Clinical & Translational Oncology最新文献

{"title":"Artificial intelligence in pancreatic cancer: applications in early detection, tumor staging, and survival prediction-a comprehensive review.","authors":"Nilambar Sethi, Chekuri Vinod Varma, Shiva Shankar Reddy","doi":"10.1007/s12094-026-04381-x","DOIUrl":"10.1007/s12094-026-04381-x","url":null,"abstract":"<p><p>In the rapidly developing world, artificial intelligence (AI) is one of the emerging applications in the medical domain. Early detection of cancer is one of the most difficult processes, especially when it comes to the differentiation of cancer's structure, length, and size. AI methodology offers innovations and decision-making applicable to specific processes like data collecting, management, results, and conclusions. Due to the lack of particular indicators, the difficult location of the pancreas, and the absence of early symptoms, pancreatic cancer (PC) is difficult to identify with low and late analysis. However, the imaging approach is slightly improving analysis, but there is still potential for enhancement in systematizing guidelines. This comprehensive review will mainly focus on various applications of AI in pancreatic cancer diagnosis. Furthermore, this review presents various architectures based on machine learning (ML) and deep learning (DL) methods for applications such as early detection, classification, tumor staging, and pancreatic cancer survival prediction. In order to better comprehend challenging cases, clinical practitioners can benefit from the supplementary information and useful recommendations provided by various techniques. Finally, this review potentially analyzes the advantages and drawbacks present in pancreatic cancer. This review provides an overview of research based on AI methods and algorithms that provide superior performance from a variety of pancreatic cancer patients while also providing viable future perspectives with significant advancements to overcome drawbacks in previous research and provide enhanced performance, stating their effectiveness and robustness analysis.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4308-4327"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147935112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression and diagnostic significance of plasma exosomal RNA in diffuse large B-cell lymphoma.","authors":"Xiaomei Ma, Zimiao Zhang, Jiayi Deng, Yueyuan Lai, Aili Zhang, Congjie Chen, Xiaohui Shangguan, Weihao Wu, Longtian Chen","doi":"10.1007/s12094-026-04336-2","DOIUrl":"10.1007/s12094-026-04336-2","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the expression profiles of plasma exosomal RNAs in patients with Diffuse Large B-Cell Lymphoma (DLBCL) and evaluate their diagnostic potential.</p><p><strong>Methods: </strong>Exosomes were isolated from 9 DLBCL patients and 9 healthy controls, followed by whole transcriptome RNA sequencing to identify differentially expressed RNAs. Key RNAs were selected and validated via qRT-PCR using an independent cohort of 41 treatment-naïve DLBCL patients and 41 healthy controls. The StarBase database was utilized to predict target relationships and construct lncRNA/miRNA competing endogenous RNA (ceRNA) pairs. Diagnostic efficacy was assessed using Receiver Operating Characteristic (ROC) curve analysis.</p><p><strong>Results: </strong>High-throughput sequencing revealed significant RNA expression differences between DLBCL patients and healthy controls. Specifically, 35 microRNAs (miRNAs), 1604 long non-coding RNAs (lncRNAs), and 330 messenger RNAs (mRNAs) were differentially expressed in the DLBCL group, while no significant differences were observed in circular RNA (circRNA) expression. Two ceRNA pairs, MALAT1/hsa-miR-181a-5p and SLC9A3-AS1/hsa-miR-10a-5p, were constructed. qRT-PCR validation confirmed that hsa-miR-181a-5p and hsa-miR-10a-5p were significantly down-regulated, while SLC9A3-AS1 was up-regulated in the DLBCL group; MALAT1 expression showed no significant difference. ROC analysis demonstrated Area Under the Curve (AUC) values of 0.813 for hsa-miR-181a-5p, 0.800 for hsa-miR-10a-5p, and 0.787 for SLC9A3-AS1. The combined AUC for SLC9A3-AS1 and hsa-miR-10a-5p was 0.8226, and for SLC9A3-AS1 and hsa-miR-181a-5p was 0.852.</p><p><strong>Conclusion: </strong>Exosome-derived miRNAs, lncRNAs, and mRNAs exhibit distinct expression patterns in DLBCL patients compared to healthy controls. The RNAs hsa-miR-181a-5p, hsa-miR-10a-5p, and SLC9A3-AS1 show promise as diagnostic biomarkers for DLBCL, with combined RNA panels offering improved diagnostic efficacy over single markers. The SLC9A3-AS1/hsa-miR-10a-5p pair may form a regulatory network influencing DLBCL pathogenesis.