Cancer treatment reviews最新文献

{"title":"Risk of QTc prolongation, and major cardiovascular adverse events associated with CDK4/6 inhibitors in hormone receptor-positive HER2-negative breast cancer – A systematic review and meta-analysis","authors":"Yee-Yin Hoo ,&nbsp;Wei-Wei Sia ,&nbsp;Sharminii Jaya-Prakason ,&nbsp;Bogda Koczwara ,&nbsp;Yek-Ching Kong ,&nbsp;Joe-Elie Salem ,&nbsp;Agnès Dechartres ,&nbsp;Nirmala Bhoo-Pathy","doi":"10.1016/j.ctrv.2025.103069","DOIUrl":"10.1016/j.ctrv.2025.103069","url":null,"abstract":"<div><h3>Background</h3><div>Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) improve survival in HR+/HER2- breast cancer, but agent-specific cardiotoxicity remains a concern. We evaluated the risk of QTc prolongation, and other cardiovascular adverse events (CVAEs) associated with ribociclib, palbociclib, and abemaciclib.</div></div><div><h3>Method</h3><div>We conducted a systematic review and meta-analysis (up to May 31st, 2025), assessing QTc prolongation and other CVAEs in patients with HR+/HER2- breast cancer receiving CDK4/6i plus endocrine therapy versus endocrine therapy alone<strong>.</strong> (PROSPERO: CRD42023460559; UICC Technical Fellowship (TF-20–716796).</div></div><div><h3>Results</h3><div>Twenty-three studies (22 RCTs, 1 cohort) were included. CDK4/6i increased the risk of grade 3/4 QTc prolongation (RR 1.83, 95% CI 1.23–2.74), driven by ribociclib (RR 1.95, 95% CI 1.27–2.98). Palbociclib showed no association, whereas no abemaciclib trials reported QTc data. VTE risk was elevated overall (RR 2.57, 95% CI 1.53–4.32), highest with abemaciclib (RR 5.14, 95% CI 3.09–8.54), while palbociclib was borderline (RR 2.13, 95% CI 0.99–4.57). Subgroup analyses revealed no consistent effect modifiers for ribociclib (QTc) or abemaciclib (VTE). No significant increase was observed for other composite CVAEs (RR 0.99, 95% CI 0.83–1.19) or for individual CVAEs. A hypothesis-generating signal for supraventricular arrhythmias was noted with abemaciclib (RR 3.87, 95% CI 1.19–12.53), based on sparse events. Heterogeneity was low across analyses.</div></div><div><h3>Conclusion</h3><div>Our findings mandate drug-tailored rather than class-wide cardiovascular monitoring in patients receiving CDK4/6i: ribociclib warrants routine ECG surveillance, abemaciclib requires intensified monitoring for VTE, and palbociclib shows no consistent signal but still merits vigilance.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103069"},"PeriodicalIF":10.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical performance of tumor-informed versus tumor-agnostic ctDNA assays for colorectal cancer recurrence: A systematic review and diagnostic accuracy meta-analysis","authors":"Daniel G. Camblor ,&nbsp;Belén Martínez-Castedo ,&nbsp;Jorge Martín-Arana ,&nbsp;Francisco Gimeno-Valiente ,&nbsp;Blanca García-Micó ,&nbsp;Francisco Martínez-Picó ,&nbsp;Víctor Seguí ,&nbsp;Miguel García-Bartolomé ,&nbsp;Diego González ,&nbsp;Alejandro Guimera ,&nbsp;Marisol Huerta ,&nbsp;Susana Roselló ,&nbsp;Valentina Gambardella ,&nbsp;Desamparados Roda ,&nbsp;Leontios Pappas ,&nbsp;Aparna Parikh ,&nbsp;Juan Antonio Carbonell-Asins ,&nbsp;Andrés Cervantes ,&nbsp;Noelia Tarazona","doi":"10.1016/j.ctrv.2025.103066","DOIUrl":"10.1016/j.ctrv.2025.103066","url":null,"abstract":"<div><div>In patients with early-stage colorectal cancer (CRC), circulating tumor DNA (ctDNA) testing is increasingly used to detect minimal residual disease (MRD) after curative-intent surgery. This information can guide decisions on adjuvant chemotherapy and surveillance. Two main approaches exist, tumor-informed (TI) and tumor-agnostic (TA), however, their diagnostic accuracy in clinical practice remains unclear. We conducted a bivariate diagnostic meta-analysis to compare sensitivity and specificity of TI versus TA ctDNA assays for detecting recurrence in patients with resected CRC. Subgroup analyses were performed based on landmark versus serial sampling strategies. In the serial-sampling setting, TI assays demonstrated markedly higher sensitivity than TA assays (0.88 vs. 0.59; p = 0.001), with no significant differences in false-positive rates. The landmark analyses did not show statistically significant differences between approaches. The results underscore the importance of sampling strategy when selecting a ctDNA test. When longitudinal monitoring is feasible, TI assays provide the most reliable detection of recurrence. This meta-analysis supports tailoring ctDNA testing to the clinical context, prioritizing TI approaches for serial surveillance to better guide adjuvant decision-making and improve patient outcomes.