Signal Transduction and Targeted Therapy最新文献

{"title":"Keeping forks in the loop: how chromatin architecture shields stalled replication forks.","authors":"Nagham Ghaddar, Jessica A Downs","doi":"10.1038/s41392-026-02992-y","DOIUrl":"10.1038/s41392-026-02992-y","url":null,"abstract":"","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"11 1","pages":""},"PeriodicalIF":81.2,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040495","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 biomarker discovery for diseases: diagnostic and therapeutic prospects.","authors":"Rasit Dinc, Nurittin Ardic","doi":"10.1038/s41392-026-02946-4","DOIUrl":"10.1038/s41392-026-02946-4","url":null,"abstract":"<p><p>Biomarkers are central to modern diagnostics and therapeutics, yet traditional discovery approaches suffer from single-modality analyses, weak mechanistic foundations, and low reproducibility. Artificial intelligence (AI) enables the integration of complex multimodal biomedical data, but the translation of AI-derived biomarkers into clinical applications remains inconsistent. This review examines how AI reshapes biomarker discovery across diseases, focusing on biological mechanisms, validation requirements, and therapeutic integration. We synthesize evidence across molecular, cellular, imaging, and digital biomarker approaches, evaluating AI methodologies including classical machine learning, deep learning, graph-based models, foundation models, and causal inference. Findings are organized using a pipeline framework encompassing discovery, external validation, robustness testing, clinical utility, and deployment. AI enables identification of multiscale signatures reflecting cellular programs, tissue remodeling, and disease trajectories. However, many biomarkers fail external validation. Biologically grounded approaches using network-based modeling, spatial profiling, and mechanistic constraints improve interpretability and therapeutic relevance in oncology, cardiovascular disease, neurodegeneration, and metabolic diseases. Validation frameworks with decision curve analysis and prospective evaluation are necessary to demonstrate clinical utility beyond predictive accuracy. AI's impact will depend on integration into rigorous validation and therapeutic pathways. By transitioning from correlational pattern recognition to mechanistically informed, clinically evaluated systems, AI can support next-generation precision diagnostics and targeted interventions.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"11 1","pages":""},"PeriodicalIF":81.2,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040506","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":"RNA therapeutics: current status and future directions.","authors":"Barbara Yang, Melina J Sedano, Karla Perez, Mahalakshmi Vijayaraghavan, Victoria A Reid, Murali M Yallapu, Subhash C Chauhan, Subramanian Dhandayuthapani, Enrique I Ramos, Shrikanth S Gadad","doi":"10.1038/s41392-026-03032-5","DOIUrl":"10.1038/s41392-026-03032-5","url":null,"abstract":"<p><p>RNA-based therapeutics have enabled drug discovery and design by introducing a fundamentally different perspective from conventional therapeutics. RNAs are not only the upstream molecules of proteins (coding) but also functional components of an extensive and intricate regulatory network (noncoding) that helps govern biological processes and mechanisms. Recent advances in functional genomics have accelerated the identification of functional RNAs with well-defined roles and their use in diagnostic and therapeutic approaches, which was previously challenging. RNA molecules can dynamically regulate gene function through their sequence and/or structure. Thus, RNA therapeutics offer distinct strategies for both loss- and gain-of-function interventions. This review focuses on druggable functional RNAs and discusses current and emerging technologies, as well as the scope for their potential clinical utility and targeted treatment. It also highlights the most studied optimization strategies and delivery systems designed to enhance the efficacy and tissue-specific delivery of RNA therapeutics to improve clinical outcomes. Finally, we offer our understanding and perspective on the field. Recent developments in enhancing the stability of these molecules in vivo have further improved the therapeutic potential of RNA-based approaches.