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It's a knock out: eIF4E-specific anti-sense oligonucleotides knock down cancer

A new study by Jeremy Graff and colleagues from Eli Lilly and Company has demonstrated the anti-cancer effect of a new therapeutic in a mouse model of human tumors and has spawned clinical trials to test the ability of this therapeutic to treat human cancers. As highlighted in the accompanying commentary by Celeste Simon and colleagues from the University of Pennsylvania, Philadelphia, if the therapeutic is as effective in clinical trials as it was in mice it will be useful for the treatment of a broad range of cancers.

The growth of many tumors is promoted by increased expression of the protein eIF4E, but no eIF4E-specific therapy has yet been developed. In this study, the intravenous administration of eIF4E-specific antisense oligonucleotides (ASOs) to mice bearing human tumors substantially inhibited tumor growth. Importantly, although these ASOs also decreased eIF4E expression in normal tissues, the function of the normal tissues analyzed was not compromised. The authors therefore suggest that tumor cells are more susceptible to decreased expression of eIF4E than normal cells, meaning that eIF4E-specific ASOs should not cause damage to normal tissues.

TITLE: Therapeutic suppression of translation initiation factor eIF4E expression reduces tumor growth without toxicity


Jeremy R. Graff
Eli Lilly and Company, Indianapolis, Indiana, USA.
Phone: (317) 277-0220; Fax: (317) 277-3652; E-mail:

View the PDF of this article at:


TITLE: Taking aim at translation for tumor therapy


M. Celeste Simon
Abramson Family Cancer Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Phone: (215) 746-5532; Fax: (215) 746-5511; E-mail:

View the PDF of this article at:

Contact: Karen Honey
Journal of Clinical Investigation

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