Molecular Cancer最新文献

{"title":"Correction: Multi‑omics analysis identifies different molecular subtypes with unique outcomes in early-stage poorly differentiated lung adenocarcinoma.","authors":"Bing Liu, Wei Tao, Xuantong Zhou, Li-Di Xu, Yanrui Luo, Xin Yang, Qingjie Min, Miao Huang, Yuge Zhu, Xinrun Cui, Yaqi Wang, Tongyang Gong, Enli Zhang, Yu S Huang, Weizhi Chen, Shi Yan, Nan Wu","doi":"10.1186/s12943-026-02802-7","DOIUrl":"10.1186/s12943-026-02802-7","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002329","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":"Genotype-driven tumor ecosystems drive immune evasion and immunotherapy resistance in melanoma.","authors":"Milad Ibrahim, Irineu Illa-Bochaca, Tara Muijlwijk, Ines Delclaux, Katherine S Ventre, George Jour, Paola Angulo Salgado, Shi Qiu, Agrima Dutt, Amanda W Lund, Iman Osman, Markus Schober","doi":"10.1186/s12943-026-02781-9","DOIUrl":"10.1186/s12943-026-02781-9","url":null,"abstract":"<p><strong>Background: </strong>Genetic and transcriptional alterations in cancer cells shape their interactions with immune and stromal compartments, thereby influencing tumor progression, immune evasion, and response to immune checkpoint inhibitors (ICIs). Yet, how these interactions are spatially organized within melanoma and how they relate to clinical outcome remains incompletely understood.</p><p><strong>Methods: </strong>We used spatial multi-omic profiling on melanoma tissues from patients, compared those with loss-of-function mutations in the Neurofibromin 1 (NF1) tumor suppressor gene to those with intact NF1, and integrated these results with functional studies and subsequent gene expression changes observed in patient-derived melanoma models and an immunotherapy-resistant syngeneic mouse model.</p><p><strong>Results: </strong>Spatial multi-omic analysis of melanoma tissues from patients identified 12 meta-niches composed of distinct cell populations with unique molecular features. Although all tumors contained these meta-niches, those enriched in immunosuppressive cancer-associated fibroblasts (CAFs) and macrophages were significantly more common in tumors with NF1 loss. Conversely, niches enriched in cytotoxic CD8⁺ T cells were significantly reduced. In both human and mouse melanoma, NF1 loss was associated with impaired antigen-presentation programs and reduced CD8⁺ T cell infiltration. Mechanistically, EGFR signaling emerged as a prominent feature of NF1-deficient melanoma ecosystems and correlated with reduced expression of antigen-presentation genes and T cell exclusion. EGFR inhibition restored the expression of antigen-presentation programs and enhanced antitumor immune responses in a syngeneic Nf1 knockdown model resistant to ICIs.</p><p><strong>Conclusions: </strong>These findings define spatially organized, functionally distinct meta-niches enriched in NF1-mutant melanoma that may contribute to their aggressive disease features and poor ICI response. Our study links an understudied melanoma driver to specific immune-evasion mechanisms and identifies EGFR inhibition as a candidate strategy to improve outcomes in patients with NF1-mutant melanoma resistant to immunotherapy.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149062823","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":"KMT9 drives T cell exclusion and dysfunction by promoting PMN-MDSCs infiltration and ARG1 expression in prostate cancer.","authors":"Jon Peñarando, Dominica Willmann, Manuela Sum, Yanhan Jia, Christopher Berlin, Lukas M Braun, Zihao Chen, Sylvia Urban, Manfred Jung, Delphine Duteil, Daniel Metzger, Christian Gratzke, Robert Zeiser, Holger Greschik, Roland Schüle, Eric Metzger","doi":"10.1186/s12943-026-02801-8","DOIUrl":"10.1186/s12943-026-02801-8","url":null,"abstract":"<p><p>Immunotherapy has emerged as a revolutionary therapeutic approach to treat cancer showing remarkable clinical responses. However, its efficacy in solid tumours such as prostate cancer (PCa) remains very limited due to a highly immunosuppressive tumour immune microenvironment (TIME) that hampers cytotoxic T cell infiltration and activity. Here, we show that lysine methyltransferase 9 (KMT9) governs the formation of an immunosuppressive TIME in PCa. KMT9 regulates the expression of tumour-secreted myeloid-attracting C-X-C motif chemokine receptor 2 (CXCR2) ligands such as C-X-C motif chemokine ligand 5 (CXCL5) thereby promoting the infiltration of immunosuppressive polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) within tumours. These changes collectively result in decreased activation and exclusion of cytotoxic T cells from tumour glands. Furthermore, we demonstrate that KMT9 confers tumour cell-resistance to T cell cytotoxicity by regulating expression of arginase 1 (ARG1). Accordingly, KMT9α ablation results in inhibition of prostate tumour growth accompanied by a massive reduction of PMN-MDSC recruitment and a significant increase in cytotoxic T cell activation and infiltration of the prostate tumour glands. Together, we uncovered KMT9 as a regulator of immune evasion that promotes an immune-excluded TIME in prostate tumours. Furthermore, our findings establish KMT9 as a therapeutic target to reprogram the immunosuppressive landscape and potentially improve the clinical efficacy of current immunotherapies.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002366","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":"Extrachromosomal DNA as a platform for epigenetic reprogramming in cancer.","authors":"Bi-Xia Liu, Lu Zhou, Shuzhen Lai, Xueqiong Han, Xi-Jian Dai, Rui Liu, Yuxin Wang, Daosong Chen, Jialiang Wei, Hongkang Hu, Wenhan Zu, Lei Jiang, Jin Chang, Lisha Zha","doi":"10.1186/s12943-026-02789-1","DOIUrl":"https://doi.org/10.1186/s12943-026-02789-1","url":null,"abstract":"<p><p>Extrachromosomal DNA (ecDNA) has emerged as a major contributor to cancer aggressiveness, yet its role extends far beyond its classical definition as a vehicle for oncogene amplification. Recent studies indicate that ecDNA functions as a dynamic regulatory platform that reshapes chromatin accessibility, enhancer activity, three-dimensional genome organization, nuclear architecture, and transcriptional output. Through these properties, ecDNA enables cancer cells to amplify oncogenic signaling, generate transcriptional plasticity, and rapidly adapt to selective pressures. In contrast to chromosomal amplification, ecDNA is structurally independent, frequently circular, acentromeric, and inherited through noncanonical mitotic behaviors, allowing unequal segregation, coordinated co-inheritance, and persistent propagation of advantageous regulatory states. Emerging evidence further shows that ecDNA can hijack pre-existing enhancers, rewire enhancer-oncogene communication, activate noncanonical regulatory elements, and assemble into transcriptionally active nuclear hubs and condensate-associated structures, thereby transforming genome rearrangement into epigenetic innovation. These mechanisms position ecDNA as a key driver of intratumoral heterogeneity, clonal evolution, metastatic adaptation, and therapeutic resistance. At the same time, the high transcriptional burden and specialized regulatory architecture of ecDNA-positive tumors may create selective vulnerabilities, including transcription-replication conflict and dependence on ecDNA-associated hubs, condensates, and regulatory modules. In this review, we synthesize current advances in the formation, regulation, inheritance, and functional consequences of ecDNA, with a particular focus on its emerging role as a platform for epigenetic reprogramming in cancer. We also discuss how this conceptual shift from copy-number biology to regulatory biology may redefine ecDNA as both a mechanistic framework for tumor plasticity and a potential frontier for precision oncology.