Molecular Cancer最新文献

{"title":"Immune-pressure redistribution in resistance to PD-1/PD-L1 blockade: mechanisms, biomarkers, and therapeutic design","authors":"Xiaodong Wang, Jiayi Liu, Alifujiang Hairulajiang, Junjie Wang, Qianqian Wang, ZhiHong Li, Bingwen Zou, Yeqian Feng","doi":"10.1186/s12943-026-02786-4","DOIUrl":"https://doi.org/10.1186/s12943-026-02786-4","url":null,"abstract":"PD-1/PD-L1 blockade can produce durable tumor control, yet primary, adaptive, and acquired resistance remain common. Existing accounts often catalogue resistance by cellular compartment, obscuring the coordinated nature of tumor adaptation. Here, we introduce immune-pressure redistribution as a treatment-oriented framework that complements cancer immunoediting by asking where therapeutic immune pressure is diverted after checkpoint release. Resistance is organized into three coupled routes: transfer into tumor-intrinsic escape through antigen-presentation loss, interferon-response defects, oncogenic rewiring, and lineage plasticity; weakening through defective priming, terminal T-cell differentiation, compensatory checkpoints, metabolic constraint, and chronic cytokine signaling; and unloading into stromal, vascular, myeloid, regulatory, microbial, and systemic host compartments. We integrate clinically validated mechanisms with emerging evidence, including the temporal duality of interferon–JAK signaling, the role of tumor-draining lymph nodes in sustaining progenitor-exhausted T cells, and the limited translation of TIGIT, IDO1, TGF-β, and CSF-1R targeting. We further propose a biomarker-guided strategy that combines tumor visibility, immune-cell state, spatial architecture, systemic inflammation, and early treatment dynamics to identify the dominant resistance topology. This framework supports topology-matched combinations and adaptive sequencing rather than uniform escalation, with the aim of restoring productive immune pressure while limiting compensatory escape and toxicity.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"19 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003648","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":"mRNA therapeutics in cancer: from molecular design to clinical translation","authors":"Zhixiong Zhu,Jia Li,Hexian Li,Qizhong Lu,Zhengyu Yu","doi":"10.1186/s12943-026-02796-2","DOIUrl":"https://doi.org/10.1186/s12943-026-02796-2","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"58 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922926","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":"T cell receptors equipped with ICOS provide T cells with durable anti-tumor response","authors":"Alexandre Marraffa,Cor Berrevoets,Margherita Mosiello,Rui M.L. Coelho,Daphne Roelofs,Mandy van Brakel,Rebecca Wijers,Kim Kroese,Marlies J.W. Peeters,Willem A. Dik,Andre Kunert,Rachel J.M. Abbott,Dora Hammerl,Christopher Schliehe,Reno Debets","doi":"10.1186/s12943-026-02765-9","DOIUrl":"https://doi.org/10.1186/s12943-026-02765-9","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"11 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922927","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":"Correction: METTL3 facilitates tumor progression via an m6A-IGF2BP2-dependent mechanism in colorectal carcinoma","authors":"Ting Li,Pei-Shan Hu,Zhixiang Zuo,Jin-Fei Lin,Xingyang Li,Qi-Nian Wu,Zhan-Hong Chen,Zhao-Lei Zeng,Feng Wang,Jian Zheng,Demeng Chen,Bo Li,Tie-Bang Kang,Dan Xie,Dongxin Lin,Huai-Qiang Ju,Rui-Hua Xu","doi":"10.1186/s12943-026-02780-w","DOIUrl":"https://doi.org/10.1186/s12943-026-02780-w","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"27 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893796","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":"Correction: Multimodal sequencing identifies synergistic mechanisms driving resistance to neoadjuvant nivolumab treatment in hepatocellular carcinoma.","authors":"Fanhong Zeng, Jiaxin Guo, Zheng Zeng, Vanilla Xin Zhang, Yu-Man Tsui, Po-Man Li, Abdullah Husain, Qingyang Zhang, Joyce Man-Fong Lee, Tan-To Cheung, Daniel Wai-Hung Ho, Irene Oi-Lin Ng","doi":"10.1186/s12943-026-02777-5","DOIUrl":"10.1186/s12943-026-02777-5","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Human epididymis protein 4 in association with Annexin II promotes invasion and metastasis of ovarian cancer cells.","authors":"Huiyu Zhuang, Mingzi Tan, Juanjuan Liu, Zhenhua Hu, Dawo Liu, Jian Gao, Liancheng Zhu, Bei Lin","doi":"10.1186/s12943-026-02779-3","DOIUrl":"10.1186/s12943-026-02779-3","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep molecular profiling of lung neuroendocrine tumours and supra-carcinoids.","authors":"Alexandra Sexton-Oates, Émilie Mathian, Noah Candeli, Yuliya Lim, Catherine Voegele, Alex Di Genova, Laurane Mangé, Zhaozhi Li, Tijmen van Weert, Lipika Kalson, Tiffany M Delhomme, Lisa M Hillen, Ricardo Blázquez-Encinas, Abel Gonzalez-Perez, Maike L Morrison, Eleonora Lauricella, Lise Mangiante, Lisa Bonheme, Laura Moonen, Gudrun