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Mechanism to overcome Gleevec resistance demonstrated

PORTLAND, Ore. Amid the glowing results for chronic myelogenous leukemia (CML) patients using Gleevec the past three years, the one reality check has been that a majority of the patients with advanced disease eventually relapse and die of the leukemia.

An article to be published in the Dec. 15 issue of the journal Cancer Research shows that, in the lab, the molecular mutations that produce a resistance to Gleevec can be overcome. Brian Druker, M.D., Howard Hughes Medical Institute Investigator and JELD-WEN Chair of Leukemia Research at the Oregon Health & Science University Cancer Institute, and colleagues report that a compound called PD180970 successfully stopped the activity of several mutations found in patients who developed a resistance to Gleevec.

"The good news is that it appears possible to develop drugs that can overcome the resistance to Gleevec," said Druker. "Although this particular compound is a long way from clinical trials, we've proved a principle and now need to apply it to other compounds that can be developed into effective drugs."

Druker collaborated with pharmaceutical company Novartis to develop Gleevec into a successful treatment for CML. Last year the Food and Drug Administration approved Gleevec in record time for a cancer therapy. Recent studies have shown Gleevec to be up to 10 times more effective than the previous standard treatment for CML, interferon. However, patients whose disease has advanced to the "blast crisis" stage do not fare as well on Gleevec. While 60 percent of advanced CML patients show initial response to the drug, most of those patients relapse after several months.

"Eventually we hope to tailor a treatment to each individual, so if they are prone to a particular molecular mutation, or resistance to Gleevec, we can combine it with a more specific drug that will help overcome that resistance," said Druker.

Gleevec targets the activity of CML cells while leaving normal cells alon
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Contact: Martin Munguia
munguiam@ohsu.edu
503-494-4156
Oregon Health & Science University
15-Dec-2002


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