Chemoresistance, radioresistance, and the challenge of achieving complete resection are major driving forces in the search for more robust and targeted anticancer therapies. Targeting the DNA damage response has recently attracted research interest, as these processes are enhanced in tumour cells. The major replication stress responder is ATM and Rad3-related (ATR) kinase, which is attracting attention worldwide with four drug candidates currently in phase I/II clinical trials. This review addresses a potent and selective small-molecule ATR inhibitor, which is known as VX-970 (also known as berzosertib or M6620), and summarizes the existing preclinical data to provide deep insight regarding its real potential. We also outline the transition from preclinical to clinical studies, as well as its relationships with other clinical candidates (AZD6738, VX-803 [M4344], and BAY1895344). The results suggest that VX-970 is indeed a promising anticancer drug that can be used both as monotherapy and in combination with either chemotherapy or radiotherapy strategies. Based on patient anamnesis and biomarker identification, VX-970 could become a valuable tool for oncologists in the fight against cancer.

中文翻译：

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ATR激酶抑制剂berzosertib（VX-970，M6620）的发现：用于癌症治疗的临床候选药物。

化学抗性，放射抗性和实现完全切除的挑战是寻求更强大和针对性的抗癌疗法的主要动力。靶向DNA损伤反应最近引起了研究兴趣，因为这些过程在肿瘤细胞中得到了增强。主要的复制应激反应者是ATM和Rad3相关（ATR）激酶，目前正在I / II期临床试验的四种候选药物引起全球关注。这篇综述针对一种有效的选择性小分子ATR抑制剂，即VX-970（也称为berzosertib或M6620），并总结了现有的临床前数据，以提供有关其实际潜力的深刻见解。我们还将概述从临床前研究到临床研究的转变，以及与其他临床候选者之间的关系（AZD6738，VX-803 [M4344]和BAY1895344）。结果表明，VX-970确实是一种有前途的抗癌药物，既可以用作单一疗法，也可以与化学疗法或放射疗法结合使用。基于患者的回忆和生物标记物识别，VX-970可能成为肿瘤学家抗击癌症的宝贵工具。