Critical reviews in oncology/hematology最新文献

{"title":"Immunotherapy in locally advanced head and neck squamous cell carcinoma: The current status and future outlook","authors":"Bahadır Köylü ,&nbsp;Fatih Selçukbiricik ,&nbsp;Sercan Aksoy ,&nbsp;Deniz Can Güven","doi":"10.1016/j.critrevonc.2026.105145","DOIUrl":"10.1016/j.critrevonc.2026.105145","url":null,"abstract":"<div><div>Head and neck squamous cell carcinoma presents a significant global health burden, with the majority of cases diagnosed at a locally advanced stage requiring multimodal therapy. While the immune checkpoint inhibitors have transformed outcomes in the recurrent/metastatic setting, their role in locally advanced head and neck squamous cell carcinoma is still evolving. In resectable disease, two recent phase III trials (KEYNOTE-689 and NIVOPOSTOP) have demonstrated meaningful improvements in event-free and disease-free survival, supporting the integration of perioperative and adjuvant immunotherapy into curative strategies. However, the data on the efficacy of immune checkpoint inhibitors in unresectable locally advanced head and neck squamous cell carcinoma remains inconsistent, underscoring the need for more precise patient selection and biomarker-driven approaches. Therapeutic strategies optimized for the timing and sequencing of immune checkpoint inhibitors in accordance with tumor microenvironment dynamics may improve clinical outcomes. Additionally, emerging immunotherapeutics, such as bispecific antibodies, oncolytic viruses, and chimeric antigen receptor T cell therapies, represents a promising frontier in the management of locally advanced head and neck squamous cell carcinoma. Considering the recent advances of the field, we aimed to synthesize current evidence and explore future directions for immunotherapy in locally advanced head and neck squamous cell carcinoma.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105145"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044419","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":"Immunometabolic heterogeneity in hepatocellular carcinoma: Transforming cold tumors into hot tumors","authors":"Yuanhao Xu,&nbsp;Jianguang Sun","doi":"10.1016/j.critrevonc.2026.105123","DOIUrl":"10.1016/j.critrevonc.2026.105123","url":null,"abstract":"<div><div>Despite significant progress in the field of immunotherapy for hepatocellular carcinoma (HCC), many patients still fail to respond to the treatment and develop \"cold tumors\". This review systematically clarifies the immunological and metabolic heterogeneity between “cold” and “hot” tumors in HCC—cold tumors are characterized by immunosuppression and more disordered metabolism, while hot tumors exhibit robust immune cell infiltration and active metabolism and respond favorably to immune checkpoint inhibitor therapy. We also summarize the biomarkers of HCC cold tumors and the therapeutic strategies for converting cold tumors to hot tumors, including cryoablation, immune combination therapy, nanocarrier-based approaches, vaccines, and metabolic interventions. Moreover, establishment of a hierarchical evidence system to evaluate these strategies revealed that immune combination therapy has sufficient clinical validation and significant clinical value, whereas other therapies require further research. We hope that this review will help improve the understanding of cold and hot HCC tumors and provide a novel perspective for the precision treatment of HCC.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105123"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961166","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":"Multi-omics profiling of intercellular immunometabolic heterogeneity highlights in lung cancer: Crosstalk mechanisms and resistance in the tumor–immune interface","authors":"Praise Audax Rukonge ,&nbsp;Vincent Kawuribi ,&nbsp;Yifan Sheng ,&nbsp;Qishu Wei ,&nbsp;Yan Kun ,&nbsp;Pascaline Niyodukunda ,&nbsp;Tianyu Wang ,&nbsp;Zhimeng Lu ,&nbsp;Yiyan Miao ,&nbsp;Kuang Xu ,&nbsp;Guiping yu","doi":"10.1016/j.critrevonc.2025.105094","DOIUrl":"10.1016/j.critrevonc.2025.105094","url":null,"abstract":"<div><div>Lung cancer’s tumor microenvironment (TME) is shaped by metabolic crosstalk between malignant and immune cells, driving immune evasion, heterogeneity, and resistance to immunotherapy. Tumor-derived metabolites such as lactate, adenosine, and kynurenine impair cytotoxic T cells and dendritic cells while promoting regulatory and