PARP抑制剂与免疫检查点抑制剂联合治疗在妇科恶性肿瘤中的应用

PARP Inhibitors Combined with Immune Checkpoint Inhibitors in the Treatment of Gynecological Malignant Tumors

近年来肿瘤靶向和免疫治疗的研究进展迅速,如多腺苷二磷酸核糖聚合酶抑制剂[poly(ADP-ribose)polymerase inhibitor,PARPi]、免疫检查点抑制剂(immune checkpoint inhibitors,ICI)等已改变了妇科肿瘤的传统治疗模式,但部分患者疗效有限或出现耐药。临床前研究发现,PARPi损伤DNA修复过程,可造成肿瘤突变负荷与肿瘤特异性抗原增加,调节肿瘤微环境,刺激肿瘤浸润淋巴细胞(tumor infiltrating lymphocytes,TIL)产生并促进抗肿瘤免疫反应,为PARPi与ICI联合治疗提供了理论基础。近年多项临床研究发现PARPi与ICI联合使用可显著改善妇科恶性肿瘤患者的预后。

In recent years the progress of targeted therapy and immunotherapy has developed rapidly,such as poly(ADP-ribose)polymerase inhibitor(PARPi)and immune checkpoint inhibitors(ICI)have changed the traditional treatment pattern of gynecologic tumors,but some patients have limited efficacy or develop drug resistance.Preclinical studies have found that PARPi damages DNA repair process,results in increasing tumor mutation burden and tumor-specific antigen neoantigens,modulates the tumor microenvironment,and stimulates the production of tumor infiltrating lymphocytes(TIL)and promotes anti-tumor immune response,which providing a theoretical basis for the combination treatment of PARPi and ICI.Recently,many clinical studies have found that the combination of PARPi and ICI can significantly improve the prognosis of patients with gynecological malignant tumors.