基于合成致死的抗肿瘤药物研发进展  

Research progress for the development of anti-tumor drugs based on synthetic lethality

作　　者：陈培 母波 宾华超 杨胜勇[2] Chen Pei;Mu Bo;Bin Huachao;Yang Shengyong(Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education,West China School of Pharmacy,Sichuan University,Chengdu 610041,Sichuan,China;State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,Sichuan University,Chengdu 610041,Sichuan,China)

机构地区：[1]四川大学华西药学院靶向药物及释药系统教育部重点实验室,四川成都610041 [2]四川大学华西医院生物治疗国家重点实验室,四川成都610041

出　　处：《生物医学转化》2022年第1期1-12,共12页Biomedical transformation

摘　　要：合成致死是指在两个非致死基因中任何一个基因发生突变均不影响细胞存活,但当两个基因同时发生突变时,能够特异性导致细胞死亡。恶性肿瘤由于DNA复制和修复的错误积累了大量的基因突变,因此可抑制与这些基因具有合成致死关系的另一个基因,从而选择性地杀死肿瘤细胞,而不影响正常细胞。近年来,合成致死原理已经成功应用于肿瘤的靶向治疗。本文综述了合成致死的基本原理、合成致死相互作用的筛选方法、合成致死在DNA损伤修复领域的研究现状、合成致死在抗肿瘤药物研发中的挑战及展望。Synthetic lethality describes a phenomenon where mutation of any one of two non-lethal genes does not affect cell survival,whereas mutation of both genes significantly compromise cell viability.Malignant tumors accumulate a large number of genetic mutations due to errors in DNA replication and repair.Inhibiting another gene that has a synthetic lethal relationship with one of these genes may selectively kill tumor cells without affecting normal cells.In recent years,the principle of synthetic lethality has been successfully applied to the targeted therapy of tumors.This article reviews the basic principles of synthetic lethality,the screening methods for synthetic lethal interactions,the research status of synthetic lethality in the field of DNA damage repair,and the challenges and prospects of synthetic lethality in the development of antitumor drugs.

关 键 词：合成致死 DNA损伤修复 PARP抑制剂 抗肿瘤药物 

分 类 号：R979.1[医药卫生—药品]