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New leukemia drug shows promise in overriding all Gleevec resistance

(PHILADELPHIA) Temple University researchers have developed a new drug that could potentially treat all forms of Gleevec-resistant chronic myelogenous leukemia (CML). Their work is published in this week's early edition of Proceedings of the National Academy of Sciences.

According to lead researcher, Prem Reddy, Ph.D., professor of biochemistry and Director of the Fels Institute for Cancer Research at Temple University School of Medicine, most patients with advanced CML, a rare but deadly form of cancer, typically develop resistance to Gleevec, the most successful treatment for CML to date, within a few years of starting the therapy.

CML is caused by the Philadelphia chromosome, an abnormality that produces a cancer protein called BCR-ABL. Gleevec works by binding to BCR-ABL and completely blocking its activity, thereby stopping cancer growth. When Gleevec came to market about four years ago, it was widely hailed as a miracle drug. For the first time, there was hope for this group of patients.

"Gleevec has been a remarkable success for the treatment of CML. However, a significant number of patients eventually develop resistance to it because their cancer cells are able to mutate and adapt," said Reddy.

Since discovering this phenomenon, scientists have sought new ways to prevent or overcome this resistance. Recently, two experimental drugs were found to be effective in circumventing some but not all forms of Gleevec resistance. Both, for instance, failed to block the activity of a mutant BCR-ABL, called T315I, which is one of the more predominant mutations seen in Gleevec-resistant patients.

Reddy and his research team sought instead to develop a drug that would circumvent all of the mutations and therefore all forms of resistance. They focused on other possible avenues to inhibit the actions of BCR-ABL. To do so, they targeted parts of the BCR-ABL protein that didn't appear to be mutating and adapting to Gleevec.
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Contact: Eryn Jelesiewicz
dobeck@temple.edu
215-707-0730
Temple University
24-Jan-2005


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