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聚腺苷二磷酸核糖聚合酶(PARP)与程序性死亡受体 1/配体 1(PD-1/PD-L1)检查点抑制剂在复发性或转移性子宫内膜癌中的应用。

PARP and PD-1/PD-L1 checkpoint inhibition in recurrent or metastatic endometrial cancer.

机构信息

Departments of Medical Oncology, Leiden, the Netherlands; Departments of Radiation Oncology Leiden, the Netherlands.

Departments of Medical Oncology, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands.

出版信息

Crit Rev Oncol Hematol. 2020 Aug;152:102973. doi: 10.1016/j.critrevonc.2020.102973. Epub 2020 May 18.

Abstract

The prognosis of recurrent or metastatic endometrial cancer is poor, with five-year survival of only 10-20 %. First-line therapy consists of either platinum-based chemotherapy or hormonal therapy. No standard subsequent-line therapy has been identified. In recent years, significant progress has been made in the knowledge on underlying molecular biology of endometrial cancer and potential targets for therapy have been identified. Targeted therapies as poly (ADP-ribose) polymerase (PARP) inhibitors and immunotherapy as PD-1/PD-L1 checkpoint inhibitors have the potential to be effective against specific subtypes of endometrial cancer. Preclinical studies have shown that combining these agents may result in a synergistic effect. In this review, we focus on the molecular basis of checkpoint inhibition and targeted therapy as PARP inhibition in endometrial cancer and summarize available clinical data, and ongoing and planned clinical trials that investigate these agents as mono- or combination therapies in endometrial cancer and where relevant, other gynecological cancers.

摘要

复发性或转移性子宫内膜癌的预后较差,五年生存率仅为 10-20%。一线治疗包括铂类化疗或激素治疗。目前尚未确定标准的二线治疗方法。近年来,人们对子宫内膜癌基础分子生物学的认识取得了重大进展,已经确定了潜在的治疗靶点。针对这些靶点的治疗方法包括聚(ADP-核糖)聚合酶(PARP)抑制剂和免疫疗法,如 PD-1/PD-L1 检查点抑制剂,有可能对特定类型的子宫内膜癌有效。临床前研究表明,联合使用这些药物可能会产生协同作用。在这篇综述中,我们重点介绍了子宫内膜癌中检查点抑制和靶向治疗(如 PARP 抑制)的分子基础,并总结了这些药物作为单一或联合治疗在子宫内膜癌以及相关的其他妇科癌症中的现有临床数据、正在进行和计划进行的临床试验。

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