PARP抑制剂耐药机理的研究进展  

Advances in the mechanisms of PARP inhibitor resistance

作　　者：杨馥珺 冯笑山[1] YANG Fujun;FENG Xiaoshan(The First Affiliated Hospital,College of Clinical Medicine of Henan University of Science and Technology,Henan Luoyang 471003,China)

机构地区：[1]河南科技大学临床医学院,河南科技大学第一附属医院,河南洛阳471003

出　　处：《现代肿瘤医学》2022年第10期1894-1897,共4页Journal of Modern Oncology

摘　　要：聚ADP-核糖聚合酶(Poly ADP-ribose polymerase,PARP)抑制剂(PARPi)是一组靶向携带BRCA1/2或其他同源重组因子有害突变的乳腺癌与卵巢癌的新型抗癌药物。PARPi的临床应用已取得显著成果,是近年来临床肿瘤学的重大突破之一。然而,PARPi耐药正在成为一个严重的临床问题。研究和了解PARPi耐药机理对克服肿瘤耐药和提高疗效具有重要意义。最近的研究进展已经揭示了一些诱发PARPi耐药的机制,包括上调多药耐药基因,改变PARylation酶,重建同源重组修复和恢复复制叉稳定性。本文将综述这些变化如何导致癌细胞对PARPi产生耐药并讨论克服PARPi耐药的可能策略。Poly ADP-ribose polymerase(PARP)inhibitors(PARPi)is a group of novel anticancer agents targeting breast and ovarian cancers with disruptive mutations in BRCA1/2 or other homologue recombination(HR)factors.Clinical application of PARPi has achieved significant outcomes,which is one of the major breakthroughs in clinical oncology in recent years.However,PARPi resistance is emerging as a major clinical problem.Investigation and understanding the mechanisms of PARPi resistance is of pivotal significance for overcoming the potential resistance and improving the therapeutic efficacy.Recent advances have identified a few mechanisms that contribute to PARPi resistance,including upregulation of multidrug resistant genes,modification of PARylation enzymes,restoration of homologous recombination repair and/or stabilization of the replication forks.This review will discuss how these changes render the cancer cells resistant to PARPi and the potential strategies that may be used to overcome the resistance.

关 键 词：PARP抑制剂 耐药 乳腺癌 卵巢癌 BRCA DNA损伤修复 

分 类 号：R730.5[医药卫生—肿瘤]