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4892-4902"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world characterization of PD-L1 expression in patients with advanced esophagogastric adenocarcinoma in Spain.","authors":"Paula Jimenez-Fonseca, Marc Diez Garcia, Juan Luis Catoya-Villa, Pablo Pérez-Wert, Laura Visa, Alberto Carmona-Bayonas, María Luisa Limón, Ana Fernández-Montes, Margarita Reboredo, Rosario Vidal-Tocino, Javier Gallego Plazas, Guillermo Eduardo Mendoza, Stefania Landolfi, Ana Teijo, Laura Guerra-Pastrian, Andrés Nieto, Jose Luis Domínguez-Miranda, María Luisa López-Vega, Marta Rodríguez-Gonzalez, Francisco José Illán-Gambín, Eva Martínez de Castro, Cinta Hierro, Mireia Gil-Raga, María Robles González, María Elena Moreno Gutiérrez, David Vilanova, Mar Iglesias-Coma","doi":"10.1007/s12094-026-04343-3","DOIUrl":"10.1007/s12094-026-04343-3","url":null,"abstract":"<p><strong>Purpose: </strong>Epidemiological data from Sapin are lacking, especially in a publication relating Spanish data and prevalence of programmed cell death ligand-1 (PD-L1) expression. This study aimed to evaluate the prevalence of PD-L1 expression by Combined Positive Score (CPS) ≥ 5 in patients with advanced esophagogastric adenocarcinoma (aEGAC) in Spain.</p><p><strong>Methods: </strong>This observational, retrospective, and multicenter study collected sociodemographic and clinical data from adult patients with locally advanced unresectable, recurrent, or metastatic EGAC across 21 centers in the AGAMENON-SEOM registry. CPS PD-L1 expression was centrally analyzed using the IHC 28-8 pharmDx.</p><p><strong>Results: </strong>A total of 166 patients were included, with 144 valid and evaluable samples. The primary tumor locations were stomach (70.1%), gastroesophageal junction (19.4%), and esophagus (10.4%). At diagnosis, 84.0% had synchronous metastatic disease, 4.9% had unresectable locally advanced disease, and 11.1% had recurrent disease. PD-L1 CPS ≥ 5 was observed in 41.7% of the patients (95%CI, 34.3-50.4%). Prevalence by tumor type was 41.6% (95% CI, 32.0-51.2%) in gastric adenocarcinoma, 35.7% (95% CI, 18.0-53.5%) in gastroesophageal junction adenocarcinomas, and 60.0% (95% CI, 35.2-84.8%) in esophageal adenocarcinoma. PD-L1 CPS ≥ 5 was found in 42.9% (95% CI, 6.2-79.5%) of patients with unresectable locally advanced disease, 43.0% (95% CI, 34.2-51.8%) of those with metastatic disease, and 37.5% (95% CI, 13.8-61.2%) of those with recurrent disease.</p><p><strong>Conclusion: </strong>This is the first study to report the real-world prevalence of PD-L1 expression in patients with aEGAC in clinical practice in Spain. These findings underscore the importance of understanding PD-L1 prevalence in the Spanish population and investigating discrepancies with previous studies.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4728-4737"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-138-5p inhibits WiT-49 cell growth in vitro by downregulating TCF3 expression, and suppresses tumorigenesis in vivo.","authors":"Zhigang Yao, Nian Zhou, Huangchenghao Zhang, Cuilian Li, Hongchao Jiang, Zipeng Hao, Bing Yan, Hui Zhao","doi":"10.1007/s12094-026-04373-x","DOIUrl":"10.1007/s12094-026-04373-x","url":null,"abstract":"<p><strong>Purpose: </strong>miR-138-5p plays a tumor-suppressing role, but its function in Wilms tumor (WT) has not yet been explored. This study aimed to investigate the role of miR-138-5p in the progression of WT.</p><p><strong>Methods: </strong>Hematoxylin‒eosin staining was used to analyze histopathological changes in WT tissues and adjacent normal tissues. qPCR was used to detect the expression of miR-138-5p in WT tissues and cells. Immunohistochemical staining and qPCR were used to detect the expression of TCF3. The interaction between miR-138-5p and TCF3 was confirmed by correlation analysis, qPCR, and dual-luciferase assays, respectively. CCK-8, colony formation, Transwell, and wound-healing assays were performed to identify the effects of miR-138-5p and TCF3 on the proliferation and migration of WiT49 cells. A murine xenograft model was used to investigate the function of miR-138-5p on WT growth in vivo.