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Unusual three-drug combo inhibits growth of aggressive tumors

An experimental anti-cancer regimen combined a diuretic, a Parkinson's disease medication and a drug ordinarily used to reverse the effect of sedatives. The unusual mixture inhibited the growth of aggressive prostate tumors in laboratory mice in research conducted at Washington University School of Medicine in St. Louis.

Although their drug choices may seem capricious, the researchers weren't randomly pulling drugs from their shelves. They made their discovery using sophisticated methods for delving into the unique metabolism of cancer cells and then choosing compounds likely to interfere with their growth.

"This study, led by Joseph Ippolito, a very talented M.D./Ph.D. student, demonstrates the importance of looking at tumor metabolism," says senior author Jeffrey I. Gordon, M.D, director of the Center for Genome Sciences at the School of Medicine. "Using a broad array of technology, we've obtained a view of the tumor cells' metabolome (the set of small-molecule metabolites found within cells) and revealed aspects that were not expected and could be exploited."

The findings, published in a recent article in the Proceedings of the National Academy of Sciences, expand upon earlier work by the research group, which demonstrated that aggressive types of neuroendocrine tumors - seen in some types of lung, thyroid and prostate cancers - produce high amounts of a chemical called GABA, a neurotransmitter.

Because of the abundance of GABA in these tumors, the authors previously proposed that the chemical could potentially serve as a marker for poor-prognosis neuroendocrine tumors. But the latest findings also show that the techniques used to decipher the biochemistry of the tumors can effectively be applied to seek drugs that will affect tumor metabolism.

The techniques link DNA microarray technology - which can pinpoint highly active genes in the tumors - to precise measurements of abundant metabolites and their potential byp
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Contact: Gwen Ericson
ericsong@wustl.edu
314-286-0141
Washington University School of Medicine
7-Sep-2006


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