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Researchers create first molecule blocks key component of cancer genes' on-off switch
Date:9/24/2010

BOSTONIn the quest to arrest the growth and spread of tumors, there have been many attempts to get cancer genes to ignore their internal instruction manual. In a new study, a team led by Dana-Farber Cancer Institute scientists has created the first molecule able to prevent cancer genes from "hearing" those instructions, stifling the cancer process at its root.

The study, published online by the journal Nature, demonstrates that proteins issuing stop and start commands to a cancer gene known as epigenetic "reader" proteins can be targeted for future cancer therapies. The research is particularly relevant to a rare but devastating cancer of children and young adults known as NUT midline carcinoma (NMC) a disease so obstinate that no potential therapy for it has ever reached the stage of being tested in a clinical trial.

"In recent years, it has become clear that being able to control gene activity in cancer manipulating which genes are 'on' or 'off' can be a high-impact approach to the disease," says the study's senior author, James Bradner, MD, of Dana-Farber. "If you can switch off a cancer cell's growth genes, the cell will die. Alternatively, switching on a tissue gene can cause a cancer cell to become a more normal tissue cell."

In this study, Bradner's lab synthesized a molecule that has both effects: by blocking a specific abnormal protein in NUT midline carcinoma cells, it stops them from dividing so prolifically and makes them 'forget' they're cancer cells and start appearing more like normal cells.

The assembled molecule affects the cell's multi-layered apparatus for controlling gene activity, a set of structures collectively known as the epigenome. Vast portions of each gene play a regulatory role, dictating whether the gene is active, busily sending orders for new proteins, or inactive, and temporarily at rest. The gene's DNA is packaged in a substance called chromatin, which is the slate on wh
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Contact: Teresa Herbert
teresa_herbert@dfci.harvard.edu
617-632-4090
Dana-Farber Cancer Institute
Source:Eurekalert

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