</p><p><strong>Results: </strong>miR-138-5p was expressed at low levels in WT tissues and WiT-49 cells. Functional studies demonstrated that the upregulation of miR-138-5p markedly inhibited the proliferation, colony-formation capacity, and migratory/invasive potential of WiT-49 cells. Subsequently, the therapeutic potential of miR-138-5p overexpression was confirmed in murine xenograft models, which markedly inhibited tumor growth compared with that in the control group. TCF3 is a target of miR-138-5p, and its expression is negatively correlated with that of miR-138-5p. Furthermore, the results of rescue experiments indicated that the tumor-suppressing effects of miR-138-5p in WiT-49 cells were reversed by TCF3 overexpression.</p><p><strong>Conclusions: </strong>miR-138-5p could be a tumor suppressor that regulates the proliferation of WT cells by targeting and reducing TCF3 expression.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4915-4926"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HER2 discordance between primary and metastatic gastric cancer: a systematic review and meta-analysis.","authors":"Francisco Cezar Aquino Moraes, Luis Henrique Rios Moreira Rego, Thiago Gorayeb Rebelo, Gustavo Tadeu Freitas Uchôa Matheus, Ana C Melo","doi":"10.1007/s12094-026-04359-9","DOIUrl":"10.1007/s12094-026-04359-9","url":null,"abstract":"<p><strong>Purpose: </strong>Gastric cancer (GC) remains a major global health burden, with poor survival rates. HER2 is a key biomarker for targeted therapy, but discordance between primary tumors and metastases may impact treatment decisions. This meta-analysis evaluated the prevalence and clinical relevance of HER2 status differences between primary gastric cancers and metastatic lesions.</p><p><strong>Methods: </strong>A systematic search of PubMed, Embase, and Cochrane was conducted for studies assessing HER2 status in matched primary and metastatic gastric cancer samples. Pooled proportions and 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses by metastatic site were performed. Statistical analyses were conducted using R software, version 4.2.3.</p><p><strong>Results: </strong>This meta-analysis included 3,515 patients across 20 studies. The pooled proportion of HER2-positive expression in primary gastric tumors was 13% (95% CI: 12-15%; I² = 68.7%), while HER2-negative tumors accounted for 74% (95% CI: 72%-76%; I² = 94.9%). In metastatic sites, the overall pooled proportion of HER2-positive lesions was 18% (95% CI: 16%-20%; I² = 77.3%), with notable variation across anatomical locations: 38% in lung metastases, 31% in liver metastases, 19% in lymph nodes, and 7% in peritoneum. Conversely, HER2-negative metastases accounted for 82% overall (95% CI: 80%-84%; I² = 78.2%), with proportions of 93% in peritoneum, 81% lymph nodes, 69% in liver metastases, and 62% in lung.</p><p><strong>Conclusions: </strong>Significant heterogeneity in HER2 expression between primary and metastatic gastric cancer underscores the need for reassessment of HER2 status in metastatic sites. Relying solely on primary tumor samples may lead to underestimation of HER2 positivity and suboptimal therapeutic decisions. Incorporating site-specific HER2 testing into clinical practice may enhance patient selection for HER2-targeted therapies and improve treatment outcomes.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4738-4748"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147876608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic landscape and clinicopathological predictors of survival in gallbladder cancer.","authors":"Manoj Pandey, Monika Rajput, Satya Vijay Chigurupati, Madhumita Tripathi","doi":"10.1007/s12094-026-04355-z","DOIUrl":"10.1007/s12094-026-04355-z","url":null,"abstract":"<p><strong>Background: </strong>Gallbladder cancer (GBC) is highly aggressive with a disproportionate incidence in North India. This study integrates clinicopathological and genomic profiles to identify drivers of mortality and recurrence in a regional cohort.</p><p><strong>Methods: </strong>Retrospective analysis was conducted on 35 GBC patients using targeted Next-Generation Sequencing (NGS). Survival analysis (OS and DFS) and Cox regression identified independent prognostic factors using Python-based pipelines.</p><p><strong>Results: </strong>The cohort showed a 97% mortality rate and a 7-month median survival. At diagnosis, 80% presented with advanced disease (Stages III-IV). Somatic mutations occurred in 60% of patients, primarily TP53 (31.4%) and KRAS (14.3%). While mutation status did not significantly impact OS (p = 0.8974), multivariable Cox regression identified elevated CA19-9 (p = 0.028) and age > 40 years (p = 0.009) as independent mortality predictors. In the DFS model, KRAS mutation demonstrated a strong trend toward higher recurrence risk (HR = 7.54, p = 0.064).