Molecular Cancer最新文献

{"title":"Liquid-liquid phase separation in cancer radiotherapy and immunotherapy: emerging roles and translational opportunities","authors":"Chenchen Dong,Cong Shang,Bing Han,Ziyi Liu,Jiaoyang Wang,Peng Cao,Juan Zeng,Ayao Guo,Xiufang Ren,Shuo Cao","doi":"10.1186/s12943-026-02813-4","DOIUrl":"https://doi.org/10.1186/s12943-026-02813-4","url":null,"abstract":"Abstract Liquid-liquid phase separation (LLPS) is a physicochemical process through which biomolecules assemble into membraneless condensates via weak, multivalent interactions. LLPS has emerged as a central biological principle that helps explain intracellular spatiotemporal compartmentalization, signal transduction, and stress responses. Dysregulated LLPS contributes to tumor initiation, progression, immune evasion, and treatment resistance; however, its cell-type-specific functions and relevance to radiotherapy and immunotherapy remain incompletely integrated. In this review, we critically synthesize recent mechanistic and translational advances linking LLPS to cancer radiotherapy and immunotherapy. Condensates may either support therapeutic resistance and immune evasion or enhance radiosensitivity and antitumor immunity, depending on their molecular composition, subcellular localization, cell type, and treatment context. We examine how condensate regulation connects radiation-induced DNA damage repair with innate immune activation and evaluate emerging therapeutic strategies that target disease-associated condensates. We also assess LLPS-associated abnormal condensates as candidate biomarkers for prognosis and prediction of tumor response to radiotherapy and immunotherapy. Tissue-specific LLPS regulation across tumor types, dynamic condensate remodeling under therapeutic stress, and rational strategies combining phase-separation modulation with immune-checkpoint inhibitors and radiotherapy require further investigation. Integrating multi-omics data with artificial intelligence-based algorithms may help construct systematic LLPS-related therapeutic-event maps and predictive models, thereby prioritizing experimentally testable hypotheses for personalized cancer management. With rigorous mechanistic validation and prospective clinical evaluation, selective modulation of disease-associated condensates may enhance radiosensitivity and strengthen antitumor immunity.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"22 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208508","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":"circRAB6A-encoded KAPEP relieves PTPN6-mediated restraint on JAK-STAT signaling to drive KRAS-mutant colorectal cancer progression","authors":"Haitao Yuan,Jiaxin Lin,Kexin Chen,Hongming Li,Liaonan Zou,Xinquan Lu","doi":"10.1186/s12943-026-02818-z","DOIUrl":"https://doi.org/10.1186/s12943-026-02818-z","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"13 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208507","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":"Tumor-associated CALD1 splicing variant driven by hnRNPA1 promotes colorectal cancer metastasis","authors":"Jin Wang,Hulin Ma,Wenrong Liu,Qingbin Wu,Ying Lu,Yue Ming,Jiawei Guo,Jiao Li,Lunzhi Dai,Ting-Hua Wang,Jinlin Yang,Yong Peng","doi":"10.1186/s12943-026-02812-5","DOIUrl":"https://doi.org/10.1186/s12943-026-02812-5","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"4 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208506","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 PD-1/PD-L1 axis in cancer: from immune evasion mechanisms to next-generation therapeutics","authors":"Le-Le Zhang,Yi Wang,Yuqi Fu,Hongyao Li,Xuelan Ma,Mu-Yang Huang,Zhenghai Tang,Jiang-Jiang Qin,Ting Li","doi":"10.1186/s12943-026-02790-8","DOIUrl":"https://doi.org/10.1186/s12943-026-02790-8","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"31 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208509","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":"Antibody-drug conjugates: mechanism, progress and future directions of cancer targeted therapy","authors":"Manshan Li,Geyan Wu,Bingfeng Chen,Zhongyu Zheng,Xiaoxue Ning,Jun Li,De Zeng,Jie Li,Junwei Song","doi":"10.1186/s12943-026-02817-0","DOIUrl":"https://doi.org/10.1186/s12943-026-02817-0","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"7 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208510","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":"It takes two to tango: the intersection of deubiquitinases and m⁶A modification in cancer.","authors":"Xuan Zhang, Ning Lou, Yudan Wang, Haolong Li, Chuyan Nie, Yongzhe Li, Xiaohong Han","doi":"10.1186/s12943-026-02808-1","DOIUrl":"10.1186/s12943-026-02808-1","url":null,"abstract":"<p><p>The dynamic and reversible N⁶-methyladenosine (m⁶A) RNA modification has emerged as a pivotal layer of epitranscriptomic regulation in cancer, governing RNA metabolism and function. Concurrently, deubiquitylating enzymes (DUBs), key components of the post-translational modifications (PTMs) system, orchestrate protein stability and signaling pathways crucial for tumorigenesis. Recent evidence reveals extensive and intricate crosstalk between these two regulatory systems, forming a complex network that can influence cancer progression. This