Centre Léon Bérard, Lyon, France; University Claude Bernard Lyon 1, France.
Department of Gynecology & Gynecologic Oncology, Ev. Kliniken Essen-Mitte, Essen, Germany.
Cancer Treat Rev. 2021 Sep;99:102255. doi: 10.1016/j.ctrv.2021.102255. Epub 2021 Jul 15.
Poly-(ADP)-ribose polymerase inhibitors (PARPi) are a class of oral anticancer drugs first developed as "synthetically lethal" in cancers harboring BRCA1/BRCA2 inactivating mutations. In high-grade serous or endometrioid ovarian cancers (HGOC), PARPi demonstrated benefit as maintenance therapy in relapsing BRCA-mutated and non-mutated tumors. Recently, they extended their indications to frontline maintenance therapy. This review summarizes the current place of PARPi (i) as maintenance or single agent in recurrent disease and (ii) frontline maintenance with different settings. We reviewed the course of biomarker identification, the challenge of overcoming resistance to PARPi and future combinations with targeted therapies, including anti-angiogenic, immune checkpoint inhibitors and DNA damage response inhibitors.
聚（ADP-核糖）聚合酶抑制剂（PARPi）是一类口服抗癌药物，最初作为“合成致死”药物在携带 BRCA1/BRCA2 失活突变的癌症中开发。在高级别浆液性或子宫内膜样卵巢癌（HGOC）中，PARPi 作为复发性 BRCA 突变和非突变肿瘤的维持治疗显示出益处。最近，它们将适应证扩展到一线维持治疗。这篇综述总结了 PARPi 的现状：（i）作为复发疾病的维持或单药治疗，（ii）不同情况下的一线维持治疗。我们回顾了生物标志物鉴定的过程、克服 PARPi 耐药性的挑战以及与靶向治疗（包括抗血管生成、免疫检查点抑制剂和 DNA 损伤反应抑制剂）的未来联合应用。