</p><p><strong>Conclusion: </strong>High mortality and poor survival in North Indian GBC are driven by late-stage presentation. While CA19-9 and age are robust mortality predictors, KRAS mutations signify rapid recurrence. These findings emphasize the need for localized genomic screening to guide precision oncology in high-burden populations.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4749-4757"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking mucinous colorectal adenocarcinoma classification: evidence from histopathology and RAS mutations.","authors":"Dorra Wider, Haifa Tounsi Guettiti, Monia Ardhaoui, Amira Jaballah-Gabteni, Jihenne Ben Aissa, Ines Ben Ayed, Nadia Ben Jemii, Hamza Yaiche, Emna Fehri, Essia Habachi, Afifa Maaloul, Emna Ennaifer, Samir Boubaker","doi":"10.1007/s12094-026-04269-w","DOIUrl":"10.1007/s12094-026-04269-w","url":null,"abstract":"<p><strong>Purpose: </strong>Mucinous adenocarcinoma (MAC) is a distinct and aggressive subtype of colorectal cancer (CRC), traditionally defined by > 50% mucinous component. However, evidence suggests tumors with lower mucin content may behave similarly. This study investigated clinicopathological and molecular differences between mucinous and non-mucinous CRC, and evaluated the prognostic relevance of the current mucin threshold.</p><p><strong>Methods: </strong>We retrospectively analyzed 1716 CRC cases (2017-2021) from the Institut Pasteur de Tunis. Tumors were classified as NMAC (0-5% mucin), ACMC1 (5-50%), or MAC (> 50%). .RAS mutation status was determined using Lightmix (TibMolBiol). Clinical, histological, and metastatic features comparison across groups and survival analysis were assessed using SPSS v26.</p><p><strong>Results: </strong>Tumors with any mucinous component (5-100%) were significantly associated with right-sided location (p < 0.001), signet-ring cells (p < 0.001), synchronous peritoneal metastasis (p = 0.002-0.02), and KRAS mutations (p = 0.031) versus NMAC. Importantly, ACMC1 (5-50%) shared aggressive features with MAC, including lymphovascular invasion (p = 0.027) and distinct metastatic patterns.</p><p><strong>Conclusions: </strong>Our findings debate the WHO 50% mucin threshold, showing that tumors with 5-50% mucin exhibit comparable aggressiveness to classical MAC. Integrating molecular profiling with histology may improve risk stratification and guide tailored therapeutic strategies for mucinous CRC, regardless of mucin proportion.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4781-4793"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in the regulation of CD47 by non-coding RNAs and its therapeutic potential in cancer.","authors":"Jingwen Hua, Weijin Zhu, Xiaochun Sun, Huabiao Chen","doi":"10.1007/s12094-026-04380-y","DOIUrl":"10.1007/s12094-026-04380-y","url":null,"abstract":"<p><p>Cluster of Differentiation 47 (CD47) is regarded as a highly promising next-generation immunotherapy target following PD-1/PD-L1. It mediates tumor immune escape by transmitting a \"don't eat me\" signal through the signal regulatory protein alpha (SIRPα) pathway. However, the clinical application of existing antibody therapies remains constrained by erythrocyte toxicity, the antigen sink caused by widespread CD47 expression on normal cells, and recent setbacks in clinical trials. \"Growing evidence establishes non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), as key upstream regulators of CD47. Here, we systematically review how these ncRNAs control CD47 gene expression, focusing on their impact on phagocytosis, drug resistance, and tumor microenvironment remodeling. Unlike antibody-mediated blockade, targeting the ncRNA-CD47 axis provides a unique avenue for genetic modulation, offering reduced systemic toxicity. We summarize these regulatory mechanisms and explore how exploiting these gene-regulatory networks can address the current challenges in CD47 immunotherapy.