Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma

查看全文 作　　者：Danyu [1]Du;Chan [1]Liu;Mengyao [1]Qin;Xiao [1]Zhang;Tao [2]Xi;Shengtao [3]Yuan;Haiping [1,4,5]Hao;Jing [1]Xiong

机构地区：[1]Department of Pharmacology,School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China;[2]Research Center of Biotechnology,School of Life Science and Technology,China Pharmaceutical University,Nanjing 210009,China;[3]Jiangsu Key Laboratory of Drug Screening,China Pharmaceutical University,Nanjing 210009,China;[4]State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009,China;[5]Key Laboratory of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,China

出　　处：《Acta Pharmaceutica Sinica B》索引2022年第12卷第2期,共23页

基　　金：supported by the National Natural Science Foundation of China(No.82070883);Scientific Research Foundation for high-level faculty,China Pharmaceutical University(Nanjing,China)。 摘　　要：Hepatocellular carcinoma(HCC)is an aggressive human cancer with increasing incidence worldwide.Multiple efforts have been made to explore pharmaceutical therapies to treat HCC,such as targeted tyrosine kinase inhibitors,immune based therapies and combination of chemotherapy.However,limitations exist in current strategies including chemoresistance for instance.Tumor initiation and progression is driven by reprogramming of metabolism,in particular during HCC development.Recently,metabolic associated fatty liver disease(MAFLD),a reappraisal of new nomenclature for nonalcoholic fatty liver disease(NAFLD),indicates growing appreciation of metabolism in the pathogenesis of liver disease,including HCC,thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment.In this review,we introduce directions by highlighting the metabolic targets in glucose,fatty acid,amino acid and glutamine metabolism,which are suitable for HCC pharmaceutical intervention.We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment.Furthermore,opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed. 关键词：Metabolic dysregulation Hepatocellular carcinoma GLYCOLYSIS Tricarboxylic acid cycle Pentose phosphate pathway Fatty acidβ-oxidation Glutamine metabolism Cancer therapy

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Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma

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