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CDK8 is Enough in Colorectal Cancer

Of the 11 known cyclin-dependent kinases, about half have long been the focus of cancer drug developers because they are involved in controlling cell-cycle progression, which goes into overdrive in cancer. However, none of the companies developing cyclin-dependent kinase inhibitors for cancer is specifically targeting cyclin-dependent kinase 8, a kinase that has been considered a player in transcription initiation but with minimal effects on the cell cycle.

Now, two papers in Natureoutline how cyclin-dependent kinase 8 (CDK8) controls a critical pathway in colorectal cancer that is unrelated to cell-cycle control.1,2 The findings open a new angle of attack that is downstream of epidermal growth factor receptor (EGFR), a target of approved antibodies against the cancer. Companies in the space now have good cause to re-examine CDK8 as a target, although this new role may require new compound-screening strategies and in vivoassays.

The studies were conducted by two independent groups at separate institutes associated with Harvard Medical School.

One team, led by William Hahn, associate professor of medicine at Dana-Farber Cancer Institute, came across CDK8 through RNAi knockdown screens for colon cancer cell proliferation genes. The other team, led by Nicholas Dyson, professor of medicine at the Massachusetts General Hospital Cancer

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