同源重组修复缺陷与乳腺癌研究回顾及评述

摘 要：合成致死是一种新型抗肿瘤方式，基于该理论开发的第一款DNA损伤药物PARP抑制剂与同源重组修复缺陷（homologous recombination repair deficiency，HRD）形成合成致死作用，在卵巢癌、前列腺癌中显示出突破性疗效。HRD形成除了与乳腺癌遗传易感基因BRCA1/2突变有关外，还与其他同源重组修复蛋白功能的缺失有关。目前主要通过基因组瘢痕分析来评估肿瘤HRD状态。在乳腺癌中，HRD是重要的分子标志，然而相关研究进展缓慢，限制了其在乳腺癌临床实践中的应用。全文介绍HRD的形成机制、检测方法及其在乳腺癌中的研究进展及其困境，以期为乳腺癌的临床诊疗与研究设计提供新思路。

Comments on Homologous Recombination Repair Deficiency in Breast Cancer

Abstract： Synthetic lethality is a new method of anti-tumor therapy. PARP inhibitor is the first DNA damage drug designed on this theory， which gives rise to synthetic lethality effect combined with homologous recombination repair deficiency (HRD)， and has demonstrated significant efficacy in ovarian cancer and prostate cancer. The formation of HRD is related to the mutation of BRCA1/2， and the function loss of other homologous recombinant repair proteins. At present， the status of tumor HRD is mainly evaluated by genomic scar analysis. In breast cancer， HRD is an important molecular marker， however， the slow progress of related research has limited its clinical application. This comment introduces the formation mechanism， detection methods， research progress and difficulties of HRD in breast cancer， to provide new ideas for clinical diagnosis， treatment and research design of breast cancer.