Stephenson Cancer Center, University of Oklahoma HSC, 800 NE 10th St, Suite 5050, Oklahoma City, OK, 73104, USA.
Curr Oncol Rep. 2022 Dec;24(12):1685-1693. doi: 10.1007/s11912-022-01337-6. Epub 2022 Nov 8.
This review will focus on the most common mechanisms for poly (ADP-ribose) polymerase inhibitors' (PARPi) resistance and the main strategies for overcoming acquired or de novo PARPi resistance.
Initial approvals for PARPi as part of treatment for advanced epithelial ovarian cancer (EOC) started in 2014 with patient with recurrent cancer characterized by BRCA mutations in the 3rd and 4th line and now have approvals for front-line maintenance in both the BRCA mutated and BRCAwt populations. As with all therapies, patients will eventually develop resistance to treatment. The most common mechanisms for PARPi resistance include reversion mutations, methylation events, and restoration of homologous recombination deficiency (HRD) through combinations and targeting replication stress. As more and more patients receive initial treatment (and potential retreatment with PARPi), we need to better understand the mechanisms in which tumors acquire PARPi resistance.
本篇综述将聚焦于聚 ADP-核糖聚合酶抑制剂（PARPi）耐药的常见机制，以及克服获得性或新发 PARPi 耐药的主要策略。
PARPi 作为晚期上皮性卵巢癌（EOC）治疗的一部分，于 2014 年首次获批，用于三线及四线治疗具有 BRCA 突变的复发性癌症，目前已批准用于 BRCA 突变和 BRCAwt 人群的一线维持治疗。与所有疗法一样，患者最终将对治疗产生耐药性。PARPi 耐药的最常见机制包括回复突变、甲基化事件，以及通过联合用药和靶向复制应激来恢复同源重组缺陷（HRD）。随着越来越多的患者接受初始治疗（以及潜在的 PARPi 再治疗），我们需要更好地了解肿瘤获得 PARPi 耐药的机制。