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103066"},"PeriodicalIF":10.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequencing antibody–drug conjugates in metastatic breast cancer: A systematic review","authors":"Luiz F. Costa de Almeida ,&nbsp;Luís Felipe Leite ,&nbsp;Anelise Poluboiarinov Cappellaro ,&nbsp;Lucas Diniz da Conceição ,&nbsp;Mariana Macambira Noronha ,&nbsp;Jessé Lopes da Silva ,&nbsp;Andreia Cristina de Melo ,&nbsp;Felipe Batalini ,&nbsp;Paolo Tarantino","doi":"10.1016/j.ctrv.2025.103067","DOIUrl":"10.1016/j.ctrv.2025.103067","url":null,"abstract":"<div><h3>Background</h3><div>Antibody–drug conjugates (ADCs) have redefined the treatment landscape of metastatic breast cancer (mBC), offering durable responses across all subtypes. As multiple ADCs with similar payloads become available for the same patient over the course of the disease, determining the optimal sequencing strategy has become an urgent need, particularly given concerns about cross-resistance and reduced efficacy.</div></div><div><h3>Methods</h3><div>A literature search identified 1868 citations, of which 23 studies (n = 2934 patients) met the inclusion criteria, encompassing ten full-text publications and 13 abstracts. Data on clinical subtypes, sequencing strategies, efficacy outcomes, and real-world evidence (RWE) were extracted and analyzed.</div></div><div><h3>Results</h3><div>In HER2-low mBC, initial ADC exposure produced higher response rates and longer PFS than subsequent ADCs, with median PFS declining from 5.1–7.6 months to 2.1–3.1 months and OS from 16.5–22.8 months to 5.6–8.0 months. In HER2-positive disease, clinical activity was partially preserved with the second ADC, particularly when T-DXd followed T-DM1, with sustained PFS. TNBC and HR+/HER2– cohorts showed a consistent decline in efficacy with second ADC exposure (PFS 2.5–3.1 months). Evidence indicates that switching ADC payloads mitigates cross-resistance, with improved ORR and PFS2 compared to same-payload sequences. Bridging chemotherapy between ADCs did not compromise efficacy and, in some cohorts, yielded a longer PFS than direct sequencing with another ADC with the same payload.</div></div><div><h3>Conclusion</h3><div>Emerging evidence indicates that sequential ADC use can be effective despite some cross-resistance, especially when distinct payload mechanisms are employed. Clinical use should consider payload type, timing, and breast cancer subtype, but toxicities remain critical for decision-making. Research providing insights into resistance mechanisms and biomarkers is needed for personalized approaches.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103067"},"PeriodicalIF":10.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular senescence: A novel mechanism of therapeutic resistance in prostate cancer","authors":"Claire Lin ,&nbsp;Matthew J. Hadfield ,&nbsp;Amol Rathore ,&nbsp;Maximilian Pinho-Schwermann ,&nbsp;Shengliang Zhang ,&nbsp;Shaolei Lu ,&nbsp;Petra den Hollander ,&nbsp;Sendurai A. Mani ,&nbsp;Attila A. Seyhan ,&nbsp;Ariana Santopietro ,&nbsp;Anthony Mega ,&nbsp;Liang Cheng ,&nbsp;Wafik S. El-Deiry ,&nbsp;Benedito A. Carneiro","doi":"10.1016/j.ctrv.2025.103061","DOIUrl":"10.1016/j.ctrv.2025.103061","url":null,"abstract":"<div><div>Prostate cancer (PCa) is a leading cause of cancer-related morbidity and mortality. Despite the efficacy of androgen deprivation therapy (ADT), patients with advanced PCa eventually progress to a lethal castration-resistant disease state. Cellular senescence represents a stable growth arrest induced by stress signaling cascades or cancer therapeutics, and escape from a senescent state may be implicated in the development of castration resistance. We discuss the mechanisms promoting cellular senescence in PCa and its contribution to therapeutic resistance to ADT, PARP inhibitors, chemotherapy, and radiation. We also summarize the potential of senolytic and senomorphic therapies in targeting senescent prostate cancer cells in the setting of therapy-induced senescence.