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Researchers 'notch' a victory toward new kind of cancer drug
Date:11/11/2009

Scientists have devised an innovative way to disarm a key protein considered to be "undruggable," meaning that all previous efforts to develop a drug against it have failed. Their discovery, published in the November 12 issue of Nature, lays the foundation for a new kind of therapy aimed directly at a critical human protein one of a few thousand so-called transcription factors that could someday be used to treat a variety of diseases, especially multiple types of cancer.

"There is a pressing need for drugs that target transcription factors, both for use as scientific tools in the laboratory and as therapies in the clinic," said senior author James Bradner, a Harvard chemical biologist and oncologist at the Dana-Farber Cancer Institute and an associate member of the Broad Institute of MIT and Harvard. "Our work brings us a step closer toward that goal for a protein with major roles in cancer, cardiovascular disease and stem cell biology."

If human physiology is like a puppet show, then transcription factors pull the puppet strings. They bind to DNA and turn genes on or off, setting in motion genetic cascades that control how normal cells grow and develop. They also help maintain tumor growth, underscoring their importance as cancer drug targets. Yet transcription factors are counted among the most difficult molecules to neutralize with a drug in fact, no such drugs are currently available.

Based on his work as an oncologist, Bradner became deeply interested in a human protein called NOTCH. The gene encoding this protein is often damaged, or mutated, in patients with a form of blood cancer, known as T-ALL or T-cell acute lymphoblastic leukemia.

Abnormal NOTCH genes found in cancer patients remain in a state of constant activity, switched on all the time, which helps to drive the uncontrolled cell growth that fuels tumors. Similar abnormalities in NOTCH also underlie a variety of other cancers, including lung, ovaria
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Contact: Nicole Davis
ndavis@broadinstitute.org
617-714-7152
Broad Institute of MIT and Harvard
Source:Eurekalert

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