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...experimental drug for advanced prostate cancer has shown preliminary success in the first and second phases of clinical trials, shrinking tumors in the lab and reducing signs of the disease in patients with drug-resistant cancer, according to a report published in the April 10 issue of the journal Science...
...Science paper, co-authored by Sawyers and other researchers at HHMI, the University of California, Los Angeles, and a host of other institutions, data suggest that a new chemical compound may sidestep the problem of resistance. When used to treat mouse tumors that were derived from drug-resistant prostate-cancer cells, the compound led to dramatic shrinkage, which has researchers hoping for a similar effect in humans. "The compounds are working extremely well in our models," says Sawyers. "We think this might be able to deal with the resistance question." (Read "Prostate Exams: When Are They Necessary...
...Researchers in Sawyers' lab began with a chemical that showed promise in attaching to the androgen receptor on cancer cells. Then the scientists, like composers writing variations on a theme, synthesized nearly 200 versions of the drug and screened each one on prostate-cancer cells that had been engineered to be drug-resistant. In the end, two molecules - RD162 and MDV3100 - fit the experimental criteria, binding to the receptor site without stimulating cancer-cell growth. Both chemical compounds were then tested in mice. "They caused the tumors to shrink significantly," says Sawyers...
...drug company Medivation, for which Sawyers is a paid consultant, chose MDV3100 to test in a clinical trial. In initial studies, 30 patients who had drug-resistant prostate cancer were given doses of MDV3100. Twenty-two showed a sustained reduction in their blood levels of prostate-specific antigen, or PSA, a protein that is elevated in the presence of prostate cancer; in 13 of those 22, the decline was more than 50%. That Phase 2 trial is ongoing, but the drug has shown enough promise to prompt the Food and Drug Administration to grant Medivation permission for a large-scale...
...That trial - needed before MDV3100 can be approved for use in humans - will take several years. In the meantime, there are still questions to be explored, including why the drug had little effect in eight of the subjects in the early clinical trial. Sawyers' team is working on an answer. It's possible that the drug may have to be given in larger doses to some patients or that some prostate cancers may mutate to the point where antiandrogen drugs are simply ineffective. "There could be changes that are preventing the drug from binding," he says...