to improve patient outcomes through enhanced disease control and synergistic antitumor immunity.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105181"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133819","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":"Anti-EGFR rechallenge compared with standard of care for patients with ctDNA RAS/BRAF wild-type chemorefractory metastatic colorectal cancer: A systematic review and meta-analysis","authors":"Olesya Kuznetsova ,&nbsp;Elena Battaiotto ,&nbsp;Giulia Malvezzi ,&nbsp;Lorenzo Gervaso ,&nbsp;Maria Giulia Zampino ,&nbsp;Chiara Alessandra Cella ,&nbsp;Lavinia Benini ,&nbsp;Francesca Spada ,&nbsp;Mikhail Fedyanin ,&nbsp;Alexey Tryakin ,&nbsp;Fabio Carbone ,&nbsp;Brigida Anna Maiorano ,&nbsp;Davide Ciardiello ,&nbsp;Nicola Fazio","doi":"10.1016/j.critrevonc.2026.105180","DOIUrl":"10.1016/j.critrevonc.2026.105180","url":null,"abstract":"<div><div>Anti-EGFR rechallenge emerged as a potential therapeutic option for patients with chemorefractory metastatic colorectal cancer (mCRC) that maintained a circulating tumor DNA (ctDNA) <em>RAS/BRAF</em> wild type (WT) status. However, its efficacy compared to standard of care (SoC) in randomized controlled trials (RCTs) remains uncertain. In our systematic review and meta-analysis, we investigated the outcomes of anti-EGFR rechallenge versus SoC for patients with pretreated ctDNA <em>RAS/BRAF</em> WT mCRC. This study followed the PRISMA guidelines, and a systematic search of PubMed and ASCO/ESMO meeting abstracts was conducted in October 2025 for relevant RCTs. Pooled odds ratios (OR) for disease control rate (DCR) and objective response rate (ORR), and hazard ratios (HR) for survival outcomes were calculated. We identified three phase II randomized trials with 320 patients. Anti-EGFR rechallenge significantly improved DCR (OR = 3.39, 95 % CI 2.13–5.39), ORR (OR = 5.13, 95 % CI 2.30–11.41) and progression free survival (HR 0.674; 95 % CI, 0.499–0.909; p = 0.009) compared to SoC. No overall survival benefit was detected (HR 0.895; 95 % CI 0.736–1.087; p = 0.263). These findings support the use of anti-EGFR rechallenge strategy aslater-line treatment when tumor shrinkage is a clinical priority. Further evidence from prospective trials is required.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105180"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133851","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":"Real-world evidence for 10 oncology drugs approved in the last 5 years: A comprehensive narrative synthesis","authors":"Fausto Petrelli ,&nbsp;Lara Colombo Zefinetti ,&nbsp;Maria Chiara Parati ,&nbsp;Mara Ghilardi ,&nbsp;Karen Borgonovo ,&nbsp;Lorenzo Dottorini ,&nbsp;Mauro Rossitto ,&nbsp;Giuseppina Dognini ,&nbsp;Daniela Petrò ,&nbsp;Elena Balconi ,&nbsp;Emanuela Oggionni ,&nbsp;Emanuela Castelli ,&nbsp;Alberto Zambelli","doi":"10.1016/j.critrevonc.2026.105178","DOIUrl":"10.1016/j.critrevonc.2026.105178","url":null,"abstract":"<div><h3>Importance</h3><div>Randomized controlled trials (RCTs) establish the efficacy of new oncology drugs but often exclude older adults, patients with comorbidities, and individuals with poorer performance status. Real-world evidence (RWE) is therefore essential to determine whether trial benefits translate to the broader populations treated in routine practice.</div></div><div><h3>Objective</h3><div>To synthesize contemporary RWE on the effectiveness and safety of ten oncology drugs approved between 2020 and 2025 for solid tumors, focusing on studies with ≥ 100 patients to maximize robustness and generalizability.</div></div><div><h3>Evidence review</h3><div>A systematic search of PubMed/MEDLINE, Embase, Scopus, Web of Science, and major conference proceedings (ASCO, ESMO, AACR) identified observational cohorts, registries, expanded-access programs, and claims-based studies published from January 2020 to January 2025.