Critical reviews in oncology/hematology最新文献

{"title":"Immunotherapy-mediated cancer reversion: Possibilities and prospects","authors":"Emmanuel O. Oisakede ,&nbsp;Odunola Atitebi ,&nbsp;Raphael Igbarumah Ayo Daniel ,&nbsp;Eghosasere Egbon ,&nbsp;John Oluwatosin Alabi ,&nbsp;David B. Olawade","doi":"10.1016/j.critrevonc.2025.105103","DOIUrl":"10.1016/j.critrevonc.2025.105103","url":null,"abstract":"<div><div>Immunotherapy has revolutionized cancer treatment by enabling durable tumor control through immune activation. Emerging evidence suggests that beyond cytotoxic elimination, immune responses can reprogram malignant cells toward normalized, differentiated states, a phenomenon termed immunotherapy-mediated cancer reversion. This paradigm shift positions the immune system as a restorative rather than solely destructive force. This review synthesizes contemporary evidence on immunotherapy-mediated cancer reversion, evaluating mechanistic pathways and clinical implications across diverse malignancies to establish a conceptual framework for immune-driven phenotypic normalization. A comprehensive narrative review was conducted across PubMed, Web of Science, and Scopus databases, encompassing literature from 2015 to 2025. Evidence was synthesized thematically across immune checkpoint blockade, adoptive cell therapies, cytokine modulation, and microenvironmental remodeling. Immune-mediated reversion arises through coordinated epigenetic, metabolic, and microenvironmental reprogramming. Checkpoint inhibitors restore differentiation programs via IFNγ-driven chromatin remodeling, while CAR-T and NK-cell therapies induce metabolic normalization and epithelial restoration. Cytokine signaling and macrophage reprogramming reinforce reversion by modulating angiogenesis and stromal architecture. Clinical observations across melanoma, lung cancer, breast cancer, hematologic malignancies, and hepatocellular carcinoma support this restorative immune process. Single-cell and spatial omics identify transitional states bridging malignancy and normalcy. Immunotherapy-mediated cancer reversion represents a conceptual frontier shifting oncology from eradication to restoration. Future progress requires defining biomarkers, confirming mechanistic permanence, and redesigning clinical endpoints. As integrative immuno-epigenetic frameworks mature, immune-driven reversion may evolve from biological curiosity to clinically reproducible pathway toward durable remission and functional cure.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105103"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835514","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":"Sex differences in immunotherapy plus chemotherapy: A systematic review and meta-analysis","authors":"Salah Ameen Abdu ,&nbsp;Wafa Ali Asaad ,&nbsp;Muaadh Wdaan ,&nbsp;Ning Li","doi":"10.1016/j.critrevonc.2025.105069","DOIUrl":"10.1016/j.critrevonc.2025.105069","url":null,"abstract":"<div><h3>Background</h3><div>Sex-based differences in immune response and cancer biology may influence treatment outcomes with immunotherapy combinations. Comprehensive evidence regarding whether biological sex affects the efficacy of immune checkpoint inhibitor plus chemotherapy regimens remains incomplete.</div></div><div><h3>Methods</h3><div>Following PRISMA guidelines, we systematically searched five databases through May 2025 for randomized controlled trials comparing immune checkpoint inhibitors plus chemotherapy versus chemotherapy alone in any cancer type. We performed a comprehensive meta-analysis with sex-stratified survival data, subgroup analyses across cancer types and treatment regimens, meta-regression, interaction testing with false discovery rate correction, and publication bias assessment.</div></div><div><h3>Results</h3><div>Seventy-nine trials enrolling 50,046 patients (30,503 males, 19,543 females) met inclusion criteria. Combination therapy significantly improved survival in both sexes: overall survival hazard ratios were 0.76 (95 % CI 0.73–0.78) in males and 0.78 (95 % CI 0.75–0.81) in females, representing 24 % and 22 % mortality reductions, respectively. Progression-free survival improved by 39 % in males (HR 0.61, 95 % CI 0.57–0.64) and 34 % in females (HR 0.66, 95 % CI 0.62–0.70). Overlapping confidence intervals and formal interaction testing revealed no statistically significant sex-based differences across cancer types, immunotherapy agents, histological subtypes, or chemotherapy backbones.