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Colon Cancer Oncogene Discovered
Date:9/14/2008

e didn't know about it," he said.

The second message involves the potential pharmacologic benefits of these results. CDK8 is a type of protein known as a kinase. Kinases are enzymes that catalyze the transfer of phosphate groups from one molecule to another. That action is like flipping a molecular switch, causing the recipient protein to turn on or off. It turns out that kinases tend to play key roles in the biochemical pathways that often go haywire in cancer, so they are popular targets for drug developers.

"There's a reasonable likelihood, though it hasn't happened yet, that one could develop a drug that targets this protein in colon cancer," he said, "and you could determine which colon cancer patients are likely to benefit."

That's because Hahn and his team showed, using a genetic technique called RNA interference, that knocking down CDK8 protein levels in cancer cells that normally contain elevated CDK8 levels, reduced cell proliferation. That effect was less pronounced in cells containing lower levels of CDK8.

So, those tumors with elevated CDK8 levels might make good candidates for novel drug therapies directed at the enzyme, Hahn said.

"This fits into an emerging concept in cancer treatment," he explained. "Not only do we develop better therapies, but hand-in-hand, we want to find which patients will respond to therapy, rather than giving it to everyone and hoping they will respond."

Brooks agreed that CDK8 is a potential drug target. He noted other potential benefits, too, such as possibly being able to identify those at elevated risk of developing colorectal cancer, or identifying those who should be screened earlier and more comprehensively. It may even be possible to develop chemopreventative compounds that could diminish the risk of developing cancer in the first place.

"But we are at the very beginning of that pathway," Brooks added. "All they have shown is this oncogene seems
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