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4511-4532"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expert consensus on optimal management of liver-related adverse events during CDK4/6 inhibitor therapy.","authors":"Sonia Pernas, Xavier Forns, Olga Martínez-Sáez, Raúl Andrade, Alberto Amador, Elena López-Miranda, Begoña Bermejo, Beatriz Mateos, Monica Cejuela, María José Villanueva, Patricia Palacios Ozores, Mar Riveiro-Barciela, Meritxell Bellet","doi":"10.1007/s12094-026-04369-7","DOIUrl":"10.1007/s12094-026-04369-7","url":null,"abstract":"<p><p>Hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR + /HER2 -) breast cancer (BC) is the most frequently diagnosed subtype of BC, accounting for approximately 70% of cases. The introduction of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) has significantly improved clinical outcomes and transformed the therapeutic landscape of HR + /HER2 - in both the metastatic and early settings.Hepatotoxicity associated with CDK4/6i is increasingly recognized as a clinically relevant adverse event. Most cases are asymptomatic, occur early during treatment, and resolve with dose modification or management according to the Summary of Product Characteristics (SmPC). However, variability in monitoring and management persists in clinical practice. Key issues, such as corticosteroid use, treatment continuation and reintroduction of the CDK4/6i (either the same compound or another among the three globally approved agents) after liver toxicity recovery, remain insufficiently addressed by current evidence, despite the need for routine clinical decision-making.To address these gaps, a Spanish multidisciplinary panel of hepatologists and medical oncologists developed expert consensus recommendations on liver toxicity in patients with HR + /HER2 - BC receiving CDK4/6i. This consensus provides practical guidance on the classification, monitoring and management of liver-related adverse events during CDK4/6i therapy and promotes proactive collaboration between oncology and hepatology teams to support treatment continuity and optimize patient outcomes.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4546-4559"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147870331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming T cell exhaustion and senescence in CAR T cell therapy for solid tumors.","authors":"Ignacio Pérez-Criado, Mariona Figols, Ainhoa Moya-Sevilla, Ana Bautista, Daniela Gómez-Díaz, Albert Font, Juan Martin-Liberal, Vicenç Ruiz de Porras","doi":"10.1007/s12094-026-04383-9","DOIUrl":"10.1007/s12094-026-04383-9","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cell therapies have demonstrated remarkable efficacy in hematologic malignancies; however, their clinical benefit in solid tumors remains limited. A major barrier is T cell dysfunction, particularly exhaustion and senescence, which impair persistence, effector function, and durable tumor control. Targeting these dysfunctional states is therefore essential in order to improve CAR T cell efficacy in solid tumors.This review summarizes recent preclinical strategies aimed at preventing or reversing CAR T cell exhaustion and senescence in solid malignancies. While both exhaustion and senescence are relevant dysfunctional states, the preclinical evidence summarized in this review is currently more extensive for modulation of exhaustion-associated programs than for direct reversal of canonical T cell senescence. Approaches are organized according to their primary mechanistic focus, including gene editing, metabolic modulation, receptor redesign, and remodeling of the tumor microenvironment.Across these mechanistic categories, reported benefits include enhanced CAR T cell persistence, reduced expression of inhibitory receptors, such as PD-1, LAG-3, and TIM-3, preservation or restoration of memory-like phenotypes, and improved antitumor cytotoxicity. Notably, combinatorial strategies targeting multiple dysfunction pathways consistently demonstrate superior efficacy in preclinical models. Despite these advances, important translational challenges remain, including the limited predictive value of current preclinical systems, potential safety concerns, and the manufacturing complexity associated with increasingly engineered cell products.Collectively, preclinical evidence supports the rational integration of complementary approaches to generate next-generation CAR T cells capable of resisting dysfunction and maintaining activity within immunosuppressive solid tumor microenvironments. Further validation in clinically relevant models will be critical to facilitate translation into safe and durable cancer immunotherapies.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4533-4545"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}