卵巢癌对聚腺苷二磷酸核糖聚合酶抑制剂耐药机制的研究进展

Research progress on the mechanism of ovarian cancer resistance to poly (ADP-ribose) polymerase inhibitors

聚腺苷二磷酸核糖聚合酶(PARP)抑制剂类药物的问世是近年来肿瘤靶向治疗领域中的重要突破之一,其对于卵巢癌的治疗效果颇为显著。然而,一部分患者对于PARP抑制剂的治疗并不敏感,这种耐药现象限制了其在卵巢癌中的应用。探讨PARP抑制剂耐药机制、寻找克服耐药策略成为进一步扩大PARP抑制剂获益人群的迫切需求。现有研究表明,卵巢癌对PARP抑制剂耐药的主要机制有同源重组修复活性恢复、相关信号通路因子表达异常、药物外排作用和复制叉稳定性改变等。本文将就卵巢癌对PARP抑制剂耐药机制的研究进展作一综述,旨在为PARP抑制剂在临床中的合理应用提供理论依据,并对克服耐药策略的探索提供参考思路。

In recent years,the advent of poly(ADP-ribose)polymerase(PARP)inhibitors is one of the important breakthroughs in the field of tumor-targeted therapy,and its therapeutic effect on ovarian cancer is quite significant.However,some patients are not sensitive to PARP inhibitors,and this phenomenon limits the application of PARP inhibitors in ovarian cancer.Exploring the mechanism of PARP inhibitor resistance and finding strategies to overcome resistance have become an urgent need to expand the benefit population of PARP inhibitors.It is shown that the main mechanisms of ovarian cancer resistance to PARP inhibitors include recovery of homologous recombination repair,abnormal expression of related signaling pathway factors,drug efflux,and changes in the stability of replication forks.This review will summarize the research progress on the mechanism of ovarian cancer resistance to PARP inhibitors,which aims to provide a theoretical basis for the rational application of PARP inhibitors in clinical practice,and provide reference ideas for the exploration of strategies to overcome drug resistance.