PARP抑制剂与PD-1/PD-L1抑制剂在卵巢癌治疗中的联合应用

doi:10.12280/gjfckx.20230289

摘要/Abstract

摘要：

卵巢癌是妇科三大恶性肿瘤之一，也是致死率最高的女性生殖系统恶性肿瘤。目前卵巢癌的治疗方式主要为卵巢癌细胞减灭术+铂类与紫杉醇联合化疗，但其复发率和耐药率较高。近年来肿瘤免疫治疗的研究进展迅速，尤其是对程序性死亡受体1（programmed death-1，PD-1）及其配体（programmed death-ligand 1，PD-L1）的研究已在多种肿瘤中取得了成效。但是，许多临床试验发现PD-1/PD-L1抑制剂单药用于卵巢癌治疗效果并不理想。多腺苷二磷酸核糖聚合酶抑制剂[poly (ADP-ribose) polymerase inhibitor，PARPi]是一种癌症靶向治疗药物，通过合成致死作用杀伤肿瘤细胞。近期研究表明，PARPi除了其本身的细胞毒性作用之外，还具有免疫调节作用，能与PD-1/PD-L1抑制剂产生协同效应，二者联合使用可显著改善患者预后。综述PD-1/PD-L1抑制剂与PARPi在卵巢癌治疗中联合使用的作用机制和临床应用的研究进展。

关键词: 卵巢肿瘤, 免疫疗法, 分子靶向治疗, 多(ADP核糖)聚合酶抑制剂, 免疫检查点抑制剂, PD-1/PD-L1抑制剂

Abstract:

Ovarian cancer is one of the three major gynecological malignancies and the most lethal malignancy of female reproductive system. At present, the main treatment methods for ovarian cancer are primary debulking surgery and platinum-based chemotherapy, but the recurrence rate and drug resistance rate remain high. In recent years, the development of tumor immunotherapy has progressed rapidly, especially the research on programmed death-1(PD-1) and programmed death-ligand 1 (PD-L1), which has been achieved on a variety of tumors. However, many clinical trials have found that PD-1/PD-L1 inhibitors alone are not effective in treating ovarian cancer. The poly (ADP-ribose) polymerase inhibitor (PARPi) is a type of targeted medicine that kills tumor cells through synthetic lethal effect. Recent studies have shown that PARPi has immunomodulatory effects in addition to its own cytotoxic effects, and can have a synergistic effect with PD-1/PD-L1 inhibitors, and the combination of the two can significantly improve patient prognosis. Therefore, this article reviews the research progress on the mechanism of action and clinical application of PD-1/PD-L1 inhibitor combined with PARPi in the treatment of ovarian cancer.

Key words: Ovarian neoplasms, Immunotherapy, Molecular targeted therapy, Poly(ADP-ribose) polymerase inhibitors, Immune checkpoint inhibitors, PD-1/PD-L1 inhibitor

郭京京, 张云凤, 王悦. PARP抑制剂与PD-1/PD-L1抑制剂在卵巢癌治疗中的联合应用[J]. 国际妇产科学杂志, 2023, 50(5): 568-572.

GUO Jing-jing, ZHANG Yun-feng, WANG Yue. The Combined Application of PARP Inhibitor and PD-1/PD-L1 Inhibitor in the Treatment of Ovarian Cancer[J]. Journal of International Obstetrics and Gynecology, 2023, 50(5): 568-572.

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