</div></div><div><h3>Conclusions</h3><div>Immune checkpoint inhibitors with chemotherapy provide significant and equivalent survival benefits for both male and female patients across cancer types. Treatment decisions should therefore be guided by tumor characteristics, not patient sex. These results support equitable treatment access and highlight the necessity for continued sex-stratified data reporting in clinical trials.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105069"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710521","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":"Potential strategies to improve the therapeutic efficacy of oncolytic viruses for cancer through T and NK cells targeting","authors":"Chuanjian Wu ,&nbsp;Hanzhang Liu ,&nbsp;Yujie Shi ,&nbsp;Jie Tang ,&nbsp;Rong Sun ,&nbsp;Xudong Han ,&nbsp;Yihui Fan","doi":"10.1016/j.critrevonc.2025.105086","DOIUrl":"10.1016/j.critrevonc.2025.105086","url":null,"abstract":"<div><div>Oncolytic viruses (OVs) elicit potent tumor lysis and remodel the tumor microenvironment (TME) to activate adaptive and innate immunity, yet their efficacy depends critically on T and NK cell responses. Here, we review recent advances in the characterization and engineering of OVs to enhance lymphocyte-mediated tumor control. CD8⁺ cytotoxic T cells and CD4⁺ helper T cells drive durable antitumor immunity through OV-enhanced antigen presentation, memory formation, and modulation of Tregs, whereas T cell exhaustion and checkpoint interactions remain key barriers. Arming OVs with cytokines, chemokines, bispecific engagers, or metabolic modulators enhances effector T-cell expansion, infiltration, and cytotoxicity in solid tumors. In parallel, NK cells—whose efficacy is often limited by poor intratumoral activity and antiviral competition—are increasingly harnessed by OV platforms expressing immune stimulators or checkpoint modulators. Combination strategies with targeted therapies, checkpoint blockade, or adoptive NK/T cell transfer further potentiate therapeutic efficacy. Importantly, although OVs may inadvertently amplify dominant antiviral responses at the expense of antitumor activity, strategies incorporating tumor antigen encoding and TME reprogramming can overcome this limitation. Collectively, these findings underscore the central role of T and NK cells in OV-based immunotherapy and highlight rational arming and combination approaches to improve tumor control and long-term protection.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105086"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770172","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":"HER2 in gynecological malignancies: Bridging the gap between standardized pathological assessment and precision therapy","authors":"Gian Franco Zannoni ,&nbsp;Angela Santoro ,&nbsp;Giuseppe Angelico ,&nbsp;Antonio D’Amati ,&nbsp;Giulia Scaglione ,&nbsp;Xavier Matias-Guiu ,&nbsp;Natalia Buza","doi":"10.1016/j.critrevonc.2025.105046","DOIUrl":"10.1016/j.critrevonc.2025.105046","url":null,"abstract":"<div><div>HER2 is a transmembrane tyrosine kinase receptor involved in cell proliferation, survival, and differentiation. While its role in breast and gastric cancers is well established, increasing attention is being paid to HER2 expression in gynecologic malignancies. In endometrial cancer, HER2 overexpression is most commonly associated with serous endometrial carcinoma (SEC), where it occurs in approximately 30 % of cases and correlates with poor prognosis, platinum resistance, and TP53 mutations. HER2-low expression, defined by IHC scores of 1 + or 2 + without gene amplification, has also emerged as a potential therapeutic target. Trastuzumab-based therapy has shown survival benefit in HER2-positive SEC, leading to its inclusion in current treatment guidelines. In ovarian cancer, HER2 amplification is most frequent in mucinous subtypes but also appears in clear cell and endometrioid carcinomas. The prognostic value remains debated, though recent trials of antibody–drug conjugates (e.g., T-DXd) show promise. In