{"title":"ACK1/TNK2 kinase: molecular mechanisms and emerging cancer therapeutics.","authors":"Dhivya Sridaran, Nupam P Mahajan","doi":"10.1016/j.tips.2024.11.006","DOIUrl":null,"url":null,"abstract":"<p><p>Activated CDC42-associated kinase 1 (ACK1), encoded by the TNK2 gene, is a cytoplasmic non-receptor tyrosine kinase whose aberrant activation correlates positively with cancer severity. Recent research has revealed the functional relevance of this oncokinase - it is an epigenetic regulator that drives cancer progression in multiple malignancies. Although ACK1 is an attractive target for therapeutic intervention, incomplete knowledge of its diverse signaling mechanisms and the lack of specific inhibitors have challenged its clinical success. We summarize recent breakthroughs in understanding ACK1 regulation and cellular signaling, and shed light on its immunomodulatory role in balancing T cell activation. We provide a comprehensive overview of preclinical, proof-of-concept studies of potent ACK1-targeting small-molecule inhibitors that are expected to enter clinical trials for cancer patients.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"62-77"},"PeriodicalIF":13.9000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in pharmacological sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.tips.2024.11.006","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/24 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Activated CDC42-associated kinase 1 (ACK1), encoded by the TNK2 gene, is a cytoplasmic non-receptor tyrosine kinase whose aberrant activation correlates positively with cancer severity. Recent research has revealed the functional relevance of this oncokinase - it is an epigenetic regulator that drives cancer progression in multiple malignancies. Although ACK1 is an attractive target for therapeutic intervention, incomplete knowledge of its diverse signaling mechanisms and the lack of specific inhibitors have challenged its clinical success. We summarize recent breakthroughs in understanding ACK1 regulation and cellular signaling, and shed light on its immunomodulatory role in balancing T cell activation. We provide a comprehensive overview of preclinical, proof-of-concept studies of potent ACK1-targeting small-molecule inhibitors that are expected to enter clinical trials for cancer patients.
期刊介绍：
Trends in Pharmacological Sciences (TIPS) is a monthly peer-reviewed reviews journal that focuses on a wide range of topics in pharmacology, pharmacy, pharmaceutics, and toxicology. Launched in 1979, TIPS publishes concise articles discussing the latest advancements in pharmacology and therapeutics research.
The journal encourages submissions that align with its core themes while also being open to articles on the biopharma regulatory landscape, science policy and regulation, and bioethics.
Each issue of TIPS provides a platform for experts to share their insights and perspectives on the most exciting developments in the field. Through rigorous peer review, the journal ensures the quality and reliability of published articles.
Authors are invited to contribute articles that contribute to the understanding of pharmacology and its applications in various domains. Whether it's exploring innovative drug therapies or discussing the ethical considerations of pharmaceutical research, TIPS provides a valuable resource for researchers, practitioners, and policymakers in the pharmacological sciences.
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