Targeting histone deacetylases for cancer therapy: Trends and challenges  

作　　者：Tao Liang Fengli Wang Reham M.Elhassan Yongmei Cheng Xiaolei Tang Wengang Chen Hao Fang Xuben Hou 

机构地区：[1]Department of Pharmacy,the Second Hospital Affiliated Wannan Medical College,Wuhu 241000,China [2]Department of Science and Education,Translational Medicine Center&Vascular Disease Research Center,the Second Hospital Affiliated Wannan Medical College,Wuhu 241000,China [3]Clinical Pathogens Detection Engineering Center of Wuhu,Wuhu 241000,China [4]Department of Medicinal Chemistry and Key Laboratory of Chemical Biology(Ministry of Education),School of Pharmaceutical Sciences,Cheeloo College of Medicine,Shandong University,Jinan 250012,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第6期2425-2463,共39页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China (81874288, 82003590 and 92053105);the Natural Science Foundation of Shandong Province (ZR2020QH342, China);the Key Project of Natural Science Foundation of Anhui Province for College Scholar (2022AH051216, China);Scientific Research Project of Anhui Provincial Health Commission (AHWJ2022b005, China)。

摘　　要：Dysregulation of histone deacetylases(HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors(HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.

关 键 词：HDACS ONCOGENESIS Selective inhibitor Combination therapy Multitarget agent PROTAC 

分 类 号：R730.5[医药卫生—肿瘤]