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103061"},"PeriodicalIF":10.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145662886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone metastases in NSCLC: Modern paradigms in management and supportive care","authors":"Gabriele Minuti ,&nbsp;Giorgia Pasqualini ,&nbsp;Alice Avancini ,&nbsp;Niccolò Giaj-Levra ,&nbsp;Francesca Colonese ,&nbsp;Alessandro Di Federico ,&nbsp;Alessandra Fozza ,&nbsp;Michele Montrone ,&nbsp;Emanuela Olmetto ,&nbsp;Edoardo Pastorello ,&nbsp;Maria Lucia Reale ,&nbsp;Silvia Teresa Riva ,&nbsp;Elisa Roca ,&nbsp;Claudio Sini ,&nbsp;Giuseppe Viscardi ,&nbsp;Sara Pilotto ,&nbsp;Francesco Passiglia","doi":"10.1016/j.ctrv.2025.103051","DOIUrl":"10.1016/j.ctrv.2025.103051","url":null,"abstract":"<div><div>Bone metastases (BoMs) are a frequent complication in advanced non-small-cell lung cancer (NSCLC), affecting approximately one third of patients at diagnosis and 35–60 % during the disease course. BoMs increase the risk of skeletal-related events (SREs), which have a detrimental impact on prognosis, performance status, and quality of life (QoL). Management of BoMs in NSCLC requires a multimodal approach. Although systemic anti-cancer therapies remain the cornerstone, the optimal management of BoMs in NSCLC also encompasses bone-targeted agents (BTAs) such as bisphosphonates and denosumab, local treatments including radiotherapy and surgical interventions, and supportive care strategies aimed at preventing SREs, alleviating pain, preserving mobility, and maintaining QoL. This review provides an updated overview of best practices for managing BoMs in NSCLC, covering diagnostic work‑up, therapeutic strategies, and the growing role of multidisciplinary care. It emphasizes the importance of supportive interventions, including nutrition and physical activity, to optimize outcomes in the era of targeted and immune-based therapies, alongside comprehensive simultaneous care.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103051"},"PeriodicalIF":10.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic utility of urinary cell-free DNA in non-urothelial cancer: a systematic review, meta-analysis, & network meta-analysis","authors":"Shugo Yajima,&nbsp;Kohei Hirose,&nbsp;Hitoshi Masuda","doi":"10.1016/j.ctrv.2025.103047","DOIUrl":"10.1016/j.ctrv.2025.103047","url":null,"abstract":"<div><h3>Purpose</h3><div>Urinary cell-free DNA (ucfDNA) offers a noninvasive approach for cancer detection, but its diagnostic utility in non-urothelial cancers remains unclear. We systematically evaluated the diagnostic and prognostic value of ucfDNA for these cancers and compared its performance with other liquid biopsies through network <em>meta</em>-analysis.</div></div><div><h3>Experimental design</h3><div>We conducted a systematic search of PubMed, Cochrane Library, and other databases for studies from 2010 to 2025 evaluating ucfDNA for diagnosing or predicting prognosis in non-urothelial cancers. Primary outcomes were pooled diagnostic sensitivity and specificity; secondary outcomes included prognostic hazard ratios (HRs). Study quality was assessed using QUADAS-2, and Bayesian hierarchical models were employed for robust estimates.</div></div><div><h3>Results</h3><div>Twenty-eight studies involving 4,423 participants were included. Overall pooled sensitivity was 0.80 (95 % CI, 0.75–0.85) and specificity was 0.96 (95 % CI, 0.88–0.98), with significant heterogeneity (<em>I</em>² &gt; 82 %). Subgroup analysis of studies targeting short amplicons (&lt;70 bp) showed improved specificity of 0.98 and substantially reduced heterogeneity (<em>I</em>² = 0 % for specificity). Limited post-treatment ucfDNA reduction was a strong predictor of poor prognosis (pooled HR, 2.76; 95 % CI, 1.94–3.91). Exploratory network <em>meta</em>-analysis in non-small cell lung cancer comparing urine, plasma, and sputum showed overlapping confidence intervals, though the limited available data and wide confidence intervals preclude definitive conclusions regarding comparative performance. Mutation-based assays demonstrated significantly higher specificity than methylation-based approaches (99 % vs. 72 %, <em>P</em> &lt; 0.01).