Absenger, Janine Altmuller, Cyril Degletagne, Odd Terje Brustugun, Vincent Cahais, Giovanni Centonze, Amélie Chabrier, Cyrille Cuenin, Francesca Damiola, Vincent Thomas de Montpréville, Jean-François Deleuze, Anne-Marie C Dingemans, Élie Fadel, Nicolas Gadot, Akram Ghantous, Paolo Graziano, Paul Hofman, Véronique Hofman, Alejandro Ibáñez-Costa, Stéphanie Lacomme, Nuria Lopez-Bigas, Marius Lund-Iversen, Massimo Milione, Lucia Anna Muscarella, Sergio Pedraza-Arevalo, Corinne Perrin, Gaetane Planchard, Helmut Popper, Luca Roz, Angelo Sparaneo, Wieneke Buikhuisen, José van den Berg, Margot Tesselaar, Jaehee Kim, Ernst Jan M Speel, Séverine Tabone-Eglinger, Thomas Walter, Gavin M Wright, Justo P Castaño, Lara Chalabreysse, Liming Chen, Christophe Caux, Marco Volante, Nicolas Girard, Jean-Michel Vignaud, Esther Conde, Audrey Mansuet-Lupo, Luka Brcic, Giuseppe Pelosi, Mauro Giulio Papotti, Sylvie Lantuejoul, Jules Derks, Talya Dayton, Nicolas Alcala, Matthieu Foll, Lynnette Fernandez-Cuesta","doi":"10.1186/s12943-026-02721-7","DOIUrl":"10.1186/s12943-026-02721-7","url":null,"abstract":"<p><strong>Background: </strong>Lung neuroendocrine tumours (NETs, also known as carcinoids) are rapidly rising in incidence worldwide but have unknown aetiology and limited therapeutic options beyond surgery. The current WHO classification, based on mitotic count and presence or absence of necrosis, divides lung NETs into grade-1 typical, and grade-2 atypical tumours. This dichotomous classification however does not account for recently described molecular entities nor is it sufficient for clinical management.</p><p><strong>Methods: </strong>Here we conducted integrative multi-omic analyses on over 300 lung NETs including whole-genome sequencing, transcriptome profiling, and DNA methylation arrays, followed by archetype analysis, to identify and characterise molecular groups. We further investigated molecular groups using spatial RNA sequencing and proteomics, and deep learning analysis of whole slide images.</p><p><strong>Results: </strong>The integration of multi-omic data provided definitive proof of the existence of four strikingly different molecular groups that vary in patient characteristics, genomic and transcriptomic profiles, microenvironment, and morphology. Among these, we identified a new molecular group, enriched for highly aggressive supra-carcinoids that displayed an immune-rich microenvironment linked to tumour-macrophage crosstalk. We uncovered an undifferentiated cell population within supra-carcinoids and show the transcriptomic similarities between supra-carcinoids and the recently identified atypical small cell lung cancer tumours, further demonstrating their molecular link to high-grade lung neuroendocrine carcinomas. Multi-regional genomic analyses identified distinct evolutionary trajectories, suggesting that molecular groups are determined early in tumourigenesis by genomic events, and that transitions between groups, though infrequent, are possible for supra-carcinoids. Deep learning models accurately identified these groups based on morphology alone, outperforming current histological criteria. Together with the validation of a panel of immunohistochemistry markers, we demonstrated that these molecular groups can be accurately identified based on morphological features, facilitating their future implementation in the clinical setting. Our proposed morpho-molecular classification highlights potential group-specific therapeutic opportunities, with differences in expression to DLL3, EGFR, FGFR and TERT inhibitor targets.</p><p><strong>Conclusions: </strong>Overall, our findings unify previously proposed molecular classifications and refine the lung cancer map by revealing novel tumour phenotypes with potential implications for prognosis and therapeutic management.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A targetable dependency on nonsense-mediated decay for cellular homeostasis and immune control in small cell lung cancer.","authors":"Lucia A Torres-Fernández, Volker Boehm, Joel Kaufmann, Jonas P Becker, Maria Garcia-Marquez, Beaunelle de Bruijn, Agnieszka Rumińska, Christian Müller, Graziella Bosco, Nazanin Alavinejad, Laura Lovric, Johanna I Bihler, Hanna Schulte, Poorya Davoodi, Anna Schöllhorn, Kian R Weihrauch, Laura Kaiser, Olta Ibruli, Fanyu Liu, Ariadne Androulidaki, Nina Wobst, Marcel Schmiel, Justinas Valiulis, Lukas Maas, Joshua D'Rozario, Vignesh Sakthivelu, Bianca Göbel, Marian Touet, Johannes Brägelmann, Katja Höpker, Felix John, Jürgen Wolf, Stefan Knapp, Alexander Quaas, Maria Cartolano, Silvia von Karstedt, Filippo Beleggia, Hans-Georg Rammensee, Cécile Gouttefangeas, Hans A Schlößer, Angelika B Riemer, Hans Christian Reinhardt, Niels H Gehring, Martin Peifer, Roman K Thomas, Julie George","doi":"10.1186/s12943-026-02750-2","DOIUrl":"10.1186/s12943-026-02750-2","url":null,"abstract":"<p><p>Small cell lung cancer (SCLC) is one of the most aggressive malignancies, characterized by