Signal Transduction and Targeted Therapy最新文献_第8页

Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets 铜下垂和铁下垂：信号通路、疾病和治疗靶点

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2026-09-23 DOI: 10.1038/s41392-026-03043-2

Yuan-Yuan Li,Franklin R. Tay

{"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}

引用次数: 0

Targeting BIRC6 rejuvenates hematopoietic stem cell aging and immunosenescence 靶向BIRC6使造血干细胞衰老和免疫衰老恢复活力

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2026-09-23 DOI: 10.1038/s41392-026-02787-1

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

引用次数: 0

Antibody-drug conjugate engineering: from design to efficacy and safety 抗体-药物偶联工程：从设计到疗效和安全性

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2026-09-23 DOI: 10.1038/s41392-026-03057-w

Alberto Ocana,Jorge R. Espinosa,Carlos Alonso-Moreno,Balázs Győrffy,Henry Tong,Atanasio Pandiella

引用次数: 0

Heterogeneity in cancer: molecular mechanisms and therapeutic strategies 癌症的异质性：分子机制和治疗策略

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2026-09-23 DOI: 10.1038/s41392-026-03064-x

Yong-Lin He,Liang Niu,Yan-ming Ren,Guo-Qiang Yuan,Ya-Wen Pan,Wei-Lin Jin

引用次数: 0

Retinoic acid in health and disease 维甲酸在健康和疾病中的作用

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2026-09-22 DOI: 10.1038/s41392-026-03055-y

Maria Teresa De Angelis,Vincenzo Dattilo,Niccolò Vono,Valentina Lise,Michela Reda,Carmela De Marco,Antonia Rizzuto,Francesco Trapasso,Giuseppe Viglietto,Gianluca Santamaria

引用次数: 0

Cell death: immunogenic potential of cuproptosis in cancer. 细胞死亡：癌症中铜增生的免疫原性潜能。

IF 81.2 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2026-09-22 DOI: 10.1038/s41392-026-02974-0

Lorenzo Galluzzi, Oliver Kepp, Guido Kroemer

引用次数: 0

Fracture healing: from molecular and cellular mechanisms to therapeutic strategies. 骨折愈合：从分子和细胞机制到治疗策略。

IF 81.2 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2026-09-22 DOI: 10.1038/s41392-026-02967-z

Flurina Staubli, Renske Maria Tariro Ten Ham, Jan Eelco Bergsma, Debby Gawlitta, Kenny Man

{"title":"Fracture healing: from molecular and cellular mechanisms to therapeutic strategies.","authors":"Flurina Staubli, Renske Maria Tariro Ten Ham, Jan Eelco Bergsma, Debby Gawlitta, Kenny Man","doi":"10.1038/s41392-026-02967-z","DOIUrl":"10.1038/s41392-026-02967-z","url":null,"abstract":"Fracture healing is a highly orchestrated regenerative process that depends on precise temporal and spatial coordination of immune, vascular, neural, and skeletal signaling programs. Disruption of these interconnected pathways, whether due to local injury factors, systemic disease, aging, or metabolic dysregulation, can impair repair and result in delayed union or nonunion. Understanding the molecular mechanisms that integrate inflammation resolution, progenitor cell fate decisions, neurovascular coupling, and endochondral bone formation is therefore essential for improving clinical outcomes. Recent advances show that fracture repair is governed by dynamic signaling networks linking immune cells, mesenchymal progenitors, endothelial and neural components, and the extracellular matrix. Key pathways regulating cytokine signaling, angiogenesis, mechanotransduction, hypoxia sensing, and osteochondral differentiation have emerged as critical determinants of healing efficiency and quality. These insights have reshaped therapeutic strategies, enabling the development of targeted interventions, including growth factor and anabolic therapies, immunomodulatory agents, cell- and gene-based approaches, extracellular vesicles, and biomaterial-assisted delivery systems. In this review, we synthesize current mechanistic understanding of both physiological and impaired fracture healing, with an emphasis on intercellular signaling and pathway-level regulation. We critically evaluate emerging targeted regenerative therapies in terms of their biological rationale, precision, and translational limitations, and discuss key barriers to clinical implementation. By shifting focus from descriptive pathology to actionable signaling frameworks, this review aims to guide the rational design of next-generation therapies for bone regeneration.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"11 1","pages":""},"PeriodicalIF":81.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13594354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018106","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}

