Drug Search Targets Liver Tumor Behavior

Cancer researchers combined advanced gene mapping techniques with innovative computer analysis to identify drugs to target and inhibit specific types of cancer cell behavior.

Specifically, investigators from Ohio State University (Columbus, USA) analyzed changes in gene activity that occurred when liver cancer cells began to spread into neighboring vascular tissue. They found that 47 genes were upregulated while 26 were downregulated. Armed with this information they screened databases of drug candidates searching for those that were known to inhibit any of the upregulated genes.

"This is an exciting new way to find potentially useful anticancer agents,” said senior author Dr. Tushar Patel, professor of internal medicine at Ohio State University. "For nearly two decades, cancer drug discovery has sought agents that block a single molecular target or pathway. Our approach identifies agents that could potentially block tumor progression by striking multiple genes that are associated with a particular cancer-related behavior.”

The investigators reported in the June 9, 2009, online edition of the journal Cancer that two compounds, resveratrol and 17-allylamino-geldanamycin (17-AAG) matched the criteria. Resveratol is a component of red wine that has been shown to inhibit the ability of liver cancer cells to invade tissues and metastasize, while 17-AAG has been found to have anticancer activity in some solid tumors but has not been tested in liver cancer.

"This approach is exciting because it can be applied to any well-defined disease behavior,” said Dr. Patel. "It might also improve the approach to drug discovery and design if some agents were modified to select for a particular genomic profile rather than a single chemical target. Overall, this could be a more relevant way of looking at cancer because we want to block certain disease changes and specific effects such as invasion, metastasis, or chemotherapy resistance.”

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