review systematically explores the bidirectional interplay between DUBs and m⁶A modification. On one hand, specific DUBs can deubiquitinate and stabilize core m⁶A \"writers\" (methyltransferases), \"erasers\" (demethylases), or \"readers\" (recognition proteins), thereby influencing RNA metabolism and downstream gene expression. On the other hand, m⁶A modification can regulate the expression of certain DUBs, either by influencing the stability and translation of their mRNAs or by controlling associated regulatory factors. This reciprocal regulation profoundly impacts key oncogenic processes, including cell proliferation, metastasis, metabolic reprogramming, and therapy resistance. By integrating current findings, this review highlights the significance of the DUB-m⁶A axis as a critical regulatory hub in cancer biology. Deciphering this crosstalk not only provides novel insights into tumor mechanisms but also unveils promising therapeutic targets for overcoming drug resistance and developing innovative anti-cancer strategies.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":42.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195101","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":"Mechanism-guided drug repurposing against therapeutically actionable resistance domains in cancer: from resistance biology to clinical translation","authors":"Haowen Zhang,Xinyuan Zhu,Yixuan Tao,Siyuan Luan,Xin Xiao,Xiaokun Li,Jichun Shao,Jianfeng Zhou,Yong Yuan","doi":"10.1186/s12943-026-02815-2","DOIUrl":"https://doi.org/10.1186/s12943-026-02815-2","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"13 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208512","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":"Targeting TEAD in cancers: paralog-specific biology, resistance and therapeutic opportunities","authors":"Jialin Wu,Fuda Xie,Bonan Chen,Tiejun Feng,Muyang Huang,Terry Cheuk-Fung Yip,Yang Lyu,Peiyao Yu,Zichen Zhao,Bingying Luo,Jun Yu,Ka Fai To,Dazhi Xu,Wei Kang","doi":"10.1186/s12943-026-02809-0","DOIUrl":"https://doi.org/10.1186/s12943-026-02809-0","url":null,"abstract":"Abstract The TEA domain transcription factors TEAD1 to TEAD4 integrate Hippo signaling with transcriptional programs that govern tissue homeostasis and cancer progression. Their activity is shaped by cofactor engagement, palmitoylation, chromatin organization and extracellular cues, creating therapeutic vulnerabilities that vary with tumor lineage and cellular state. This review examines TEAD molecular architecture, physiological functions and paralog-specific biology, together with canonical regulation by NF2/Merlin and the Hippo kinase cascade and non-canonical inputs from mechanical cues, oncogenic signaling, metabolism and hypoxia. Particular attention is given to the distinct interactions of YAP1 and TAZ with TEAD and the contribution of alternative cofactors to transcriptional output. Across cancer types, the evidence distinguishes tumors with strong YAP1/TAZ-TEAD dependence, exemplified by NF2-deficient mesothelioma, from settings in which the pathway supports tumor plasticity, immune evasion and treatment resistance or may restrain tumor growth. These differences emphasize that TEAD expression or pathway activation alone does not establish functional dependence or reliably predict therapeutic response. Therapeutic approaches include TEAD lipid pocket inhibitors, disruptors of YAP1/TAZ-TEAD interactions, degraders, cofactor-switching compounds and YAP1-directed oligonucleotides. Early clinical findings with VT3989 in mesothelioma support the therapeutic potential of TEAD inhibition, while highlighting unresolved questions concerning patient selection, durability of benefit and renal tolerability. Priorities for clinical development include functional biomarkers of TEAD dependence, pharmacodynamic confirmation of target engagement and combinations guided by defined resistance mechanisms. Progress will depend on translating these mechanistic insights into durable antitumor efficacy at tolerable exposures in appropriately selected patients.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"162 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210495","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":"Oncogenic KRAS drives immune evasion through adenosine metabolic reprogramming mediated by NT5E and ADA","authors":"Jing Yuan,Wenwen Ding,Yuhong Zhang,Rui Liu,Jing Yang,Wenhua Lu,Bitao Huo,Qiao Liu,Xiaoying Wei,Paul J. Chiao,Christophe Glorieux,Shijun Wen,Christophe Nicot,Panpan Liu,Peng Huang","doi":"10.1186/s12943-026-02810-7","DOIUrl":"https://doi.org/10.1186/s12943-026-02810-7","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"97 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208511","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":"Intratumoral microbiota: spatiotemporal dynamics, microenvironmental immune reprogramming, and immunotherapeutic implications","authors":"Zhiyong Xiang,Weishi Cheng,Yijun Wu,Ting Niu,Ailin Zhao,Kai Kang","doi":"10.1186/s12943-026-02811-6","DOIUrl":"https://doi.org/10.1186/s12943-026-02811-6","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"8 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150068","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}