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Unconventional hunt for new cancer targets leads to a powerful drug candidate for leukemia
Date:8/3/2011

Cold Spring Harbor, N.Y. Scientists at Cold Spring Harbor Laboratory (CSHL) and five other institutions have used an unconventional approach to cancer drug discovery to identify a new potential treatment for acute myeloid leukemia (AML). As reported in Nature online on August 3, the scientists have pinpointed a protein called Brd4 as a novel drug target for AML, an aggressive blood cancer that is currently incurable in 70% of patients. Using a drug compound that inhibits the activity of Brd4, the scientists were able to suppress the disease in experimental models.

"The drug candidate not only displays remarkable anti-leukemia activity in aggressive disease models and against cells derived from patients with diverse, genetic subtypes of AML, but is also minimally toxic to non-cancerous cells," says CSHL scientist Chris Vakoc, M.D., Ph.D., who led the team. "The drug is currently being developed for therapeutic use for cancer patients by Tensha Therapeutics and is expected to enter clinical trials within two years."

The protein target identified in the RNAi screen described in the current study, Brd4which contains a distinct domain or region known as a bromodomainis a member of the BET family of proteins, which help regulate gene expression. By "reading" certain epigenetic marks or chemical tags attached to chromatinthe combined package of DNA and proteins around which it is coiled within the cell's nucleusBrd4 helps control the pattern of which genes are switched on and how they work.

"Cancer is clearly a genetic disease, but we also appreciate that epigenetic changes in how genes are expressed contribute to the uncontrolled growth of cancer cells," says Vakoc. Cancer cells exploit this altered epigenetic landscape to drive their cell-growth programs.

Vakoc and other scientists have seized on the idea of interfering with this epigenetic dependency to turn the tables on cancer. "Epigenetic alterations acquired during
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Contact: Hema Bashyam
bashyam@cshl.edu
516-367-6822
Cold Spring Harbor Laboratory
Source:Eurekalert

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