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中华临床医师杂志(电子版) ›› 2024, Vol. 18 ›› Issue (06) : 584 -588. doi: 10.3877/cma.j.issn.1674-0785.2024.06.010

综述

PARP抑制剂治疗卵巢癌的耐药机制及应对策略
徐靖亭1, 孔璐1,()   
  1. 1. 100069 北京,首都医科大学生物化学与分子生物学教研室
  • 收稿日期:2024-04-30 出版日期:2024-06-15
  • 通信作者: 孔璐
  • 基金资助:
    首都医科大学长学制导师科研训练项目(CXZDS2022038)

Mechanisms of resistance to PARP inhibitors in ovarian cancer and strategies to overcome such resistance

Jingting Xu1, Lu Kong1,()   

  1. 1. Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
  • Received:2024-04-30 Published:2024-06-15
  • Corresponding author: Lu Kong
引用本文:

徐靖亭, 孔璐. PARP抑制剂治疗卵巢癌的耐药机制及应对策略[J]. 中华临床医师杂志(电子版), 2024, 18(06): 584-588.

Jingting Xu, Lu Kong. Mechanisms of resistance to PARP inhibitors in ovarian cancer and strategies to overcome such resistance[J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(06): 584-588.

卵巢癌致死率居妇科肿瘤之首,DNA损伤修复缺陷是卵巢癌发生的重要原因之一。乳腺癌易感基因(BRCA)1和2缺失突变的频发,导致卵巢癌中同源重组修复(HRR)机制障碍。近年研究指出,作为DNA损伤修复的关键酶,多聚ADP-核糖聚合酶1(PARP1)的基因与BRCA1/2双突变具有合成致死效应,因此PARP抑制剂(PARPi),如奥拉帕尼、尼拉帕尼和氟唑帕尼等获批作为新一代卵巢癌的靶向药物。然而,长期使用PARPi的患者大多出现了不同程度的耐药性,甚至出现与顺铂等抗肿瘤药物的交叉耐药。现将可能的耐药机制和应对策略进行综述。

The mortality of ovarian cancer ranks first among gynecological tumors, and defective DNA damage repair is one of the important causes of ovarian cancer. Frequent deletion mutations in breast cancer susceptibility genes (BRCA) 1 and 2 contribute to the impairment of homologous recombination repair (HRR) in ovarian cancer. Researchers have recently shown that the gene encoding poly(ADP-ribose) polymerase 1 (PARP1), a key enzyme for DNA repair, is synthetically lethal with BRCA1/2 double mutations. Therefore, PARP inhibitors (PARPi), such as olaparib, niraparib, and fluzoparib, have been approved as a new generation of targeted agents for ovarian cancer therapy. However, most patients with long-term PARPi therapy have varying degrees of drug resistance and even cross-resistance with cisplatin and other antitumor drugs. This article reviews the possible mechanisms of resistance to PARP inhibitors in ovarian cancer and corresponding coping strategies.

图1 卵巢癌PARPi耐药机制总结 注:SSBR为DNA单链损伤修复
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