引用次数: 0

Inhibition of CDK/Cyclin-phospho-Rb signaling by amebaciclib may have an antitumor effect against uterine leiomyosarcoma 阿米巴昔单抗抑制CDK/Cyclin-phospho-Rb信号通路可能对子宫平滑肌肉瘤具有抗肿瘤作用

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2026-09-21 DOI: 10.1038/s41392-026-02983-z

Takuma Hayashi, Manabu Muto, Ikuo Konishi

引用次数: 0

Correction: Extracellular vesicle-based drug overview: research landscape, quality control and nonclinical evaluation strategies. 修正：基于细胞外囊泡的药物概述：研究前景、质量控制和非临床评价策略。

IF 81.2 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2026-09-21 DOI: 10.1038/s41392-026-02999-5

Gangling Xu, Jing Jin, Zhihao Fu, Guangming Wang, Xinhua Lei, Jun Xu, Junzhi Wang

引用次数: 0

Breast cancer-associated fibroblast-derived exosomal miR-1290 promotes triple-negative breast cancer cell proliferation. 乳腺癌相关成纤维细胞来源的外泌体miR-1290促进三阴性乳腺癌细胞增殖。

IF 81.2 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2026-09-20 DOI: 10.1038/s41392-026-02922-y

Jinkwon Lee, Taesang Son, Gyeonghwa Kim, Hye Won Lee, In Hwan Tae, Yunsang Kang, Jeongmin Lee, Jinsan Kim, Su-Gi Lee, Tae-Hee Han, Hyun Seung Ban, Kunhyang Park, Cho-Rok Jung, Jung Hwa Lim, Mi-Young Son, Dae-Soo Kim, Keun Hur, Tae-Su Han, Hyun-Soo Cho

{"title":"Breast cancer-associated fibroblast-derived exosomal miR-1290 promotes triple-negative breast cancer cell proliferation.","authors":"Jinkwon Lee, Taesang Son, Gyeonghwa Kim, Hye Won Lee, In Hwan Tae, Yunsang Kang, Jeongmin Lee, Jinsan Kim, Su-Gi Lee, Tae-Hee Han, Hyun Seung Ban, Kunhyang Park, Cho-Rok Jung, Jung Hwa Lim, Mi-Young Son, Dae-Soo Kim, Keun Hur, Tae-Su Han, Hyun-Soo Cho","doi":"10.1038/s41392-026-02922-y","DOIUrl":"10.1038/s41392-026-02922-y","url":null,"abstract":"Breast cancer is a major cause of cancer-associated mortality in females. Although therapeutic strategies targeting subtype-specific receptors have been developed for various breast cancer subtypes, effective targeted therapies for triple-negative breast cancer (TNBC) are lacking. Recently, the role of the tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), in the progression and metastasis of breast cancer, especially TNBC, has attracted increasing attention. However, the role of exosomes secreted by CAFs in TNBC cell proliferation is poorly understood. Thus, in this study, we analyzed exosomes derived from both CAFs and MDA-MB-231 cells and identified exosomal miR-1290 as a key component. When delivered to TNBC cells (BT-549 and Hs578T), exosomal miR-1290 directly suppressed the expression of the putative tumor suppressor TBC1D4, which was accompanied by reduced TSC1 expression and activation of the mTOR pathway. The promotion of TNBC cell growth by miR-1290 through direct targeting of TBC1D4 was validated using 2D culture models, 3D spheroid models, and in vivo xenograft models. Furthermore, we demonstrated that treatment with the mTOR inhibitor rapamycin and the FDA-approved rapamycin analog everolimus effectively suppressed miR-1290-induced TNBC cell proliferation, suggesting a potential therapeutic strategy for TNBC. Moreover, in patient cohorts, elevated levels of circulating miR-1290 significantly distinguished patients with breast cancer from healthy individuals and correlated with poor survival outcomes. Therefore, miR-1290 and its direct target TBC1D4 have potential value in both targeted treatment and diagnosis of TNBC.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"11 1","pages":""},"PeriodicalIF":81.2,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040512","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}

引用次数: 0