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Cancer Research 68, 631, February 1, 2008. doi: 10.1158/0008-5472.CAN-07-5635
© 2008 American Association for Cancer Research

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Targeting the Eukaryotic Translation Initiation Factor 4E for Cancer Therapy

Jeremy R. Graff1, Bruce W. Konicek1, Julia H. Carter2 and Eric G. Marcusson3

1 Cancer Growth and Translational Genetics, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana; 2 Wood Hudson Cancer Research Laboratory, Newport, Kentucky; and 3 Isis Pharmaceuticals, Carlsbad, California

Requests for reprints: Jeremy R. Graff, Cancer Growth and Translational Genetics, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, DC 0546, Indianapolis, IN 46285. Phone: 317-277-0220; Fax: 317-277-3652; E-mail: Graff_jeremy{at}lilly.com.

Key Words: antisense oligonucleotide • eIF4E • translational control

The eukaryotic translation initiation factor 4E (eIF4E) is frequently overexpressed in human cancers in relation to disease progression and drives cellular transformation, tumorigenesis, and metastatic progression in experimental models. Enhanced eIF4E function results from eIF4E overexpression and/or activation of the ras and phosphatidylinositol 3-kinase/AKT pathways and selectively increases the translation of key mRNAs involved in tumor growth, angiogenesis, and cell survival. Consequently, by simultaneously and selectively reducing the expression of numerous potent growth and survival factors critical for malignancy, targeting eIF4E for inhibition may provide an attractive therapy for many different tumor types. Recent work has now shown the plausibility of therapeutically targeting eIF4E and has resulted in the advance of the first eIF4E-specific therapy to clinical trials. These studies illustrate the increased susceptibility of tumor tissues to eIF4E inhibition and support the notion that the enhanced eIF4E function common to many tumor types may represent an Achilles' heel for cancer. [Cancer Res 2008;68(3):631–4]




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Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2008 by the American Association for Cancer Research.