“BRCAness”的概念最初在2004年被描述，用以定义一个肿瘤中同源重组修复（HRR）缺陷与BRCA1或BRCA2失活突变相关，并表现出BRCA1或BRCA2缺陷突变的情况。在发现PARP1/2抑制剂在BRCA1或BRCA2缺陷细胞中具有合成致死性后不久，McCabe和同事通过研究癌细胞对PARP抑制剂的敏感性，将BRCAness的概念扩展到了同源重组缺陷（HRD）。他们从基因上揭示了与HR相关的基因（RAD51，RAD54，DSS1和RPA1），DNA损伤信号基因（ATR，ATM，CHK1，CHK2和NBS1）或Fanconi贫血相关基因（FANCD2，FANCA和FANCC）的缺陷与PARP抑制剂的敏感性有关。因此，细胞通过BRCA或HRD基因的遗传失活获得BRCAness。在这里，我们简要回顾了基因组分析如何识别BRCAness和HRD基因的缺陷以及目前将BRCAness/HRD应用于临床的困难。我们还讨论了BRCAness与HRD的关系以及评估BRCAness/HRD来选择PARP抑制剂（奥拉帕尼布，鲁卡帕尼布，尼拉帕尼布，塔拉佐帕尼布，帕米帕尼布，富祖洛帕尼布），拓扑异构酶I（TOP1）抑制剂（伊立替康，托泊替康和靶向肿瘤TOP1抑制剂）和铂类衍生物（顺铂和卡铂）的疗法的效用。相关文献请参见McCabe等人的文章，《癌症研究》2006年; 66：8109-15.©2023年美国癌症研究协会。

The concept of "BRCAness" was first described in 2004 to define the situation in which a homologous recombination repair (HRR) defect in a tumor relates to and phenocopies BRCA1 or BRCA2 loss-of-function mutations. Soon after the discovery of synthetic lethality of PARP1/2 inhibitors in BRCA1- or BRCA2-deficient cells, McCabe and colleagues extended the concept of BRCAness to homologous recombination deficiency (HRD) by studying the sensitivity of cancer cells to PARP inhibitors. They genetically revealed that deficiency in HR-related genes (RAD51, RAD54, DSS1, and RPA1), DNA damage signaling genes (ATR, ATM, CHK1, CHK2, and NBS1), or Fanconi anemia-related genes (FANCD2, FANCA, and FANCC) conferred sensitivity to PARP inhibitors. Thus, cells acquire BRCAness either by genetic inactivation of the BRCA or HRD genes. Here, we briefly review how genomic profiling can identify BRCAness and deficiencies in HRD genes and the current difficulty to apply BRCAness/HRD in the clinic. We also discuss how BRCAness relates to HRD and the utility of evaluating BRCAness/HRD to select therapies with PARP inhibitors (olaparib, rucaparib, niraparib, talazoparib, pamiparib, fuzuloparib), topoisomerase I (TOP1) inhibitors (irinotecan, topotecan, and tumor-targeted TOP1 inhibitors), and platinum derivatives (cisplatin and carboplatin). See related article by McCabe and colleagues, Cancer Res 2006;66:8109-15.©2023 American Association for Cancer Research.