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Mar. 6, 2002 |
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Study shows how prostate cancer resists hormone therapy SAN FRANCISCO -- Mar. 6, 2002 (Cancer Digest) -- A new study shows that the reason men with advanced prostate cancer don't respond to hormone therapy is because the cancer cells have shut down the genes that produce the protein receptors for the drugs. Hormone therapy is often used to treat prostate cancer but these drugs that mimic the effects of estrogen do not work on many late-stage cancers. Now researchers say they can explain the failure of these drugs, and suggest a way to restore their potency. The research team led by Dr. Raj Dahiya, director of the urology research center at San Francisco Veterans Medical Center, found that the genes needed for cells to respond to estrogen are switched off by a process called hypermethylation. This is a well-known process in which numerous groups of a methyl compound are attached to stretches of DNA near the beginning of a gene. This effectively blocks the process whereby the gene is split open and the code to make its protein is read. "This hypermethylation explains why we see inactivation of estrogen receptors in prostate cancer, and why hormone therapy no longer works in many cases," said Dahiya, in a prepared statement. The researchers examined prostate tissue taken from 38 prostate cancer patients and found that nearly all tissue samples from tumors had hypermethylation on their estrogen receptor genes, but tissue samples from healthy sections of the prostate showed no such methylation. The Veterans Administration and National Institutes of Health-funded study appears in this week's issue of the Journal of the National Cancer Institute. In it, Dahiya's group first showed that normal prostate cells were free of methylation at estrogen receptor genes and the cells displayed plenty of estrogen receptors. Cells taken from an early stage prostate cancer, however had some methylation, which resulted in relatively few estrogen receptors, but cells examined from late-stage prostate cancers exhibited high levels of methyl or hypermethylation at the site of estrogen receptor genes resulting in no estrogen receptors on the cell surface. Genetics researchers have studied hypermethylation for years, said Dahiya, who is also professor of urology at the University of San Francisco, and they know how to prevent it. This raises the hope that tumors resistant to hormone therapy could be made responsive again. Dahiya and his colleagues treated some of their prostate cancer cells growing in a laboratory dish with a drug that reverses methylation, and the cells once again switched on their estrogen receptor genes. "People are testing de-methylating agents in clinical trials for several other cancers. In prostate cancer we could inject these drugs directly into the prostate, and that might restore the lost effectiveness of hormone therapy," he said. |
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