Investigations of carcinogenesis have evolved from the identification of clonal driver mutations in candidate genes to the integration of large volumes of genomic and transcriptomic data revealing recurrently altered pathways and signatures of mutational processes. Inactivation of BRCA1, BRCA2, or PALB2 impairs efficient double-strand break repair (DSBR), giving rise to a spectrum of homologous recombination deficiency (HRD) cancer phenotypes. Harnessing HRD therapeutically has been promising in a number of tumors; these approaches include leveraging synthetic lethality by targeting alternative repair pathways via PARP inhibition, inducing HRD to modulate potential tumor vulnerabilities, and preventing mechanisms of drug resistance. It is therefore crucial to develop assays for accurate HRD detection and to broaden the patient population who can avail of novel treatment options.

致癌作用的研究已从鉴定候选基因中的克隆驱动基因突变发展到整合了大量的基因组和转录组数据，揭示了反复改变的途径和突变过程的特征。灭活BRCA1，BRCA2或PALB2损害有效的双链断裂修复（DSBR），从而引起一系列同源重组缺陷（HRD）癌症表型。在许多肿瘤中，治疗性利用HRD具有广阔的前景。这些方法包括通过抑制PARP靶向其他修复途径来利用合成杀伤力，诱导HRD调节潜在的肿瘤易感性以及预防耐药性机制。因此，至关重要的是开发能够准确检测HRD的检测方法，并扩大可以利用新颖治疗选择的患者人群。