</div></div><div><h3>Findings</h3><div>Twenty studies (N &gt; 3400) met inclusion criteria: breast cancer (9), lung cancer (7), urothelial carcinoma (3), and endometrial cancer (1). In breast cancer, sacituzumab govitecan reproduced ASCENT outcomes (ORR 27–30 %; PFS 4.8–5.2 months), trastuzumab deruxtecan achieved ORRs near 70 % in HER2-positive disease and median PFS 7.5 months in HER2-low cohorts, and elacestrant showed real-world time-to-next-treatment of 7.9–10.8 months in ESR1-mutant ER+ /HER2 − disease. In NSCLC, sotorasib and adagrasib demonstrated ORRs of ∼28–34 % and PFS 3.5–6 months, selpercatinib provided durable disease control, and MET inhibitors (capmatinib, tepotinib) yielded PFS around 6–7 months. In urothelial carcinoma, enfortumab vedotin produced ORRs of 31–73 % across datasets. In endometrial cancer, dostarlimab generated highly durable responses in dMMR/MSI-H disease.</div></div><div><h3>Conclusions</h3><div>RWE confirms the effectiveness and safety of multiple recently approved oncology drugs reinforcing the external validity of RCTs.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105178"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138233","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":"Adjuvant aspirin and Cyclooxygenase-2 inhibitors in resected, PIK3CA-mutated colorectal cancer: A systematic review and meta-analysis of randomized controlled trials","authors":"Ellen R. Blanchard-Cavagis ,&nbsp;Pedro C. Abrahão Reis ,&nbsp;Filipe Luis Vasconcelos Visani ,&nbsp;Heloísa Carneiro Brito ,&nbsp;Isabela C. Diniz ,&nbsp;Caio Dabbous de Liz","doi":"10.1016/j.critrevonc.2026.105167","DOIUrl":"10.1016/j.critrevonc.2026.105167","url":null,"abstract":"<div><h3>Background</h3><div>Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are widely available and inexpensive agents with proposed antitumor activity, particularly in tumors harboring <em>PIK3CA</em> mutations. This meta-analysis of randomized controlled trials (RCTs) evaluated whether adjuvant NSAID therapy improves outcomes in patients with resected <em>PIK3CA</em>-mutated colorectal cancer (CRC).</div></div><div><h3>Methods</h3><div>PubMed, Embase, and the Cochrane Library were systematically searched for RCTs assessing NSAID use following curative-intent resection of CRC in patients with confirmed <em>PIK3CA</em> mutations. Pooled hazard ratios (HRs) with corresponding 95 % confidence intervals (CIs) were calculated for disease-free survival (DFS) and overall survival (OS) using both fixed and random-effects models. Sensitivity analyses excluded participants with low-dose aspirin exposure concomitant with cyclooxygenase-2 (COX-2) inhibitors.</div></div><div><h3>Results</h3><div>Among 477 records screened, four RCTs met eligibility criteria, comprising 426 patients assigned to NSAIDs (aspirin or COX-2 inhibitors) and 363 receiving placebo. Adjuvant NSAID therapy improves DFS (HR 0.65; 95 % CI, 0.46–0.90). In sensitivity analyses excluding concomitant aspirin exposure, a similar magnitude of effect was observed (HR 0.57; 95 % CI, 0.39–0.83). The pooled OS analysis was not statistically significant (HR 0.78; 95 % CI, 0.39–1.57). Exclusion of low-dose aspirin users was associated with lower mortality risk (HR 0.54; 95 % CI, 0.30–0.99), although these findings should be interpreted cautiously.</div></div><div><h3>Conclusion</h3><div>Adjuvant NSAID therapy is associated with improved DFS in patients with <em>PIK3CA</em>-mutated CRC. OS benefit remains uncertain, and findings from sensitivity analyses are exploratory. These findings support consideration of NSAIDs as a biomarker-informed adjuvant strategy in selected patients while underscoring the need for confirmatory evidence from ongoing randomized trials.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105167"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101251","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}