cervical cancer, HER2 is more commonly expressed in adenocarcinomas, particularly gastric-type variants, with gene amplification linked to adverse features. HER2 positivity is rare in vulvar and vaginal cancers but is notably present in extramammary Paget disease. Accurate HER2 testing relies on IHC with ISH confirmation and may be complemented by NGS or PCR in select cases. Diagnostic challenges include variable scoring systems, intratumoral heterogeneity, and HER2-low classification. Standardization of testing criteria and further clinical validation of HER2-targeted strategies across gynecologic tumors are essential to guide personalized therapy and improve outcomes.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105046"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679681","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":"Revolutionizing early detection of TNBC: The rise of non-invasive biomarkers and next-gen diagnostic strategies","authors":"Aqsa Ashraf ,&nbsp;Syeda Zainab Amir ,&nbsp;Laiba Jahangir ,&nbsp;Emma Daniel ,&nbsp;Muhammad Mustafa","doi":"10.1016/j.critrevonc.2025.105107","DOIUrl":"10.1016/j.critrevonc.2025.105107","url":null,"abstract":"<div><div>Triple negative breast cancer (TNBC) is the most malignant subtype of breast cancer (BC), which accounts for 10–20 % of BC incidences, and its early diagnosis is pivotal to curing the disease. Tissue biopsies, surgical biopsies, and needle biopsies, currently the preferred methods for acquiring tumor molecular characterization, are invasive and ineffective in capturing the core driving factors of tumor heterogeneity, rendering them incapable of portraying the complete molecular landscape. Non-invasive approaches permit tumor heterogeneity to be studied more comprehensively by sampling biofluids, including blood, urine, and saliva, and extracting tumor components such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), circulating proteins, extracellular vesicles (EVs), and microRNAs (miRNAs). We reviewed emerging non-invasive biomarkers; non-invasive molecular imaging modalities coupled with omics and artificial intelligence (AI) for stratification and early TNBC detection. The new diagnostic biomarkers can revolutionize early diagnosis and help clinicians to strategize treatment choices for a better prognosis in TNBC.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105107"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893551","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":"Chondrosarcoma: Clinical behavior, molecular mechanisms, and emerging therapeutic strategies","authors":"Mark Agulnik ,&nbsp;Breelyn A. Wilky ,&nbsp;Steven W. Thorpe ,&nbsp;Lee M. Zuckerman","doi":"10.1016/j.critrevonc.2025.105075","DOIUrl":"10.1016/j.critrevonc.2025.105075","url":null,"abstract":"<div><div>Chondrosarcoma is the second most common primary malignant bone tumor. While the overall 5-year survival rate is approximately 70–75 %, high-grade tumors and aggressive chondrosarcoma subtypes are associated with a particularly poor prognosis. Wide surgical resection remains the standard treatment for localized disease and can be curative; however, effective therapies for unresectable or metastatic chondrosarcoma are needed. Preclinical research and analyses of patient tumor samples have identified several molecular mechanisms driving chondrosarcoma development and progression, including mutations in isocitrate dehydrogenases types 1 and 2 (<em>IDH1/2</em>) and <em>TP53</em>, hyperactivation of protumorigenic signaling pathways, and programmed cell death ligand 1 (PD-L1) expression. This review explores chondrosarcoma subtypes, diagnostic approaches, prognostic factors, and molecular alterations, followed by a discussion of current and emerging treatment strategies. Emphasis is placed on clinical trials investigating targeted therapies or immunotherapies for advanced chondrosarcoma, including inhibitors of IDH1/2 and multiple kinases, death receptor 5 agonism, and other potential new therapeutic approaches.