smart weapon. A new compound that clogs the androgen receptor tumors decreased prostate cancer drug resistant mice ( bottom line , tumors after 5 days).
C. Tran et al. Science
For the unlucky 10% of men diagnosed with prostate cancer who have the most aggressive form, the prognosis is poor. The drugs available against prostate cancer can first reduce their tumors, but the remaining cancer cells usually grow out of control again after some years. These cases resistant to drugs account for most of the nearly 29,000 annual deaths in the US from prostate cancer.
Researchers led by Charles Sawyers at Memorial Sloan Kettering Cancer Center in New York have now developed a compound that could prevent some deaths. This Thursday they will report online Science that in mice the compound decreased tumor implanted human prostate untreatable with existing drugs and that he had evidence to arrest tumor growth in the men with a similar drug resistant cancer. Although more clinical studies are required, cancer researchers are excited about the potential drug, which treats prostate cancer by a different mechanism than existing drugs. "It may be a new and better way to treat prostate cancer," said oncologist Philip Kantoff of the Dana-Farber Cancer Institute in Boston.
In prostate cancer, genetic changes in cells allow testosterone and similar hormones, called androgens, to feed the rampant cell growth. most patients receive drugs to limit the production of androgen body. If the tumor continues to grow, doctors prescribe other drugs which bind to the androgen receptor in the cytoplasm of the cell of the prostate, so that the hormone can not land on the receptor and activate it. But these drugs usually fail after a time.
This problem intrigued Sawyers, who had previously worked on resistance to Gleevec, a drug against leukemia powerful, he helped to develop. in 03, the team of Sawyers showed why tumor cells advanced prostate possibly counteract the standard drugs: the cells produce high levels of androgen receptor, which makes them so sensitive that even androgen drugs blocking the receptors can stimulate cells to grow. Next Sawyers joined forces with chemist Michael Jung, whose group at the University of California, Los Angeles, synthesized nearly 0 androgen-like compounds. The researchers selected molecules, selecting those that bind tightly to the androgen receptor but does not activate. The group of Jung then twisted two promising candidates for potential drugs.
In addition to binding to the androgen receptor, the new compounds appear to prevent it from entering the nucleus of the cell, the DNA binding, and initiation of gene expression, the The team reports. "It's a great story," says pharmacologist at Duke University's Donald McDonnell cancer in Durham, North Carolina
In a clinical study with one of the compounds, dubbed MDV3100, levels of prostate specific antigen -. a marker for the tumor growth of prostate - decreased by at least 50% in 13 of 30 patients with advanced disease for whom other treatments have failed "in this group. of patients, this result is very impressive, "said Sawyers. Medivation Inc. in San Francisco, California, who collaborated on this work is currently testing the drug at higher doses on more patients. (Sawyers is a consultant for the company and is a co-inventor on a patent for MDV3100.)
Although MDV3100 extends the life of men with advanced prostate cancer, their tumors are likely to become resistant to him too . But researchers hope that the compound may be combined with another drug candidate, developed by a different team, but in the tests, which stops cancer cells from making their own supply of androgens. "A very exciting possibility" is that a cocktail of these drugs will prevent men with cancer of early prostate never reach the stage drug resistant, says Kantoff, who heads one of the many centers that test MDV3100.
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