Mechanisms of resistance to PARP inhibitors - an evolving challenge in oncology

查看全文 作　　者：Angela [1]Mweempwa;Michelle [1]K.Wilson 机构地区：[1]Cancer and Blood,Auckland City Hospital,Auckland 1023,New Zealand 出　　处：《Cancer Drug Resistance》索引2019年第2卷第3期,共10页 摘　　要：Poly-adenosine diphosphate ribose polymerase inhibitors(PARPi)lead to synthetic lethality when used in cancers harbouring a BRCA mutation or homologous recombination deficiency.There are now four PARPi approved by the Food and Drug Administration for therapeutic use is ovarian and breast cancer.In addition to this,there is data supporting its use in pancreatic adenocarcinoma and prostate cancer.However,development of resistance to PARPi limits the duration of response.Key mechanisms found to date include:(1)restoration of homologous recombination;(2)changes in PARP1;(3)suppression of non-homologous end joining;(4)replication fork protection;and(5)drug concentration.Gaining a better understanding of resistance mechanisms may guide combination therapies to overcome the resistance and improve the efficacy of PARPi.The purpose of this review is to describe the resistance mechanisms to PARPi and discuss their early detection. 关 键 词：Poly-adenosine diphosphate ribose polymerase inhibition resistance mechanisms homologous recombination BRCA reversion ovarian cancer