suppressive immune subsets, creating a metabolically hostile niche that limits checkpoint inhibitor efficacy. Advances in multiomics including single-cell transcriptomics, proteomics, metabolomics, and spatial profiling have enabled high-resolution mapping of tumor–immune metabolic communication. Available evidence from various studies reveals metabolic subtypes, immune states, and spatial niches linked to resistance, including lactate accumulation, glutamine dependence, and adenosine signaling. This review uniquely synthesizes findings from latest literature (2009–2025) obtained from electronic database including PubMed, Google Scholar, Scopus and Web of Science, which integrates multi-omics data to define immunometabolic phenotypes (LM-high, CD73^high, KEAP1/NRF2^mutation) and pathways in lung cancer and highlights therapeutic strategies such as CD73/adenosine blockade, arginase and glutaminase inhibition, and metabolically engineered immune cells. Collectively, available evidence from various studies positions multi-omics profiling as a critical clinical tool. It enables the classification of tumors by dominant immunometabolic phenotype, thereby paving the way for biomarker-driven trials that rationally combine metabolic inhibitors with immunotherapy to overcome resistance.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105094"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844352","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":"Corrigendum to “Efficacy and safety of boron neutron capture therapy for locally recurrent head and neck cancer” [Crit. Rev. Oncol./Hematol. 218 (2026) 105101]","authors":"Xing Sun ,&nbsp;Yuchen Liu ,&nbsp;Zhiyi Xue ,&nbsp;Bo Cheng ,&nbsp;Ruiping Zhang ,&nbsp;Liping Li ,&nbsp;Weicheng Huang ,&nbsp;Qingxu Song ,&nbsp;Yufeng Cheng","doi":"10.1016/j.critrevonc.2026.105125","DOIUrl":"10.1016/j.critrevonc.2026.105125","url":null,"abstract":"","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105125"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013748","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":"Corrigendum to “A review of relative dose intensity and survival in patients with metastatic solid tumors” [Crit. Rev. Oncol. Hematol. 93 (2015) 203–210]","authors":"Laura J. Havrilesky ,&nbsp;Maureen Reiner ,&nbsp;Phuong Khanh Morrow ,&nbsp;Holly Watson ,&nbsp;Jeffrey Crawford","doi":"10.1016/j.critrevonc.2026.105163","DOIUrl":"10.1016/j.critrevonc.2026.105163","url":null,"abstract":"","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105163"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097751","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":"Harnessing the connection of the Wnt/beta-catenin pathway and other signaling pathways in glioblastoma multiforme","authors":"Ali Nakhaei ,&nbsp;Sadaf Afshari ,&nbsp;Elmira Mohatshami ,&nbsp;Mohammad Jalili-Nik ,&nbsp;Mahsa Jalali ,&nbsp;Kasim Sakran Abass ,&nbsp;Amir R. Afshari ,&nbsp;Prashant Kesharwani ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.critrevonc.2026.105127","DOIUrl":"10.1016/j.critrevonc.2026.105127","url":null,"abstract":"<div><div>Finding the proper and most effective treatment is significant because glioblastoma (GB), the most common and aggressive type of brain tumor, has been very hard for the healthcare system to deal with. Usually, standard treatments for this type of tumor take a long time to work. Even when they do, they can cause a lot of harmful side effects. One possible way to do this is to look at essential signaling pathways, especially the Wnt/beta-catenin pathway. This pathway controls some cellular connections in both healthy and unhealthy states of development. Recent findings have clarified the unique anticancer characteristics of the Wnt/beta-catenin pathway and its interrelations with other cellular pathways. These advantages have increased hopes for finding the right treatments for all types of cancer, even GB. A suggested answer focuses on critical signaling pathways, especially the Wnt/beta-catenin pathway. This pathway regulates various cellular interactions in both normal development and disease states. Recent discoveries have elucidated the distinctive anticancer properties of the Wnt/beta-catenin pathway and its interactions with other cellular pathways. These benefits have made people hopeful that they will be able to find the best treatment for all types of cancer, including