Eukaryotic translation initiation factor 4E as a novel therapeutic target in hematological malignancies and beyond

Abstract

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.

Keywords::

• cancer
• eukaryotic translation initiation factor 4E
• M4/M5 acute myeloid leukemia
• metastasis
• mRNA translation
• ribavirin

Notes

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