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Experimental drug shown to block mutant protein causing blood disease

BOSTON--Scientists at Dana-Farber Cancer Institute and Brigham and Women's Hospital have prolonged the lives of mice with a rare blood disorder by using an experimental drug that blocks signals promoting runaway growth of blood cells.

The researchers also tested the drug, PKC412, in a patient with the hard-to-treat disease, called Myeloproliferative Disease (MPD), and saw her symptoms improve.

PKC412, like the spotlight drug Gleevec, is a highly specific "targeted" drug that disables a switch in cancer cells that has become jammed in the "on" position because of a genetic mutation. The glitch allows a continuous stream of signals to prod blood cells into an uncontrolled frenzy of division and growth. The overproduction of white blood cells in MPD damages organs and generally turns into an acute leukemia that can be fatal.

The report appears in this week's Online Early Edition of the Proceedings of the National Academy of Sciences. Jing Chen, PhD, of Brigham and Women's, and Daniel J. DeAngelo, MD, PhD, of Dana-Farber, are the paper's co-first authors. D. Gary Gilliland, MD, PhD, a Howard Hughes Medical Institute investigator at Brigham and Women's Hospital, and Richard M. Stone, MD, of Dana-Farber are the senior authors. Other authors are from Dana-Farber, Brigham and Women's, Harvard Medical School, Emory University, and Novartis Pharma AG.

"The study shows the potential utility of drugs that block mutant tyrosine kinases, and that these drugs are opening more doors to treating cancers," explains Stone.

Tyrosine kinases are molecules that act as biological switches inside cells, regulating processes including cell division and growth. Abnormal kinases have been discovered to be major culprits in many forms of cancer. Because inhibitor drugs strike the abnormal kinases in cancer cells without harming normal tissue, they are associated with fewer side effects than standard cancer drugs.

In the study, mice with MP
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Contact: Bill Schaller or Richard Saltus
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
21-Sep-2004


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