rapid metastatic dissemination and poor overall survival. Despite harboring excessive alterations, expectedly resulting in immunogenic neoantigens, patients with SCLC remain largely refractory to immunotherapy. We found abundant frameshift mutations in SCLC, regarded as highly immunogenic, counterbalanced by a hyperactive nonsense-mediated decay (NMD) pathway, responsible for frameshift-mRNA degradation. NMD activity correlated with tumor mutational burden (TMB) across cancers, suggesting that SCLC and other TMB^high cancers may depend on NMD to limit the accumulation of mutation-derived byproducts in order to maintain cellular homeostasis and evade immune recognition. In TMB^high SCLC models, inhibition of NMD impaired cell proliferation and induced ER stress-dependent apoptosis due to the accumulation of misfolded proteins. Genetic and pharmacological NMD inhibition in vivo effectively controlled TMB^high tumor growth without overt toxicity. By integrating genome and transcriptome sequencing with MHC-I immunopeptidomics and functional in vitro and in vivo assays, we identified that NMD inhibition boosted neoantigen expression and presentation by tumor cells and increased T cell recognition, thus enhancing overall tumor immunogenicity and further improving immunotherapy efficacy in vivo. Our work shows that SCLC - as a TMB^high cancer - relies on NMD for survival and immune escape, uncovering a novel TMB-dependent tractable vulnerability for this devastating disease.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Novel lncRNA-IUR suppresses Bcr-Abl-induced tumorigenesis through regulation of STAT5-CD71 pathway.","authors":"Xuefei Wang, Jianling Yang, Guijie Guo, Riyue Feng, Ke Chen, Yuan Liao, Lianfeng Zhang, Liping Sun, Shile Huang, Ji-Long Chen","doi":"10.1186/s12943-026-02776-6","DOIUrl":"10.1186/s12943-026-02776-6","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence in oncology: linking biological discovery to clinical utility.","authors":"Sai Kiran Kuchana, Nikhilesh V Alahari, Rohith Kode, Karishma R Jalapu, Suresh K Alahari","doi":"10.1186/s12943-026-02771-x","DOIUrl":"https://doi.org/10.1186/s12943-026-02771-x","url":null,"abstract":"<p><strong>Background: </strong>Artificial intelligence (AI) has expanded rapidly across the oncology continuum-spanning early detection, histopathology, molecular profiling, treatment selection, drug discovery, toxicity surveillance, and survivorship care. However, these varied applications occupy fundamentally different stages of clinical and biological translation.</p><p><strong>Methods: </strong>We conducted a critical narrative review searching PubMed/MEDLINE, Europe PMC, IEEE Xplore, arXiv, and ClinicalTrials.gov (updated to July 21, 2026). From these sources, an evidence map of 202 publications (including 182 original studies) was assembled based on study design, prospective or external validation, mechanistic rigor, clinical utility, and representation across the cancer continuum.</p><p><strong>Results: </strong>The primary synthesis demonstrates evidence gradient rather than uniform translation across oncology: Detection & Imaging: Select mammography and colonoscopy tools are supported by randomized controlled trials demonstrating workflow efficiency and detection gains. Conversely, negative pragmatic trials highlight that robust technical accuracy does not automatically translate into improved diagnostic pathways.</p><p><strong>Pathology: </strong>Large self-supervised and vision-language foundational models exhibit strong cross-task and cross-institutional transferability. However, prospective real-world deployment remains rare, and reporting on calibration, subgroup performance, and data provenance is inconsistent. Molecular & Systems Biology: Multi-omics, single-cell, spatial transcriptomics, graph-based, and perturbation models increasingly yield falsifiable hypotheses regarding tumor microenvironments, regulatory networks, and drug vulnerabilities; most, however, lack upstream functional validation. Therapeutic Decision Support: Applications in treatment response, surgical assistance, toxicity monitoring, and clinical large language models (LLMs) remain limited by cohort heterogeneity, temporal drift, unstandardized endpoints, and a lack of evidence that model-guided care alters patient outcomes.</p><p><strong>Conclusion: </strong>AI applications must be evaluated using evidence matched directly to their specific clinical or biological claims: external validation for transportability, calibration/decision analysis for utility, prospective workflow studies for operational value, randomized trials for patient outcome benefits, and perturbation experiments for biological mechanism. This claim-matched framework clarifies the boundary between promising computational models and clinically or mechanistically credible oncology, establishing a roadmap for reliable integration into precision cancer care.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}