PARP抑制剂在肿瘤治疗中的研究进展  

Research Progress of PARP Inhibitors in Tumor Therapy

作　　者：沈敏敏[1,2] 徐伟 张博[3] 叶丽冰 林能明 SHEN Minmin;XU Wei;ZHANG Bo;YE Libing;LIN Nengming(Department of Pharmacy,Huzhou Central Hospital,Huzhou 313000,China;College of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China;Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province,Department of Pharmacy,Affiliated Hangzhou First People’s Hospital,Zhejiang University School of Medicine,Hangzhou 310006,China)

机构地区：[1]湖州市中心医院药学部,浙江湖州313000 [2]浙江中医药大学药学院,杭州310053 [3]浙江省临床肿瘤药理与毒理学研究重点实验室,浙江大学医学院附属杭州市第一人民医院药学部,杭州310006

出　　处：《中国现代应用药学》2023年第12期1644-1651,共8页Chinese Journal of Modern Applied Pharmacy

基　　金：浙江省临床肿瘤药理与毒理学研究重点实验室(2020E10021)。

摘　　要：肿瘤是威胁人类生存与健康的重要原因之一。在肿瘤的药物治疗中,化疗是常用手段之一,但由于其特异性低、不良反应大、长期使用易产生耐药性等问题,应用受到较大限制。基于DNA损伤修复机制开发的新型抗肿瘤药物聚腺苷酸二磷酸核糖聚合酶(poly-ADP ribose polymerase,PARP)抑制剂可能是解决这一问题的关键。PARP抑制剂是一类靶向抑制PARP-1蛋白,诱导BRCA基因突变的肿瘤细胞发生“合成致死”现象的新型抗肿瘤药物,已成功应用于卵巢癌、乳腺癌等肿瘤的治疗。近年来PARP抑制剂更是与各类一线化疗药、靶向制剂及免疫检查点抑制剂等进行联合治疗,扩大了临床适用范围。本文将对PARP抑制剂的药理作用与作用机制、在肿瘤治疗中的应用及其耐药机制等研究进展进行总结,以期为PARP抑制剂的临床应用提供合理指导。Tumor is one of the important causes that threaten human survival and health.Chemotherapy is one of the commonly used methods in tumor therapy,but its application is limited by its low specificity,serious adverse drug reaction,and it is also easy to produce drug resistance after long-term use.Novel anti-tumor drug poly-ADP ribose polymerase(PARP)inhibitors based on DNA damage repair mechanisms may be the key to solve this problem.PARP inhibitors are a new class of anti-tumor drugs targeting inhibition of PARP-1 protein and induce“synthetic lethal”phenomenon in tumor cells with BRCA gene mutations.It has been successfully used in the treatment of ovarian cancer,breast cancer and other tumors.In recent years,it has expanded the scope of clinical application through combining with various first-line chemotherapy drugs,targeted drugs and immuno checkpoint inhibitor.In this paper,the pharmacological action and mechanism of PARP inhibitors,the application of PARP inhibitors in tumor therapy and the mechanism of drug resistance of PARP inhibitors will be summarized to provide reasonable guidance for its clinical application.

关 键 词：肿瘤 PARP抑制剂 耐药 DNA损伤修复 

分 类 号：R966[医药卫生—药理学]