PARP抑制剂联合应用抗肿瘤临床前研究进展
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篇名: PARP抑制剂联合应用抗肿瘤临床前研究进展
TITLE: Progress in preclinical study of combination of PARP inhibitors against tumor
摘要: 多腺苷二磷酸核糖聚合酶(PARP)是一类DNA损伤修复酶。PARP抑制剂包括奥拉帕利(AZD2281)、尼拉帕利(MK-4827)、Rucaparib、Veliparib(ABT-888)、Fluzoparib和Talazoparib(BMN-673)等。本文通过检索相关文献,就PARP抑制剂联合应用抗肿瘤的临床前研究进行综述。通过合成致死模式,PARP抑制剂对具有同源重组修复缺陷的肿瘤细胞具有较强的杀伤作用,但对于DNA损伤修复功能完好的肿瘤细胞,PARP抑制剂往往需要与放疗或其他药物联合发挥作用,联合应用的药物包括抗血管生成药物、热休克蛋白90抑制剂、细胞周期蛋白依赖性激酶12抑制剂、免疫检查点抑制剂、组蛋白脱乙酰酶抑制剂等。PARP抑制剂的联合应用有望增强抗肿瘤药物的疗效,实现增敏增效和逆转耐药的目标,值得进一步开展深入研究并探索新的联合治疗方案。
ABSTRACT: Poly(ADP-ribose)polymerase(PARP)is a kind of DNA damage repair enzyme. PARP inhibitors include Olaparib (AZD2281),Niraparib(MK-4827),Rucaparib,Veliparib(ABT-888),Fluzoparib and Talazoparib (BMN-673),etc. This article reviews the preclinical research on the combined application of PARP inhibitors against tumor by searching the relevant literatures. Through the synthetic lethal mode ,PARP inhibitors have a strong killing effect on tumor cells with homologous recombination repair defects. However ,for tumor cells with intact DNA damage repair function ,PARP inhibitors often need to be combined with radiotherapy or other drugs to play a role. Combined application drugs include antiangiogenic drugs ,heat shock protein 90 inhibitors,cyclin-dependent kinase 12 inhibitors,immune checkpoint inhibitors ,histone deacetylase inhibitors ,etc. The combined application of PARP inhibitors is expected to enhance the efficacy of anti-tumor drugs and achieve the goals of sensitization , synergism and reversal of drug resistance ,which is worthy of further in-depth research and exploration of new combined treatment schemes.
期刊: 2022年第33卷第12期
作者: 张成勇,李玥,杨颖,朱日然
AUTHORS: ZHANG Chengyon g,LI Yue,YANG Ying,ZHU Riran
关键字: 多腺苷二磷酸核糖聚合酶抑制剂;药物联用;抗肿瘤;临床前研究
KEYWORDS: poly(ADP-ribose)polymerase inhibitors ;drug combination ;anti-tumor;preclinical study
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