Targeting the ATM pathway in cancer: Opportunities, challenges and personalized therapeutic strategies

IF 11.3 1区化学 Q1 CHEMISTRY, PHYSICAL ACS Catalysis Pub Date : 2024-08-05 DOI:10.1016/j.ctrv.2024.102808

Ji-Hoon Lee

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Abstract

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.

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瞄准癌症中的 ATM 通路：机遇、挑战和个性化治疗策略。

共济失调毛细血管扩张症突变（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。这篇综述全面分析了 ATM 的结构、激活机制以及在癌症发生、发展和治疗中的各种功能。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潜在促进因子的双重性质。文章探讨了 ATM 介导的复杂信号通路、它与其他 DNA 修复机制的相互作用，以及它对细胞周期检查点、细胞凋亡和新陈代谢的影响。我探讨了ATM改变的临床意义，包括其对癌症易感性、预后和治疗反应的影响。综述重点介绍了ATM靶向疗法的最新进展，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联合应用的潜力。我还探讨了开发有效的 ATM 活性生物标记物和个性化癌症治疗患者选择策略所面临的挑战。最后，我概述了未来的研究方向，强调需要完善生物标志物的开发、优化联合疗法以及克服潜在耐药机制的策略。这篇全面的综述强调了 ATM 在癌症生物学中的关键重要性及其作为精准肿瘤学治疗靶点的新兴潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Catalysis CHEMISTRY, PHYSICAL-

CiteScore

20.80

自引率

6.20%

发文量

1253

审稿时长

1.5 months

期刊介绍： ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels. The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.