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St. Jude Study Finds Treatment With New Drug Might Make Tumor Cells More Sensitive to Therapy
Date:9/16/2008

Study shows treatment with a newly discovered drug could be useful in sensitizing tumor cells to therapeutic irradiation and potentially some chemotherapies

MEMPHIS, Tenn., Sept. 16 /PRNewswire-USNewswire/ -- Scientists at St. Jude Children's Research Hospital have shown that it might be possible to make tumor cells more sensitive to irradiation and some types of chemotherapy by treating them with a drug that cripples their ability to repair DNA damage caused by these therapies.

The St. Jude researchers demonstrated in the laboratory that a molecule called CP466722 rapidly blocks the ATM protein's ability to orchestrate a series of biochemical events that culminate in the repair of DNA damaged by irradiation. The molecule exerted its effect in small quantities, and its effects rapidly ended after it was removed from cells, suggesting that such a treatment in humans would not have significant or long-term side effects, the researchers said.

Results of the study were published in the Sept. 15 issue of the journal Cancer Research.

ATM plays a critical role in repairing a type of DNA damage called double-strand breaks, in which each of the two strands making up this molecule are cut, according to Michael Kastan, M.D., Ph.D., director of the St. Jude Comprehensive Cancer Center. This process protects cells from the potentially lethal or mutation-causing effects of free oxygen radicals and irradiation--both of which routinely threaten them, he added. Kastan is senior author of the report on these findings.

Children lacking the gene for ATM develop ataxia-teleangiectasia, a disease that causes several debilitating problems, such as neurodegeneration, cancer and sensitivity to irradiation that leads to irreparable, double-stranded DNA breaks.

"We found that inhibition of ATM activity with CP466722 produces cellular effects that are identical to those seen in cells that lack ATM," Kastan said. "It's as if we temporarily turn
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SOURCE St. Jude Children's Research Hospital
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