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Small molecule may disarm enemy of cancer-fighting p53
Date:12/7/2010

ORLANDO A pioneering clinical trial is testing the effectiveness in leukemia of a small molecule that shuts down MDM2, a protein that can disable the well-known tumor suppressor p53.

Michael Andreeff, M.D., Ph.D., professor of Medicine and chief of Molecular Hematology and Therapy in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, presented preliminary results of this ongoing Phase I study at the 52nd Annual Meeting of the American Society of Hematology. The clinical trial is under way at MD Anderson and five other sites in the United States and United Kingdom.

The first-in-class drug has shown clinical activity in some patients and been well-tolerated, Andreeff said.

Andreeff has been researching the interaction between MDM2 and p53 for five years. He says he believes this study may lead to an effective new way to fight some types of cancer with fewer side effects.

"P53 can be activated by chemotherapy or radiation, but both of these therapies carry risks of causing secondary tumors," he said. "If we can activate this tumor-suppressor with a method that is non-genotoxic and does not cause damage to a patient's DNA, we may be able to help avoid secondary tumors caused by other treatments."

Too much MDM2 degrades p53

Normally, p53 halts the division of defective cells and forces them to commit suicide or lose the ability to reproduce. However, the tumor suppressor is disabled in many types of cancer, often because of gene mutations or defective signaling.

While mutations of the TP53 gene are rare in cancers of the blood, the p53 protein may be degraded by other factors, including high levels of MDM2, which binds to p53 and orchestrates its degradation.

Previous research has suggested that p53 activation by disrupting the binding of MDM2 to p53 may be a novel strategy for cancer therapy. In preclinical studies, small-molecule MDM2 antagonists called N
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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