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Tiny molecules have big potential as cancer drugs, Stanford researcher believes

PHILADELPHIA Many cancer therapies take a "big stick" approach, targeting rapidly dividing cells in the body to stop malignancies in their tracks but often triggering horrible side effects in the process. New research from the Stanford University School of Medicine points toward the possibility of a different type of cancer drug small molecules that would home in on the proteins tumors need without poisoning patients.

Matthew Bogyo, PhD, assistant professor of pathology, will discuss his studies of some of these molecules at an Aug. 24 talk during the "Genomic Approaches to Enzymology" session of the American Chemical Society's national meeting in Philadelphia.

Previous studies have shown that an increase of certain proteins, called cathepsin cysteine proteases, is associated with tumor development. "People have shown that more of the cathepsins are present in cancers and that they appear to be secreted by cancer cells," said Bogyo. "The question is what are they doing and does it help to block them?" To find out, Bogyo and colleagues used fluorescent tags to track cathepsin activity in mouse models of two types of cancer. They found the cathepsins helped build blood vessels to the tumors as well as increase tumor growth and invasiveness.

The team also tried giving a broad-spectrum cathepsin inhibitor to some cancerous mice and found that it slowed tumor development both in early and late stages of growth with no apparent side effects. The National Cancer Institute has since fast-tracked the inhibitor into studies of toxicity and pharmacodynamics as a potential drug. Meanwhile the research group has used the compound as a jumping-off point, testing similar compounds to find those that bind specifically to "problem" cathepsins, instead of to all of them. Bogyo is also looking for additional molecules that have better potency and pharmacodynamic properties.

Bogyo will give details on tests of some of these molecules at his presentatio
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Contact: Mitzi Baker
mitzibaker@stanford.edu
650-725-2106
Stanford University Medical Center
24-Aug-2004


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