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Systematic analysis of gene family uncovers new therapeutic targets for colon cancer

Investigators from the Johns Hopkins Kimmel Cancer Center and Howard Hughes Medical Institute have completed what is believed to be the first systematic analysis of a disease-related gene family. Their analysis, reported in the May 9, 2003 issue of Science, uncovered gene mutations, linked to more than 30 percent of colon cancers, which could serve as therapeutic targets.

The research team studied 182 human colon cancers to identify mutations in the tyrosine kinase (TK) gene family. TK genes are thought be good therapeutic targets for managing cancer because the proteins they encode play key roles in controlling cell growth, differentiation, motility, and nearby tissue invasion. Although a few TK genes have been shown to be mutated in specific cancers, until now, no study has revealed how many or how often members of the TK gene family are altered in a particular cancer type, according to Victor E. Velculescu, M.D., Ph.D., assistant professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, who led the research effort.

"Our findings open the door to individualized analysis and treatment of colorectal cancer," says Velculescu.

TKs are so-called activating proteins that, when altered or damaged, signal cells to continually divide and take other actions that can lead to cancer. Drugs such as Gleevec, Herceptin and other inhibitor-class compounds that block the proteins made by mutated TK genes have been shown in both human clinical trials and animal studies to halt the cancer process.

"With this new work," Velculescu says, "one could imagine personalized therapeutics, based on mutations in different kinase genes and designed to match the mutated TK pathways present in each patient's particular tumor DNA."

To conduct this research, the investigators focused on the 138 normal TK genes that all humans contain. They were able to identify mutations in 14 of these genes only after si
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Contact: Valerie Matthews Mehl
mehlva@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
8-May-2003


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