eIF4E在肿瘤中的生物学功能及靶向治疗的研究现状  

Research Progress of eIF4E's Biological Function in Tumor and Targeted Therapy

作　　者：林帆[1,2] 董良[1,2] 王伟明[2] 黄卫人[2] LIN Fan DONG Liang WANG Weiming HUANG Weiren(Experimental Research Department, Center for Cancer Prevention and Treatment of Sun Yat-sen University, Guangzhou 510060, China Central Laboratory, Shenzhen Second People＇s Hospital, Shenzhen 518039, China)

机构地区：[1]中山大学肿瘤防治中心实验研究部,广州510060 [2]深圳市第二人民医院中心实验室,广东深圳518039

出　　处：《医学综述》2017年第8期1485-1489,1495,共6页Medical Recapitulate

基　　金：中国博士后基金(2015M582463)

摘　　要：真核细胞翻译起始因子4E(eIF4E)在多种肿瘤中上调且活性异常升高,与肿瘤发生、发展及预后密切相关,是靶向治疗研究热点。eIF4E活性主要受磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/AKT/mTOR)及丝裂原活化蛋白激酶/丝裂原活化蛋白激酶作用激酶(MAPK/MNK)通路调控。eIF4E靶向治疗策略主要有:(1)抑制PI3K/AKT/mTOR通路激活;(2)抑制eIF4E表达;(3)抑制eIF4E磷酸化;(4)抑制eIF4F组装;(5)抑制eIF4E-mRNA 5'帽子相互作用;(6)抑制eIF4E依赖的mRNA核质转运。目前,eIF4E靶向药物研究仍处于早期阶段,需深入探索其在不同肿瘤中活化及起始翻译的机制,开发更特异且有效的靶向药物。Eukaryotic translation initiation factor 4E （eIFgE） is frequently up-regulated and aberrantly activated in most tumors. It closely correlates with tumorigenesis and the prognosis of the patient. Therefore, eIF4E has become a promising molecular target for cancer therapy. The activity of elF4E is regulated by hvo major signaling pathways involved in tumorigenesis, including phosphatidy linositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/AKT/ mTOR） and mitogen-activated protein kinase/mitogen-activated protein kinase interacting protein kinases （MAPK/MNK） pathways. At present, there are mainly 6 strategies for targeting eIF4E in cancer therapy, including inhibition of： （1）activation of PI3K/AKT/mTOR pathway; （2） eIF4E expression; （3） eIF4E phosphorylation; （4） eIF4F assembly; （5） eIF4E-mRNA 5＇-cap interaction; （6）eIF4E-dependent mRNA transportation. However, further researches on the regulation mechanism of elF4E activation and translation initiation in different tumors are needed to develop drugs targeting eIF4E with higher specificity and efficacy.

关 键 词：肿瘤 真核细胞翻译起始因子4E 靶向治疗 

分 类 号：R730.2[医药卫生—肿瘤]