共济失调毛细血管扩张突变 (ATM) 激酶在协调 DNA 损伤反应、维持基因组稳定性和调节各种细胞过程中发挥着关键作用。这篇综述对 ATM 的结构、激活机制以及在癌症发生、进展和治疗中的各种功能进行了全面分析。我讨论了 ATM 在某些情况下作为肿瘤抑制因子和癌细胞存活的潜在促进剂的双重性质。本文探讨了 ATM 介导的复杂信号通路、其与其他 DNA 修复机制的相互作用，及其对细胞周期检查点、细胞凋亡和代谢的影响。我研究了 ATM 改变的临床意义，包括它们对癌症易感性、预后和治疗反应的影响。该综述重点介绍了 ATM 靶向治疗的最新进展，讨论了正在进行的 ATM 抑制剂临床试验及其与其他治疗方式结合的潜力。我还解决了开发 ATM 活动有效生物标志物和个性化癌症治疗患者选择策略方面的挑战。最后，我概述了未来的研究方向，强调需要精细的生物标志物开发、优化的联合疗法以及克服潜在耐药机制的策略。这一全面的概述强调了 ATM 在癌症生物学中的至关重要性及其作为精准肿瘤学治疗靶点的新兴潜力。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Ataxia telangiectasia mutated (ATM) kinase plays a pivotal role in orchestrating the DNA damage response, maintaining genomic stability, and regulating various cellular processes. This review provides a comprehensive analysis of ATM's structure, activation mechanisms, and various functions in cancer development, progression, and treatment. I discuss ATM's dual nature as both a tumor suppressor and potential promoter of cancer cell survival in certain contexts. The article explores the complex signaling pathways mediated by ATM, its interactions with other DNA repair mechanisms, and its influence on cell cycle checkpoints, apoptosis, and metabolism. I examine the clinical implications of ATM alterations, including their impact on cancer predisposition, prognosis, and treatment response. The review highlights recent advances in ATM-targeted therapies, discussing ongoing clinical trials of ATM inhibitors and their potential in combination with other treatment modalities. I also address the challenges in developing effective biomarkers for ATM activity and patient selection strategies for personalized cancer therapy. Finally, I outline future research directions, emphasizing the need for refined biomarker development, optimized combination therapies, and strategies to overcome potential resistance mechanisms. This comprehensive overview underscores the critical importance of ATM in cancer biology and its emerging potential as a therapeutic target in precision oncology.Copyright © 2024 The Author. Published by Elsevier Ltd.. All rights reserved.