It activates p53 tumor-suppressor function without causing DNA damage
FRIDAY, March 7 (HealthDay News) -- A drug that targets a protein interaction involved in many types of cancer has been created by University of Michigan researchers.
In cell cultures, the small-molecule inhibitor MI-219 was highly effective at preventing the tumor-suppressor function of the protein p53 from being blocked in the presence of a protein called MDM2.
In animals with human cancer, MI-219 completely inhibited tumor growth and appeared to cause no severe side effects.
"For more than 10 years, scientists have searched for ways to block p53 inhibition, but with little success. Our study clearly shows that this can be done," study author Shaomeng Wang, a professor of medicine at the U-M Medical School and co-director of the molecular therapeutics program at the U-M Comprehensive Cancer Center, said in a prepared statement.
The research was published online this week in the Proceedings of the National Academy of Sciences.
Clinical trials of the drug could begin by the end of 2008. If the drug proves safe and effective in humans, it could potentially be used to treat many kinds of cancer, according to the researchers.
In almost all types of human cancer, p53 is inactivated. About half the time, this is because the protein MDM2 binds to p53 and inhibits the tumor-suppressor function of p53. In other cases, p53 dysfunction is due to a missing or mutated gene.
"Many traditional cancer drugs also activate p53, but they do so by causing DNA damage. They kill not only tumor cells but also normal cells, thus having severe side effects. MI-219 is unique in that it is designed to activate p53 without causing DNA damage, specifically killing tumor cells," Wang said.
The University of Michigan has filed a patent application for MI-219 and its related molecules. The technology has been licensed by Ascenta Therapeutics Inc., which helped fund the study. Wang is a scientific founder of Ascenta, serves as its chief scientific adviser, and is the principal investigator on a research contract from Ascenta to U-M.
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-- Robert Preidt
SOURCE: University of Michigan, news release, March 3, 2008
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