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105075"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758660","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":"From diagnosis and treatment to prognosis: Clinical prospects of artificial intelligence in multimodal research of hepatocellular carcinoma","authors":"Weili Jia ,&nbsp;Xiaoyang Duan ,&nbsp;Qianyun Yao ,&nbsp;Rong Liu ,&nbsp;Chee Leong Cheng","doi":"10.1016/j.critrevonc.2025.105102","DOIUrl":"10.1016/j.critrevonc.2025.105102","url":null,"abstract":"<div><h3>Purpose</h3><div>This review aims to critically evaluate the evolving role and clinical readiness of multimodal Artificial Intelligence (AI) in Hepatocellular Carcinoma (HCC), addressing the fundamental limitations of traditional single-modality approaches in characterizing tumor heterogeneity.</div></div><div><h3>Principal results</h3><div>Integrative analysis of heterogeneous data sources—specifically radiomics, pathomics, genomics, and clinical variables—demonstrates superior performance over uni-modal baselines in early diagnosis, microvascular invasion prediction, and immunotherapy response monitoring. However, the observed performance in published studies may present an \"iceberg effect,\" where high internal validation metrics mask diminished generalizability to external cohorts, a discrepancy potentially attributable to publication biases and data drift. Comparative assessment indicates that while Late Fusion strategies currently provide greater robustness for clinical workflows, Early Fusion architectures hold promise for deeper biological insight. Furthermore, although Generative AI can alleviate data scarcity through synthetic augmentation, it introduces unaddressed risks of diagnostic hallucinations.</div></div><div><h3>Scientific value added</h3><div>Unlike descriptive surveys, this work highlights the critical necessity of shifting from passive data acquisition to active sensing and transitioning from correlation-based \"black box\" models to Causal AI and Chain-of-Thought reasoning to establish clinical trust.</div></div><div><h3>Conclusions</h3><div>We conclude that bridging the translational gap requires immediate adherence to standardized reporting guidelines like TRIPOD-AI to ensure reproducibility. The future of HCC precision medicine lies in evolving toward pre-trained Foundation Models and \"Digital Twins,\" transforming clinical management from empirical reliance to mechanism-driven computational intelligence over the next decade.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105102"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835559","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":"Chimeric antigen receptor T-cell therapy and immune effector cell-associated neurotoxicity syndrome: A meta-analysis","authors":"Ashwini Thirugnanam ,&nbsp;Karun Donthineni ,&nbsp;Marco Mammi ,&nbsp;Jessie Hundel ,&nbsp;Diana Munteh ,&nbsp;Fabio D’Amore ,&nbsp;Adomas Bunevicius ,&nbsp;Rania A. Mekary","doi":"10.1016/j.critrevonc.2025.105095","DOIUrl":"10.1016/j.critrevonc.2025.105095","url":null,"abstract":"<div><h3>Background</h3><div>Chimeric antigen receptor (CAR) T-cell therapy, a form of adoptive immunotherapy, has expanded treatment options for various hematologic malignancies. However, CAR T therapy is associated with a range of side effects, including immune effector cell-associated neurotoxicity syndrome (ICANS), with variable incidence and severity.</div></div><div><h3>Objective</h3><div>To evaluate the incidence and characteristics of ICANS following CAR T therapy in different hematological diseases, with a focus on product-specific variations.</div></div><div><h3>Methods</h3><div>We searched PubMed, Embase, and Cochrane Library through 2/16/2024. Pooled incidence and 95 % confidence intervals (CIs) for ICANS (overall, more severe, and less severe) were estimated via a random-effects model. Separate meta-analyses were conducted for each lymphoma type – large B-cell lymphoma (LBCL), multiple myeloma (MM), and mantle cell lymphoma (MCL).</div></div><div><h3>Results</h3><div>Of 259 articles reviewed, 30 studies were meta-analyzed. Among LBCL patients, the incidence of ICANS appeared lower with tisagenlecleucel (16.5 %, 95 % CI: 12.9–20.9; n = 1108 patients) than with axicabtagene ciloleucel (45.6 %, 95 % CI: 39.6–51.7; n = 1579). In MM patients, the incidence appeared lower with ciltacabtagene autoleucel (10.4 %, 95 % CI: 5.2–19.9; n = 348) than with idecabtagene vicleucel (18.3 %; 95 % CI: 15.4–21.5; n = 631). For MCL patients (n = 198), brexucabtagene autoleucel showed a high overall incidence of ICANS (61.2 %; 95 % CI: 54.2–67.8), with more severe events (32.9 %; 95 % CI: 26.7 %-39.7 %) slightly exceeding less severe ones (28.6 %; 95 % CI: 22.7 %-35.3 %).