GB. ‎</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105127"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994677","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 novel roles of RNA 5-methylcytosine modification in gastrointestinal tract cancers","authors":"Chenye Xi ,&nbsp;Ye Gao ,&nbsp;Huishan Jiang ,&nbsp;Yan Bian ,&nbsp;Chuting Yu ,&nbsp;Zheran Chen ,&nbsp;Wei Wang ,&nbsp;Lei Xin ,&nbsp;Han Lin ,&nbsp;Luowei Wang","doi":"10.1016/j.critrevonc.2026.105140","DOIUrl":"10.1016/j.critrevonc.2026.105140","url":null,"abstract":"<div><div>Gastrointestinal tract cancers, including esophageal carcinoma (ESCA), gastric cancer (GC), and colorectal carcinoma (CRC), are among the most common malignant tumors with high morbidity and mortality rates, posing an increasingly significant burden on social healthcare systems. Recent evidence revealing the association between RNA modifications (collectively termed epitranscriptomics) and the tumorigenesis of gastrointestinal tract cancers has provided new insights into their pathogenesis. Among these modifications, 5-methylcytosine (m5C) is one of the most prevalent. In this narrative review, we discuss the regulators and functions of RNA m5C modification, summarize the recent studies on the roles of m5C modification in gastrointestinal tract cancer cells, briefly explore the association between RNA m5C modification and the tumor microenvironment (TME), and provide insights into its potential clinical applications as well as the remaining challenges in utilizing m5C modification for the management of gastrointestinal tract cancers. This review is based on comprehensive literature searches conducted primarily in PubMed, with no restrictions on publication date. Relevant articles were selected according to their relevance to the scope and objectives of this review. Although increasing evidence has elucidated the molecular mechanisms by which m5C RNA modification regulates the development and progression of gastrointestinal tract cancers, clinical evidence supporting its application in early screening or as a therapeutic target remains limited. Current findings are mainly derived from experimental studies and exploratory clinical studies, suggesting the gap between mechanistic insights and clinical translation.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105140"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032066","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":"Transforming role of cancer associated fibroblasts: From therapeutic barriers to promising targets","authors":"Jing Chang ,&nbsp;Xiang Yu ,&nbsp;Nan Xiong ,&nbsp;Mingxuan Zhu ,&nbsp;Changjiang Yang ,&nbsp;Shidong Zhao ,&nbsp;Caihong Wang ,&nbsp;Shan Wang ,&nbsp;Yingjiang Ye ,&nbsp;Zhanlong Shen","doi":"10.1016/j.critrevonc.2026.105143","DOIUrl":"10.1016/j.critrevonc.2026.105143","url":null,"abstract":"<div><div>Tumor microenvironment (TME) serves as a critical mediator in cancer progression and treatment response, with cancer-associated fibroblasts (CAFs) recognized as core regulators of stromal-tumor interactions. As essential components of the TME, CAFs orchestrate tumor progression and therapy resistance through multifaceted mechanisms, including extracellular matrix (ECM) remodeling, angiogenesis modulation, and immune regulation, which collectively establish a complex regulatory network. Owing to their functional heterogeneity and potent tumor-promoting properties, CAFs have emerged as promising targets for novel anti-tumor therapies. This review highlights recent advances in the understanding of CAFs, focusing on their intricate interactions within the TME and their synergistic roles in promoting therapy resistance in cancer. Furthermore, we also discuss current CAF-targeted therapeutic strategies and ongoing clinical trials, and propose future research directions to further advance this field.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105143"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044442","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":"Circular RNAs: A key modulator of established cancer hallmarks","authors":"Md Abdus Samad ,&nbsp;Iftikhar Ahmad ,&nbsp;Shazi Shakil ,&nbsp;Syed Kashif Zaidi ,&nbsp;Samina Wasi ,&nbsp;Fahad A. Al-Abbasi ,&nbsp;Mohammad Hassan Alhashmi ,&nbsp;Shams Tabrez","doi":"10.1016/j.critrevonc.2026.105146","DOIUrl":"10.1016/j.critrevonc.2026.105146","url":null,"abstract":"<div><div>Cancer encompasses a diverse range of disease conditions marked by the uncontrolled growth of abnormal cells and is often associated