Ribavirin Shows Promise in Leukemia Clinical Trial

The carcinogenic effect of eIF4E is linked to its ability to bind the 7-methyl guanosine (m7G) cap on mRNAs, thereby selectively enhancing eIF4E dependent nuclear mRNA export and translation.

To inhibit the activity of eIF4E in a group of AML patients, investigators at the University of Montreal (Canada) treated them with the antiviral drug ribavirin, which physically mimics the m7G RNA cap. Results published in the May 11, 2009, online edition of the journal Blood revealed that among the group of 11 patients there were: one complete remission, two partial remissions, two blast responses, four patients with stable disease, and two with progressive disease.

Ribavirin induced nuclear eIF4E to relocalize to the cytoplasm, and the reduction in levels of nuclear eIF4E was associated with positive clinical response. Lack of response or relapse coincided with continued or renewed nuclear localization of eIF4E.

"Our results are the first to show that targeting eIF4E in humans is clinically beneficial," said senior author Dr. Katherine Borden, professor of pathology and cell biology at the University of Montreal. "We also found that ribavirin not only blocks eIF4E, it has no side effect on patients. Combination therapy with chemotherapeutic agents may enhance the efficacy of this treatment. Trials in the near future are planned to overcome resistance to ribavirin, and we are looking forward to more complete remissions. We also hope to test whether ribavirin is as effective in the treatment of other cancers with dysregulated eIF4E. Our laboratory studies suggest this is likely."

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