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首页> 外文期刊>Expert opinion on therapeutic targets >Eukaryotic translation initiation factor 4E as a novel therapeutic target in hematological malignancies and beyond
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Eukaryotic translation initiation factor 4E as a novel therapeutic target in hematological malignancies and beyond

机译：真核翻译起始因子4E作为血液系统恶性肿瘤及其他恶性肿瘤的新型治疗靶标

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Introduction: The eukaryotic translation initiation factor 4E (eIF4E) is a key regulator of protein synthesis, and an oncogene. Its expression and activity are frequently elevated in cancer, and have been shown to correlate with poor prognosis. Efforts to target eIF4E have thus yielded much interest, with some clinical success. Areas covered: We provide an overview of eIF4E function and regulation, and its role in hematological malignancies and solid tumors. Activation of eIF4E via upstream signaling pathways that are frequently deregulated in cancer and the role of eIF4E phosphorylation are discussed. We present an updated review of different approaches to target eIF4E function in the lab and in the clinic. Expert opinion: The prospect of effectively targeting eIF4E in cancer is very attractive, because eIF4E is a common downstream node on which multiple oncogenic signaling pathways converge. However, efforts to do so have yielded limited clinical success so far. While active-site inhibitors of mammalian target of rapamycin show some promise, and inhibitors of eIF4E phosphorylation may emerge as clinical candidates, the only drug to date that has demonstrated antitumor activity associated with eIF4E inhibition in patients is ribavirin. Further studies will certainly aid the design of better compounds and rational combination therapies.
机译：简介：真核翻译起始因子4E（eIF4E）是蛋白质合成的关键调节剂，也是一种癌基因。它的表达和活性在癌症中经常升高，并已表明与不良预后相关。因此，靶向eIF4E的努力引起了人们的极大兴趣，并取得了一些临床成功。涵盖的领域：我们概述了eIF4E的功能和调控，及其在血液系统恶性肿瘤和实体瘤中的作用。讨论了通过在癌症中经常失活的上游信号通路激活eIF4E以及eIF4E磷酸化的作用。我们提供了在实验室和临床中针对eIF4E功能的不同方法的最新综述。专家意见：在癌症中有效靶向eIF4E的前景非常诱人，因为eIF4E是常见的下游节点，多个致癌信号通路在其上汇合。但是，到目前为止，这样做的努力在临床上取得的成功有限。尽管哺乳动物雷帕霉素靶标的活性部位抑制剂显示出一定的前景，并且eIF4E磷酸化抑制剂可能会作为临床候选药物出现，但迄今为止，唯一已证明与患者抑制eIF4E有关的抗肿瘤活性的药物是利巴韦林。进一步的研究无疑将有助于设计更好的化合物和合理的联合疗法。

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