Veneziani Ana C, Scott Clare, Wakefield Matthew J, Tinker Anna V, Lheureux Stephanie
Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Ther Adv Med Oncol. 2023 Mar 1;15:17588359231157644. doi: 10.1177/17588359231157644. eCollection 2023.
Poly (ADP-ribose) polymerase inhibitors (PARPis) represent a therapeutic milestone in the management of epithelial ovarian cancer. The concept of 'synthetic lethality' is exploited by PARPi in tumors with defects in DNA repair pathways, particularly homologous recombination deficiency. The use of PARPis has been increasing since its approval as maintenance therapy, particularly in the first-line setting. Therefore, resistance to PARPi is an emerging issue in clinical practice. It brings an urgent need to elucidate and identify the mechanisms of PARPi resistance. Ongoing studies address this challenge and investigate potential therapeutic strategies to prevent, overcome, or re-sensitize tumor cells to PARPi. This review aims to summarize the mechanisms of resistance to PARPi, discuss emerging strategies to treat patients post-PARPi progression, and discuss potential biomarkers of resistance.
聚(ADP - 核糖)聚合酶抑制剂(PARPis)是上皮性卵巢癌治疗中的一个里程碑。PARPis利用“合成致死”的概念作用于DNA修复途径存在缺陷,特别是同源重组缺陷的肿瘤。自PARPis被批准作为维持治疗药物以来,其使用量一直在增加,尤其是在一线治疗中。因此,对PARPis的耐药性已成为临床实践中一个新出现的问题。这迫切需要阐明和确定PARPis耐药的机制。正在进行的研究应对这一挑战,并探索预防、克服或使肿瘤细胞对PARPis重新敏感的潜在治疗策略。本综述旨在总结PARPis耐药的机制,讨论PARPis治疗后疾病进展患者的新出现的治疗策略,并探讨潜在的耐药生物标志物。