Kim Yevgeniy, Kim Aleksei, Sharip Ainur, Sharip Aigul, Jiang Juhong, Yang Qing, Xie Yingqiu
Department of Biology, Nazarbayev University, School of Science and Technology, Astana, 010000, Republic of Kazakhstan.
Department of Pathology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Int J Biol Sci. 2017 Feb 17;13(2):198-208. doi: 10.7150/ijbs.17240. eCollection 2017.
One of the DNA repair machineries is activated by Poly (ADP-ribose) Polymerase (PARP) enzyme. Particularly, this enzyme is involved in repair of damages to single-strand DNA, thus decreasing the chances of generating double-strand breaks in the genome. Therefore, the concept to block PARP enzymes by PARP inhibitor (PARPi) was appreciated in cancer treatment. PARPi has been designed and tested for many years and became a potential supplement for the conventional chemotherapy. However, increasing evidence indicates the appearance of the resistance to this treatment. Specifically, cancer cells may acquire new mutations or events that overcome the positive effect of these drugs. This paper describes several molecular mechanisms of PARPi resistance which were reported most recently, and summarizes some strategies to reverse this type of drug resistance.
其中一种DNA修复机制由聚（ADP-核糖）聚合酶（PARP）激活。特别地，这种酶参与单链DNA损伤的修复，从而降低基因组中产生双链断裂的几率。因此，通过PARP抑制剂（PARPi）阻断PARP酶的概念在癌症治疗中受到重视。PARPi已经设计和测试多年，并成为传统化疗的一种潜在补充。然而，越来越多的证据表明出现了对这种治疗的耐药性。具体而言，癌细胞可能获得新的突变或事件，从而克服这些药物的积极作用。本文描述了最近报道的PARPi耐药的几种分子机制，并总结了一些逆转这种耐药性的策略。
