title: Eukaryotic translation initiation factor 4E as a novel therapeutic target in hematological malignancies and beyond.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: McGill University, Lady Davis Institute for Medical Research, Jewish General Hospital, Segal Cancer Centre , Montreal, Quebec H3T 1E2 , Canada +1 514 340 8222, Ext. 4365 ; +1 514 340 8717 ; wmiller@ldi.jgh.mcgill.ca.
authors.forename: Filippa
authors.initials: F
authors.lastname: Pettersson
authors.forename: Sonia V
authors.initials: SV
authors.lastname: Del Rincon
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Miller
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015195:Drug Design; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011379:Prognosis; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D039561:Eukaryotic Initiation Factor-4E
keywords: M4/M5 acute myeloid leukemia; cancer; eukaryotic translation initiation factor 4E; mRNA translation; metastasis; ribavirin