The Development of ATM Inhibitors in Cancer Therapy.

IF 4.4 3区 医学 Q2 ONCOLOGY
Elizabeth A Ampolini, Judit Jimenez-Sainz, David T Long
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引用次数: 0

Abstract

The ataxia-telangiectasia mutated (ATM) protein kinase plays a critical role in activating the cellular response to DNA double-strand breaks and promoting homology-directed repair. ATM is frequently mutated in cancer, contributing to an accumulation of DNA damage that drives genomic instability. To exploit cancer cells' inherent vulnerability to DNA damage, various small molecule inhibitors have been developed that target ATM. ATM inhibitors have shown great versatility in preclinical studies and increasing use in the clinic. Here, we review the development of ATM inhibitors and their role in cancer therapy. We describe their limitations and the advances that have led to increases in both the number and diversity of active clinical trials targeting ATM. We also discuss ATM's role in personalized medicine and the current challenges to more widespread use of ATM inhibitors in the clinic.

ATM抑制剂在癌症治疗中的进展。
共济失调毛细血管扩张突变(ATM)蛋白激酶在激活细胞对DNA双链断裂的反应和促进同源性定向修复中起关键作用。ATM在癌症中经常发生突变,导致DNA损伤的积累,从而导致基因组不稳定。为了利用癌细胞对DNA损伤的固有脆弱性,人们开发了各种针对ATM的小分子抑制剂。ATM抑制剂在临床前研究中显示出很大的通用性,并在临床中越来越多地使用。在这里,我们回顾了ATM抑制剂的发展及其在癌症治疗中的作用。我们描述了它们的局限性,以及导致针对ATM的活跃临床试验数量和多样性增加的进展。我们还讨论了ATM在个性化医疗中的作用,以及目前在临床中更广泛使用ATM抑制剂所面临的挑战。
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
Targeted Oncology
Targeted Oncology 医学-肿瘤学
CiteScore
8.40
自引率
3.70%
发文量
64
审稿时长
>12 weeks
期刊介绍: Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes: Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches. Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways. Current Opinion articles that place interesting areas in perspective. Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations. Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement. Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.
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