Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy  

作　　者：Zhi-Qiang Wang Zhao-Cong Zhang Yu-Yang Wu Ya-Nan Pi Sheng-Han Lou Tian-Bo Liu Ge Lou Chang Yang 

机构地区：[1]Department of Gynecology Oncology,Harbin Medical University Cancer Hospital,Harbin 150086,China [2]School of Optometry and Ophthalmology and Eye Hospital,Wenzhou Medical University,Wenzhou,China [3]Department of Colorectal Surgery,Harbin Medical University Cancer Hospital,Harbin,China

出　　处：《Signal Transduction and Targeted Therapy》2023年第12期5631-5656,共26页信号转导与靶向治疗（英文）

基　　金：supported by the National Natural Science Foundation of China(nos.81872507 and 82173238);the Heilongjiang Provincial Natural Science Foundation Key Projects(ZD2020H007);the Harbin Medical University Cancer Hospital(CN)Nn10 Project(Nn10py2017-01);the China Postdoctoral Science Foundation(296266);the Heilongjiang Province Doctoral Post-doctoral Fund(LBH-Z21177);the Fundamental Research Funds for the Provincial Universities(2022-KYYWF-0291);the Harbin Medical University Haiyan Youth Fund(JJQN2022-3).

摘　　要：BET proteins,which influence gene expression and contribute to the development of cancer,are epigenetic interpreters.Thus,BET inhibitors represent a novel form of epigenetic anticancer treatment.Although preliminary clinical trials have shown the anticancer potential of BET inhibitors,it appears that these drugs have limited effectiveness when used alone.Therefore,given the limited monotherapeutic activity of BET inhibitors,their use in combination with other drugs warrants attention,including the meaningful variations in pharmacodynamic activity among chosen drug combinations.In this paper,we review the function of BET proteins,the preclinical justification for BET protein targeting in cancer,recent advances in small-molecule BET inhibitors,and preliminary clinical trial findings.We elucidate BET inhibitor resistance mechanisms,shed light on the associated adverse events,investigate the potential of combining these inhibitors with diverse therapeutic agents,present a comprehensive compilation of synergistic treatments involving BET inhibitors,and provide an outlook on their future prospects as potent antitumor agents.We conclude by suggesting that combining BET inhibitors with other anticancer drugs and innovative next-generation agents holds great potential for advancing the effective targeting of BET proteins as a promising anticancer strategy.

关 键 词：DRUGS holds meaningful 

分 类 号：R730.5[医药卫生—肿瘤]