Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy.Isocitrate dehydrogenases(IDHs)are a class of key proteins in energy me...Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy.Isocitrate dehydrogenases(IDHs)are a class of key proteins in energy metabolism,including IDH1,IDH2,and IDH3,which are involved in the oxidative decarboxylation of isocitrate to yield a-ketoglutarate(a-KG).Mutants of IDH1 or IDH2 can produce D-2-hydroxyglutarate(D-2HG)with a-KG as the substrate,and then mediate the occurrence and development of cancer.At present,no IDH3 mutation has been reported.The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2,implying IDH1 as a promising anti-cancer target.Therefore,in this review,we summarized the regulatory mechanisms of IDH1 on cancer from four aspects:metabolic reprogramming,epigenetics,immune microenvironment,and phenotypic changes,which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies.In addition,we also reviewed available IDH1 inhibitors so far.The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.展开更多
基金supported by National Natural Science Foundation of China(NSFC)(No.81773637,82141216,U1803122)Chunhui Program-Cooperative Research Project of the Ministry of Education+2 种基金Shenyang Young and Middle-aged Innovative Talents Support Program(RC210446,China)Liaoning Province Natural Science Foundation(Nos.2022-MS-241,2020-MZLH-31,China)support from National-Local Joint Engineering Research Center for Molecular Biotechnology of Fujian&Taiwan TCM,Fujian Key Laboratory of Chinese Materia Medica,Fujian University Key Laboratory for Research and Development of TCM Resources,at Fujian University of Traditional Chinese Medicine。
文摘Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy.Isocitrate dehydrogenases(IDHs)are a class of key proteins in energy metabolism,including IDH1,IDH2,and IDH3,which are involved in the oxidative decarboxylation of isocitrate to yield a-ketoglutarate(a-KG).Mutants of IDH1 or IDH2 can produce D-2-hydroxyglutarate(D-2HG)with a-KG as the substrate,and then mediate the occurrence and development of cancer.At present,no IDH3 mutation has been reported.The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2,implying IDH1 as a promising anti-cancer target.Therefore,in this review,we summarized the regulatory mechanisms of IDH1 on cancer from four aspects:metabolic reprogramming,epigenetics,immune microenvironment,and phenotypic changes,which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies.In addition,we also reviewed available IDH1 inhibitors so far.The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.