</div></div><div><h3>Conclusions</h3><div>ucfDNA demonstrates high diagnostic specificity for non-urothelial cancers and provides significant prognostic information. Optimizing assays for ultrashort DNA fragments is critical for enhancing performance and reducing variability. These findings support the potential utility of ucfDNA, particularly as a complementary tool alongside established liquid biopsies like plasma cfDNA, to enhance non-invasive cancer diagnosis and monitoring. Its role as a standalone diagnostic requires further validation, and method standardization remains essential for broad implementation.</div></div><div><h3>Clinical trial registration</h3><div>PROSPERO CRD420251073863.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103047"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving treatment strategies for resectable gastric cancer: Bridging Asia-West disparities toward personalized and integrated therapy","authors":"Xuesong Zhao ,&nbsp;Qianyun Hao ,&nbsp;Maria Alsina ,&nbsp;Daniel Acosta ,&nbsp;Florian Castet ,&nbsp;Eduardo Terán ,&nbsp;Kreina Vega Cano ,&nbsp;Tamara Saurí ,&nbsp;Ismael Macías ,&nbsp;Takaki Yoshikawa ,&nbsp;Sandra Castro ,&nbsp;Hirokazu Shoji ,&nbsp;Florian Lordick ,&nbsp;Zhanlong Shen ,&nbsp;Tian V. Tian ,&nbsp;Teresa Macarulla","doi":"10.1016/j.ctrv.2025.103041","DOIUrl":"10.1016/j.ctrv.2025.103041","url":null,"abstract":"<div><div>Gastric cancer (GC) remains a significant global health burden. Both Asian countries and Western nations, represented by Europe and North America, have long been pioneers in GC research and continue to lead advancements in the field. However, notable differences have historically existed between these regions in the treatment of resectable GC. In recent years, increasing convergence between Asian and Western approaches has emerged, driven by the growth of global collaborative studies. New definitive evidence suggests that the therapeutic landscape for resectable GC may undergo a significant transformation. In this review, we comprehensively examine the evolution of surgical approaches and perioperative chemotherapy strategies in Asia and the West. We summarize key clinical trials, highlight persistent survival disparities, and provide insight into current trends in perioperative management, including the recent advances in molecularly driven perioperative treatments. Finally, we outline key considerations for future multicenter perioperative trials to further guide global clinical practice.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103041"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiogenesis and thymic epithelial tumors: from preclinical insights to different therapeutic lines and combination strategies","authors":"D. Miliziano ,&nbsp;C. Sciortino ,&nbsp;S. Manglaviti ,&nbsp;M. Ganzinelli ,&nbsp;A. Lopez-Gutierrez ,&nbsp;M. Occhipinti ,&nbsp;C. Proto ,&nbsp;F. De Braud ,&nbsp;B. Besse ,&nbsp;G. Lo Russo ,&nbsp;J. Remon","doi":"10.1016/j.ctrv.2025.103049","DOIUrl":"10.1016/j.ctrv.2025.103049","url":null,"abstract":"<div><div>Thymic epithelial tumors (TETs) are rare thoracic malignancies for which surgical resection remains the mainstay treatment, even in advanced stages. For patients with metastatic disease, platinum-based chemotherapy represents the current standard of care in the first-line, with no standard treatment at progression. Much preclinical evidence supports a potential role of angiogenesis in the pathogenesis and progression of TETs. This biological rationale has led to assess the efficacy of several antiangiogenic agents, either in monotherapy or in combination in pre-treated metastatic TET, reporting a clinical meaningful outcome. Despite this efficacy several challenges remain such as the optimal place of angiogenic agents in the treatment sequence, whether they should be applied as monotherapy or in combination, as well as the potential clinical activity of sequential antiangiogenic agents with different mechanisms of action. In this review, we provide a comprehensive overview of the preclinical and clinical evidence supporting angiogenesis as a therapeutic target in TETs. We also propose potential treatment algorithms based on the current literature, while highlighting the ongoing challenges in defining optimal dosing strategies and treatment sequences in this rare disease.