Why prostate hormone therapy temporary
Hormone deprivation therapy that prostate cancer patients often take gives them only a temporary fix, but U.S. researchers suggest why.
Jun Luo of Johns Hopkins University and colleagues at the University of Washington and Puget Sound VA Medical Center said they have discovered critical differences in the hormone receptors on prostate cancer cells in patients who no longer respond to this therapy.
Prostate cancer cells rely on androgens — male hormones that include testosterone — to survive and grow, Luo said. Since 1941, doctors have taken advantage of this dependency to battle prostate cancer by depriving patients of androgens, either by castration or chemical methods. For most, this hormone deprivation therapy causes tumors to shrink, sometimes dramatically. However, it’s never a cure — tumors eventually regrow into a stronger form, becoming resistant to this and other forms of treatment.
Using a large database, the researchers searched for variations of the nucleic acid RNA that prostate cells use to create androgen receptors. When they looked for these sequences in cells isolated from 124 prostate cancer patients, they found over-production of these outlaw variants in prostate cancer cells taken from patients whose disease had become resistant to hormone deprivation therapy.
Unlike cells with other androgen receptors, those with only AR-V7 receptors acted as if they were continually receiving androgens — turning on at least 20 genes that rely on androgens for activation — even though no androgens were present.
The findings are reported in the journal Cancer Research.