The researchers describe the molecular mechanism of resistance to anti-androgen therapy for prostate cancer in an advance online publication in the December 21, 2003, issue of the journal Nature Medicine.

HHMI investigator Charles Sawyers at the University of California, Los Angeles, led the research. Sawyers collaborated on the studies with HHMI investigator Michael G. Rosenfeld at the University of California, San Diego. Co-lead authors were Charlie Chen and Derek Welsbie of Sawyers' laboratory. Another co-author on the paper is from the University of Washington in Seattle.

Sawyers and his colleagues were trying to understand why drug therapy for prostate cancer often fails despite early success. The current "gold standard" for treatment of prostate cancer consists of a drug regimen that lowers testosterone levels administered with "anti-androgen" drugs. These drugs compete for the binding site on the testosterone receptor proteins located in prostate-cancer cells. When testosterone activates these receptors, they, in turn, switch on internal cellular machinery that drives the growth of the tumors. "While drug therapy works in almost everyone for a period of time, usually measured in years, it stops working, despite the fact that patients continue to take the drugs," said Sawyers. "And that is why men die of this disease."

According to Sawyers, the tumor cells become "hormone-refractory," meaning they somehow "learn" to continue to proliferate even in the absence of the hormone, androgen, wh
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
21-Dec-2003