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"11 1","pages":""},"PeriodicalIF":81.2,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040476","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":"Inhibition of USP2 suppresses pathological pexophagy and rescues PEX1-deficient peroxisome biogenesis disorder.","authors":"Yong Hwan Kim, Doo Sin Jo, Ae-Kyeong Kim, Kyu Sun Lee, Dong-Hyung Cho","doi":"10.1038/s41392-026-02882-3","DOIUrl":"10.1038/s41392-026-02882-3","url":null,"abstract":"","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"11 1","pages":""},"PeriodicalIF":81.2,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031363","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: Extracellular matrix-derived mechanical force governs breast cancer cell stemness and quiescence transition through integrin-DDR signaling.","authors":"Cong Li, Shi Qiu, Xiaohan Liu, Fengzhu Guo, Jingtong Zhai, Zhijun Li, Linghui Deng, Liming Ge, Haili Qian, Lu Yang, Binghe Xu","doi":"10.1038/s41392-026-03031-6","DOIUrl":"10.1038/s41392-026-03031-6","url":null,"abstract":"","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"11 1","pages":""},"PeriodicalIF":81.2,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040455","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":"Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation","authors":"Cristina Camps-Fajol,Jordi Minguillón,Jordi Surrallés","doi":"10.1038/s41392-026-02954-4","DOIUrl":"https://doi.org/10.1038/s41392-026-02954-4","url":null,"abstract":"","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"89 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149020275","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":"Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets","authors":"Yuan-Yuan Li,Franklin R. Tay","doi":"10.1038/s41392-026-03043-2","DOIUrl":"https://doi.org/10.1038/s41392-026-03043-2","url":null,"abstract":"Abstract Regulated cell death is essential for tissue homeostasis, and its dysregulation contributes to numerous human diseases. Cuproptosis and ferroptosis are metal-dependent forms of regulated cell death distinguished by different biochemical triggers and pathological consequences. Cuproptosis arises from copper-mediated disruption and aggregation of lipoylated mitochondrial proteins, whereas ferroptosis is driven by iron-dependent phospholipid peroxidation. Despite these mechanistic differences, the two pathways intersect through mitochondrial metabolism, redox imbalance, iron–sulfur cluster biology, and organelle crosstalk. Lysosomes, mitochondria, and the endoplasmic reticulum act as critical regulatory hubs that influence cellular susceptibility to both death modalities. This review summarizes current understanding of the molecular mechanisms governing cuproptosis and ferroptosis. It examines the genetic, epigenetic, transcriptional, post-transcriptional, and protein-level networks that regulate these processes. Evidence linking cuproptosis and ferroptosis to cardiovascular, neurodegenerative, autoimmune, metabolic, oral, infectious, and neoplastic diseases is critically evaluated. Therapeutic approaches are discussed, including metal ionophores, chelators, small-molecule modulators, nanomedicine-based delivery systems, and rational combination strategies. Particular attention is given to the context-dependent consequences of activating or suppressing these pathways, and to the challenge of selectively targeting diseased tissues without disrupting systemic metal homeostasis. Successful clinical translation will require reliable biomarkers, mechanistically informed patient stratification, tissue-selective delivery, and a clearer understanding of interactions between metal metabolism, immune responses, and treatment resistance. The review further identifies unresolved questions concerning pathway specificity, temporal regulation, biomarker validation, and the clinical safety of systemic or prolonged therapeutic modulation. Integrating these concepts may enable more precise exploitation of cuproptosis and ferroptosis as therapeutic targets across diverse diseases.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"25 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149020274","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 BIRC6 rejuvenates hematopoietic stem cell aging and immunosenescence","authors":"Weinian Liao,Fangze Shao,Shaoyan Wang,Yetong Wang,Xinliang Chen,Yue Zhang,Zhang Zhang,Xiaodong Zai,Yilong Yang,Ying Yin,Youliang Wang,Jun Zhang,Junping Wang,Junjie Xu","doi":"10.1038/s41392-026-02787-1","DOIUrl":"https://doi.org/10.1038/s41392-026-02787-1","url":null,"abstract":"","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"1 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149020279","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 conjugate engineering: from design to efficacy and safety","authors":"Alberto Ocana,Jorge R. Espinosa,Carlos Alonso-Moreno,Balázs Győrffy,Henry Tong,Atanasio Pandiella","doi":"10.1038/s41392-026-03057-w","DOIUrl":"https://doi.org/10.1038/s41392-026-03057-w","url":null,"abstract":"","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"2 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149020277","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":"Heterogeneity in cancer: molecular mechanisms and therapeutic strategies","authors":"Yong-Lin He,Liang Niu,Yan-ming Ren,Guo-Qiang Yuan,Ya-Wen Pan,Wei-Lin Jin","doi":"10.1038/s41392-026-03064-x","DOIUrl":"https://doi.org/10.1038/s41392-026-03064-x","url":null,"abstract":"","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"397 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149020276","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}