New drug shows promise in treating drug-resistant prost...( A new therapy for metastatic prostat...)

A new therapy for metastatic prostate cancer has shown considerable promise in early clinical trials involving patients whose disease has become resistant to current drugs.

Chemists and biologists at UCLA and colleagues at several other institutions, including Memorial Sloan-Kettering Cancer Center, have created a new drug to treat a particularly lethal form of the disease, known as castration-resistant prostate cancer, or CRPC. Also referred to as hormone-refractory prostate cancer, CRPC is resistant to further treatment by anti-hormone drugs such as Casodex and Eulexin.

In an article published April 9 in the advanced online edition of the journal Science, the scientists describe the development and testing of two novel compounds, MDV3100 and RD162, which block the androgen receptor (AR) in CRPC cells, and report results from clinical trials in which MDV3100 was found to lower prostate-specific antigen (PSA) levels a marker for tumor growth in men with CRPC.

The new, small organic molecule MDV3100 was "designed as a very strong antagonist of the androgen receptor to stop the growth of any prostate cancer that requires the AR for propagation, which includes most forms of prostate cancer," said Michael Jung, UCLA professor of chemistry and biochemistry and a researcher at UCLA's Jonsson Comprehensive Cancer Center, whose research group synthesized both MDV3100 and RD162.

The biology research was carried out in the UCLA departments of medicine, urology and pharmacology by Charles Sawyers and his research group; Sawyers has since moved to Memorial Sloan-Kettering Cancer Center in New York, where he serves as chair of the human oncology and pathogenesis program. The UCLA patents for both compounds were licensed by the pharmaceutical company Medivation Inc., which chose to test MDV3100 in clinical trials.

The drug has successfully completed Phase 1 and Phase 2 clinical trials, and the Food and Drug Ad
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