卵巢癌中PARP抑制剂耐药机制及耐药后再次使用PARP抑制剂的研究进展

Research Progress on Mechanisms of Resistance to PARP Inhibitors in Ovarian Cancer and Its Re-Administration in Resistant Patients

在妇科肿瘤中,卵巢癌具有复发率高、病死率高、预后差的特点,是危害女性生命健康的恶性肿瘤之一。近年来,聚二磷酸腺苷核糖聚合酶抑制剂(poly ADP ribose polymerase inhibitor,PARPi)作为一组新型的小分子靶向药物在卵巢癌临床治疗应用中取得了一定成效,然而耐药反应成为了PARPi在临床实践中的巨大挑战。随着PARPi在临床上应用的增多,克服耐药的问题逐渐成为人们关注的重点。已有临床试验证实耐药后再次使用PARPi的可行性,同时PARPi与抗血管生成药物、免疫检查点阻滞剂等联合应用方案,在PARPi耐药后重新恢复PARPi敏感性的探索也在不断进行中。全文主要就PARPi耐药机制及PARPi耐药后再次使用PARPi的新策略进行综述,为临床工作提供参考。

Ovarian cancer is a common gynecological malignant tumor with high recurrence rate and poor prognosis.Poly ADP ribose polymerase inhibitors(PARPi)as a novel type of small molecule targeted drugs have achieved good effect in the treatment of ovarian cancer,however,resistance to PARPi has become a great challenge clinically.With the increasing application of PARPi,overcoming drug resistance has become the focus of clinical studies.Clinical trials have confirmed the feasibility of re-treatment with PARPi in ovarian cancer patients after drug resistance.The combined application of PARPi with anti-angiogenic agents,immune checkpoint inhibitors and other drugs has been explored to restore PARPi sensitivity after resistance.In this paper,we review the mechanisms of PARPi resistance and new strategies of re-treatment with PARPi in ovarian cancer patients after resistance occurred.