聚腺苷二磷酸核糖聚合酶抑制剂耐药性研究进展-药学进展.pdf

PROGRESS IN PHARMACEUTICAL SCIENCES 2016,40 2 :122-128 122 ( ) ·前沿与进展· A D VA N C E S I N P H A R M A C E U T I C A L S C I E N C E S 聚腺苷二磷酸核糖聚合酶抑制剂耐药性研究进展 焦贺，陈雨，谢周令，李志裕* ( 中国药科大学药学院，江苏 南京 210009) [ 摘要 ] 聚腺苷二磷酸核糖聚合酶（PARP）抑制剂可选择性杀死同源重组功能缺陷的肿瘤细胞，而对正常细胞的危害较小，这是“合成致死” 理论应用于临床的典型范例。尽管 PARP 抑制剂作为一种新型靶向药物，极具应用潜力，但其临床应用也面临诸多问题，其中耐药性的产 生被认为是限制 PARP 抑制剂临床应用的重要原因之一。简介 PARP-1 的功能及 PARP-1 抑制剂研究进展，着重综述 PARP-1 抑制剂耐药 的临床表现、可能的发生机制及逆转策略，为 PARP-1 抑制剂的临床合理应用提供参考。 [ 关键词 ] 聚腺苷二磷酸核糖聚合酶；PARP-1 抑制剂；耐药机制； 耐药逆转 [ 中图分类号 ] R979.1; R969.3 [ 文献标志码 ] A [ 文章编号 ] 1001-5094（2016）02-0122-07 Progress in the Study of Resistance to Poly(ADP-ribose)polymerase Inhibitors , , , JIAO He CHEN Yu XIE Zhouling LI Zhiyu (School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China) [Abstract] Poly (ADP-ribose) polymerase (PARP) inhibitors can selectively kill cancer cells with functional homologous recombination deficiency and have minimal toxicity to normal cells. They are typical exemplifications to clinically treat cancers by “synthetic lethality” theory. Although PARP inhibitors, as a novel type of targeted drugs, have great potential for application, they still face many challenges that restrict their clinical applications including especially the emergence of resistance. The function of PARP-1 and the development of PARP-1 inhibitors were introduced. The clinical resistance to PARP-1 inhibitors as well as the potential mechanisms and reversal strategies for the resistance were highlighted so as to provide references for the clinical rational use of PARP-1 inhibitors. [Key word