The protein defective in the human genetic disorder ataxia-telangiectasia, ATM, plays a central role in responding to DNA double strand breaks and other lesions to protect the genome against DNA damage and in this way minimize the risk of mutations that can lead to abnormal cellular behaviour. Its function in normal cells is to protect the cell against genotoxic stress but inadvertently it can assist cancer cells by providing resistance against chemotherapeutic agents and thus favouring tumour growth and survival. However, it is now evident that ATM also functions in a DNA damage-independent fashion to protect the cell against other forms of stress such as oxidative and nutrient stress and this non-canonical mechanism may also be relevant to cancer susceptibility in individuals who lack a functional ATM gene. Thus the use of ATM inhibitors to combat resistance in tumours may extend beyond a role for this protein in the DNA damage response. Here, we provide some background on ATM and its activation and investigate the efficacy of ATM inhibitors in treating cancer.

中文翻译：

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ATM抑制剂的临床潜力。

人类遗传性疾病共济失调-毛细血管扩张症（ATM）中的蛋白质缺陷在响应DNA双链断裂和其他损伤以保护基因组免受DNA损伤方面起着核心作用，从而将可能导致细胞异常的突变风险降至最低行为。它在正常细胞中的功能是保护细胞免受基因毒性压力，但无意中它可以通过提供对化学治疗剂的抗性来辅助癌细胞，从而有利于肿瘤的生长和存活。但是，现在很明显，ATM还以不依赖DNA损伤的方式发挥功能，以保护细胞免受其他形式的应激，例如氧化应激和营养应激，并且这种非经典机制也可能与缺乏ATM的个体的癌症易感性有关。功能性ATM基因。因此，使用ATM抑制剂来对抗肿瘤中的抗性可能超出了该蛋白质在DNA损伤反应中的作用。在这里，我们提供了一些有关ATM及其激活的背景知识，并研究了ATM抑制剂在治疗癌症中的功效。