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112470","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":"KIF11 inhibition remodels lineage state and sensitizes castration-resistant prostate cancer to antiandrogen therapy via enhancer–promoter looping","authors":"Zihao Deng,Lifang He,Jiayi Li,Sile She,Xi Luo,Jiediao Lin,Zhaochang Qi,Yixuan Zhuang,Xinya Gao,Zepai Chi,Zhe Xu,Yandan Ji,Jing Liu,Stanley Li Lin,Yukun Cui","doi":"10.1186/s12943-026-02792-6","DOIUrl":"https://doi.org/10.1186/s12943-026-02792-6","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"70 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922920","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":"Identification of novel paracrine therapeutic targets in peritoneal metastases through integrative proteotranscriptomic analysis of ascites","authors":"Ying Liu,Clara Yieh Lin Chong,Yingrui Wang,Luang Xu,Hui Jun Lim,Qiu Xuan Tan,Josephine Hendrikson,Joey Wee-Shan Tan,Gillian Ng,Wanyu Guo,Youming Wang,Lingling Huang,Weigang Ge,Vinoth Kumar Rethineswaran,Jolynn Zu Lin Ong,Ying En Quek,Andre Jing Yuen Ang,Fionicca Teo,Oris Wanyi Chen,Ananya Rajesh,Yuwei Zhang,Tun Kiat Ko,Bavani Kannan,Boon Yee Lim,Elizabeth Chun Yong Lee,Zexi Guo,Vairavan Lakshmanan,Nicholas Brian Shannon,Nagalakshmi Jegannathan,Craig Ryan Joseph,Zhen Wei Neo,Li Yen Chong,Amanda R. H. Ng,Jia-Ying Joey Lee,Lit-Hsin Loo,Yang Wu,Siyu Zhang,Lanqi Nie,Qiqi Zhang,Lei Zeng,Tony Kiat Hon Lim,Matthew Chau Hsien Ng,Christabel Jing Zhi Lee,Pik Eu Jason Chang,Kevin Kim-Jun Teh,Hiang Keat Tan,Ravichandran Nadarajah,Tze Tein Yong,Junjie Wang,Ieera Madan Aggarwal,Eliza Li Shan Fong,Kenny Zhuoran Wu,Jimmy Bok Yan So,Khay Guan Yeoh,Jolene Si Min Wong,Chin Jin Seo,Mingzhe Cai,Claramae Shulyn Chia,Bin Tean Teh,Iain Beehuat Tan,Joe Yeong,Jason Yongsheng Chan,Tiannan Guo,Chin-Ann Johnny Ong,Singapore Peritoneal Oncology Study (SPOS) Group and Singapore Gastric Cancer Consortium (SGCC)","doi":"10.1186/s12943-026-02787-3","DOIUrl":"https://doi.org/10.1186/s12943-026-02787-3","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"39 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922921","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":"Extracellular vesicle–enriched SPP1 programs MMP11⁺ fibroblast states to drive immune exclusion in lung adenocarcinoma","authors":"Xiaotian He,Lijian Qian,Dechang Zhao,Gongming Wang,Xuewen Zhang,Yisheng Ye,Lei Li,Yingsheng Wen,Lanjun Zhang","doi":"10.1186/s12943-026-02785-5","DOIUrl":"https://doi.org/10.1186/s12943-026-02785-5","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"11 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922925","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":"The abscopal effect and systemic immune reprogramming: from phenomenon to therapeutic design","authors":"Zhipeng Hong,Zhicheng Huang,Aozi Feng,Fangchao Zhao,Junjie Kuang,Zhihao Lei,Yupeng Sha,Jingyuan Shao,Ayan Kumar Barui,Raghvendra Mall,Jun Zhao,Bing Yang,Yundong Zhou,Debo Chen,Quan Yuan","doi":"10.1186/s12943-026-02794-4","DOIUrl":"https://doi.org/10.1186/s12943-026-02794-4","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"35 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922922","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":"UQCRC2 lactylation-mediated mitophagy orchestrates colorectal cancer cell metabolism to establish a drug-tolerant state during chemotherapy","authors":"Shuohui Dong,Qian Xu,Mingguang Zhang,Shuo Liang,Xiang Zhao,Li Luo,Linchuan Li,Zitian Liu,Guangwei Yang,Ao Yu,Lei Chen,Qian Liu,Sanyuan Hu,Guangyong Zhang","doi":"10.1186/s12943-026-02793-5","DOIUrl":"https://doi.org/10.1186/s12943-026-02793-5","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"7 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922924","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":"Nanomedicines for resistant tumours in the central nervous system: novel materials and mechanisms of action","authors":"Guixiong Li,Yau-Tuen Chan,Feiyu Xiong,Youhai Xin,Runsen Hong,Zeyu Xie,Wen Zhou,Cheng Zhang,Ruihao Zhang,Ning Wang,Qinguo Huang","doi":"10.1186/s12943-026-02783-7","DOIUrl":"https://doi.org/10.1186/s12943-026-02783-7","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"17 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922923","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}