</div></div><div><h3>Conclusion</h3><div>Tisa-cel and cilta-cel showed a more favorable ICANS safety profile in LBCL and MM patients, respectively, while brexu-cel showed a higher ICANS incidence in MCL patients. Further comparative studies are needed to adjust for treatment-related confounders.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105095"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835526","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":"To ablate or not to ablate? Outcomes of local ablative treatments (LAT) for oncogene addicted (OA) oligo-metastatic (OM) non-small cell lung cancer (NSCLC): A systematic review","authors":"Fabrizio Citarella ,&nbsp;Cristina Fragale ,&nbsp;Matteo Fiorenti ,&nbsp;Maria Luisa Di Guglielmo ,&nbsp;Noemi Mindicini ,&nbsp;Alessio Cortellini ,&nbsp;Alessandro Russo ,&nbsp;Giuseppe Bronte","doi":"10.1016/j.critrevonc.2025.105096","DOIUrl":"10.1016/j.critrevonc.2025.105096","url":null,"abstract":"<div><div>Oncogene-addicted non-small cell lung cancer (NSCLC) encompasses distinct molecular phenotypes, each associated with specific clinical behavior and variable sensitivity to targeted therapies. Therapeutic advancements in the field enhanced clinical outcomes and overall prognostic improvement. Beyond the molecular profile, disease burden serves as a predictive marker for treatment response and overall prognostic outcomes. The current disease staging categorizes patients based on the number and sites of metastatic involvement. In this context, the addition of local ablative therapies (LAT) is candidate to enhance or prolong the effectiveness of standard systemic therapies. Our systematic review aims to summarize current evidence dealing with the outcomes of LAT in the context of oncogene addicted NSCLC. Over response results, we also reported side effects whenever available.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105096"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800848","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":"Long noncoding RNAs as master regulators of autophagy in cancer: Implications for chemoresistance and therapeutic sensitization","authors":"Zhenwang Zhang ,&nbsp;Wenqiang Peng ,&nbsp;Baoqing Zhao ,&nbsp;Lei Meng ,&nbsp;Ji Pan","doi":"10.1016/j.critrevonc.2025.105113","DOIUrl":"10.1016/j.critrevonc.2025.105113","url":null,"abstract":"<div><div>Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of autophagy, a fundamental cellular process that maintains homeostasis under stress but also contributes to cancer progression and therapeutic resistance. Recent studies reveal that lncRNAs orchestrate autophagy through diverse mechanisms, including acting as competing endogenous RNAs (ceRNAs), directly interacting with core autophagy machinery such as Beclin1 and ATG proteins, or modulating key signaling pathways like PI3K/AKT/mTOR, Wnt/β-catenin, and HIF-1α. By fine-tuning autophagic activity, lncRNAs shape tumor cell survival, proliferation, and response to chemotherapy, targeted therapy, and radiotherapy. Importantly, the impact of autophagy is highly context-dependent: in some settings, lncRNA-driven autophagy promotes drug resistance and tumor progression, whereas in others, autophagy induction exerts tumor-suppressive effects. Targeting the lncRNA–autophagy axis therefore offers dual opportunities: inhibiting pro-autophagic lncRNAs to overcome chemoresistance, or restoring anti-autophagic lncRNAs to sensitize tumors to treatment. Advances in RNA-based therapeutics and delivery platforms, coupled with small-molecule autophagy modulators and immunotherapy, provide new avenues for translational applications. In this review, we summarize current knowledge of lncRNA-mediated autophagy in cancer, highlight its role in therapeutic resistance and sensitization, and discuss challenges and opportunities for clinical translation.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105113"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901851","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}