Li Wenbin, Gao Lin, Yi Xin, Shi Shuangfeng, Huang Jie, Shi Leming, Zhou Xiaoyan, Wu Lingying, Ying Jianming
Department of Pathology, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Geneplus-Shenzhen, Shenzhen 518000, China; Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Genomics Proteomics Bioinformatics. 2023 Oct;21(5):962-975. doi: 10.1016/j.gpb.2023.02.004. Epub 2023 Feb 14.
Defects in genes involved in the DNA damage response cause homologous recombination repair deficiency (HRD). HRD is found in a subgroup of cancer patients for several tumor types, and it has a clinical relevance to cancer prevention and therapies. Accumulating evidence has identified HRD as a biomarker for assessing the therapeutic response of tumor cells to poly(ADP-ribose) polymerase inhibitors and platinum-based chemotherapies. Nevertheless, the biology of HRD is complex, and its applications and the benefits of different HRD biomarker assays are controversial. This is primarily due to inconsistencies in HRD assessments and definitions (gene-level tests, genomic scars, mutational signatures, or a combination of these methods) and difficulties in assessing the contribution of each genomic event. Therefore, we aim to review the biological rationale and clinical evidence of HRD as a biomarker. This review provides a blueprint for the standardization and harmonization of HRD assessments.
参与DNA损伤反应的基因缺陷会导致同源重组修复缺陷（HRD）。在几种肿瘤类型的部分癌症患者中发现了HRD，并且它在癌症预防和治疗方面具有临床相关性。越来越多的证据已将HRD确定为一种生物标志物，用于评估肿瘤细胞对聚（ADP - 核糖）聚合酶抑制剂和铂类化疗的治疗反应。然而，HRD的生物学特性很复杂，其应用以及不同HRD生物标志物检测方法的益处存在争议。这主要是由于HRD评估和定义（基因水平检测、基因组疤痕、突变特征或这些方法的组合）不一致，以及评估每个基因组事件的贡献存在困难。因此，我们旨在综述HRD作为生物标志物的生物学原理和临床证据。本综述为HRD评估的标准化和协调提供了蓝图。