with high recurrence rates. The development and progression of cancer are closely linked to the disruption of key molecular pathways that regulate cellular and tissue homeostasis. Among the various molecular players involved, circular RNAs (circRNAs) have gained increasing attention from the scientific community because of their aberrant expression in various cancer types, leading to its progression and development. CircRNAs represent a distinct class of covalently closed RNA with distinct tissue- and cell-specific expression profiles and are essential for controlling key cellular processes. It has emerged as a crucial regulatory molecule that contributes to numerous hallmarks of cancer, such as enhanced cell proliferation, growth suppression evasion, resistance to cell death, induction of angiogenesis, invasion and metastasis, maintenance of cancer stem cells, immune evasion, metabolic reprogramming, promotion of inflammation, impairment of DNA damage, genomic instability, non-mutational epigenetic reprogramming, and therapeutic resistance. This review aims to enhance our understanding on the role of circRNAs on several cancer hallmarks and promote further research into their underlying mechanism of action, to identify and utilize them as potential therapeutic strategies.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105146"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044475","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":"TROP-2–directed antibody–drug conjugates in advanced NSCLC: A systematic review and meta-analysis of efficacy, safety, and reconstructed survival outcomes","authors":"Muhammad Ansab ,&nbsp;Shree Rath ,&nbsp;Umama Alam ,&nbsp;Muhammad Burhan ,&nbsp;Hafiza Tooba Siddiqui ,&nbsp;Aakash Desai","doi":"10.1016/j.critrevonc.2025.105093","DOIUrl":"10.1016/j.critrevonc.2025.105093","url":null,"abstract":"<div><h3>Introduction</h3><div>Non-small cell lung cancer (NSCLC) represents the majority of lung cancer cases worldwide, with most patients diagnosed at advanced stages and limited by resistance to existing therapies. TROP-2, an epithelial cell surface glycoprotein overexpressed in many NSCLCs, has emerged as a promising therapeutic target for antibody–drug conjugates (ADCs). This study aims to systematically evaluate the efficacy and safety of TROP-2–directed ADCs in patients with advanced or metastatic NSCLC.</div></div><div><h3>Methods</h3><div>Electronic databases (PubMed, Embase, Clinical Trials and Cochrane Central) were searched up to November 2025 for studies reporting outcomes in advanced NSCLC patients treated with TROP-2–directed ADCs. Eligible studies included adult populations with advanced NSCLC that were treated with datopotamab deruxtecan, sacituzumab govitecan, or sacituzumab tirumotecan, and reported efficacy or safety outcomes. Pseudo–individual patient-level data for survival analyses were reconstructed from published Kaplan–Meier curves. Pooled effect sizes were estimated using random-effects meta-analytic models.</div></div><div><h3>Results</h3><div>Seven studies encompassing 1365 patients with advanced or metastatic NSCLC were included. The pooled median overall survival (OS) was 16.38 months (95 % CI: 11.17–22.96), and the median progression-free survival (PFS) was 6.08 months (95 % CI: 4.93–8.55). The objective response rate (ORR) across studies was 29 % (95 % CI: 19 %–39 %), with a disease control rate (DCR) of 79 % (95 % CI: 74 %–84 %). Subgroup analysis revealed patients with EGFR-mutated tumors had a significantly higher likelihood of response (risk ratio 1.70, 95 % CI: 1.11–2.61). Safety analysis showed treatment-emergent adverse events (TEAEs) in 98 % (95 % CI: 94 %–100 %), grade ≥ 3 TEAEs in 52 % (95 % CI: 38 %–67 %), and interstitial lung disease (ILD) in 9 % (95 % CI: 3 %–16 %).</div></div><div><h3>Conclusion</h3><div>TROP-2–directed ADCs demonstrate meaningful efficacy in previously treated advanced NSCLC, especially among EGFR-mutant and non-squamous histology patients, with survival and response outcomes superior to traditional chemotherapy. However, high rates of adverse events, particularly ILD, necessitate close monitoring. Further randomized and biomarker-driven studies are warranted to refine patient selection and optimize the therapeutic potential of these agents.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105093"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829129","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}