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103049"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transformation from EGFR-mutant lung adenocarcinoma to small-cell lung cancer: from clonal evolution to lineage reprogramming","authors":"Haoxin Wang ,&nbsp;Nan Gao ,&nbsp;Lu Wang ,&nbsp;Feiran Yang ,&nbsp;Bin Liu ,&nbsp;Xiwen Hu ,&nbsp;Yufeng Zhao ,&nbsp;Rui Sha ,&nbsp;Xiurong Li ,&nbsp;Huijie Li","doi":"10.1016/j.ctrv.2025.103044","DOIUrl":"10.1016/j.ctrv.2025.103044","url":null,"abstract":"<div><div>EGFR-mutant lung adenocarcinoma (LUAD) that transforms into small-cell lung cancer (SCLC) following targeted therapy represents a clinically significant mechanism of acquired resistance, occurring in approximately 3–14 % of cases. This transformed variant, referred to as SCLC after transformation (SCLC-AT), follows an aggressive clinical course and carries a poor prognosis. SCLC-AT retains the original EGFR mutation but significantly down-regulates EGFR protein expression, eliminating its dependence on EGFR signaling while simultaneously acquiring a neuroendocrine phenotype. In nearly all cases, bi-allelic inactivation of both TP53 and RB1 is observed. In this overview, we provide a detailed examination of the molecular mechanisms underlying the transition from EGFR-mutant LUAD to SCLC. By integrating two primary biological concepts, clonal evolution and lineage reprogramming, we examine recent advances concerning the original cell or cells involved, as well as the genetic and epigenetic reprogramming and signaling pathway changes. While the transformation to SCLC is currently considered genetically and epigenetically irreversible, preclinical interventions targeting EZH2, AURKA, and DLL3 have shown potential in reversing the neuroendocrine phenotype or improving tumor immunogenicity. Future research should utilize single-cell and spatial multi-omics technologies to develop predictive models that can facilitate the early detection of impending transformation and guide precision therapies, ultimately enhancing patient outcomes.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103044"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-T cell therapy in hepatocellular carcinoma: from mechanistic insights to clinical translation","authors":"Reza Elahi ,&nbsp;Yassine Alami Idrissi ,&nbsp;Anwaar Saeed","doi":"10.1016/j.ctrv.2025.103046","DOIUrl":"10.1016/j.ctrv.2025.103046","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR)-T cell therapy has transformed cancer immunotherapy, achieving durable complete remissions in hematologic cancers. Yet its translation to solid tumors like hepatocellular carcinoma (HCC), a leading cause of cancer-related deaths worldwide, faces formidable barriers, including immunosuppressive tumor microenvironments (TMEs), antigen heterogeneity, and risks of on-target/off-tumor toxicity. This review discusses the evolving role of CAR-T therapy in HCC across three domains: (1) foundational concepts in CAR-T design, mechanistic action, and antigen-targeting strategies; (2) breakthroughs from preclinical studies and early-phase clinical trials, such as glypican-3 (GPC3) and alpha-fetoprotein (AFP) directed CAR-T cells that have demonstrated preliminary safety and anti-tumor activity; and (3) innovative strategies to overcome TME-driven resistance, including metabolic reprogramming and stromal modulation. We highlight cutting-edge engineering solutions such as armored CAR-T cells engineered for cytokine support, dual-targeting constructs to mitigate antigen escape, and hypoxia-resistant designs alongside synergistic approaches combining CAR-T with immune checkpoint inhibitors or tyrosine kinase inhibitors. Furthermore, we dissect emerging tactics to disrupt TME immunosuppression. While CAR-T therapy holds promise for redefining HCC management, its success will depend on overcoming biological and logistical barriers through patient-tailored designs and robust translational pipelines. Future directions should prioritize biomarker-driven clinical trials, scalable manufacturing platforms, and integration with existing multimodal HCC therapies to maximize durable responses.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103046"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}