DNA损伤应答缺陷作为乳腺癌治疗靶点的研究进展

DNA损伤应答（DNA damage response,DDR）缺陷是近年来乳腺癌治疗研究的热门靶点之一。DDR通路负责DNA损伤后的识别、信号转导和修复,其功能异常可导致细胞的凋亡或基因组不稳定性的增加。目前进入临床研究阶段的乳腺癌DDR靶向药物主要包括多聚腺苷二磷酸核糖聚合酶poly (ADP-ribose) polymerase,PARP]抑制剂、ATM抑制剂、CHEK1抑制剂、ATR抑制剂及WEE1抑制剂等。主要从DDR缺陷的概念、以DDR作为靶点的基本原理、DDR各类靶向药物的临床研究现状及其在临床应用中的难点与挑战等方面展开综述。

Targeting DNA damage response deficiency in the treatment of breast cancer

DNA damage response (DDR) deficiency has been one of the emerging targets in treating breast cancer in recent years. The DDR pathway is essential for the identification, signal transduction and repair of DNA damage. Its dysfunction may lead to cell apoptosis or genomic instability. Poly (ADP-ribose) polymerase (PARP) inhibitors, ATM inhibitors, CHEK1 inhibitors, ATR inhibitors and WEE1 inhibitors are DDR drugs that already in the clinical development for treating breast cancer. In this review, we introduced the concept of DDR deficiency, the rationale and research advances in DDR-targeted drugs, and discussed the challenges in its clinical applications.