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Dana-Farber Cancer Institute
Scientists at the Dana-Farber Cancer Institute, Boston, Massachusetts, have linked the CDK8 gene to colon cancer, a previously unsuspected association. Recent findings were published in an advanced online issue of Nature
. According to senior author William Hahn, MD, PhD, associate professor of medicine, Harvard Medical School, the research advance was made possible by using new tools designed to assess the activity of specific genes. The Dana-Farber study team suggested that as these tools are improved, the stream of newly discovered cancer genes will likely increase, providing new avenues for therapy.
The study first focused on the protein beta-catenin, a transcription factor that is overactive in nearly all colorectal cancers. Although overactive beta-catenin plays a role in the initial formation of tumors, other genetic abnormalities must transpire for tumors to become fully malignant.
To determine which genes control the production of beta-catenin and which are involved in the proliferation of colon cancer cells, the research team ran 3 screening tests. In the first 2, they used RNA interference to shut down more than 1000 genes, one by one, and recorded the instances where beta-catenin activity decreased and the cells stopped growing. Next, they analyzed colon cancers for genes that had extra copies.
When they looked at overlap in the results of the 3 tests, the CDK8 gene stood out. The protein produced from CDK8 is part of the mediator complex, a conglomeration of proteins that serves as a bridge for compounds involved in gene transcription. “This study demonstrates that blocking CDK8 interferes with the proliferation of colon cancer cells that have high levels of the CDK8 protein and overactive beta-catenin,” stated Dr. Hahn. “Drugs that target CDK8 may be very useful against tumors whose growth is driven by beta-catenin.”
Speaking in broader terms about the implications of the research, Dr. Hahn concluded, “This study provides confirmation that many of the genes involved in cancer have yet to be identified. When it comes to identifying gene targets for therapy, we've really only scratched the surface.”
The study is noteworthy in another respect, as well. Many of the abnormal proteins linked to cancer are known as transcription factors because they are able to “read” cell DNA and use that information to produce other cell proteins. Although transcription factors are important regulators, this class of proteins has proven impossible to target with drug therapy. Genes like CDK8, which influence transcription factors, make attractive targets for drugs because they may be able to disrupt the cancer process and disable tumor cells.