WASHINGTON - Hormone deprivation therapy in prostate cancer only provides temporary relief, with tumours usually regaining their hold within a couple of years. Now, researchers have discovered critical differences in the hormone receptors on prostate cancer cells in patients who no longer respond to this therapy. The findings could open a way to track disease progression.
Prostate cancer cells rely on androgens, male hormones that include testosterone, to survive and grow, explained Jun Luo, assistant professor at Johns Hopkins’ James Buchanan Brady Urological Institute.
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 patients, this hormone deprivation therapy causes tumours to shrink, sometimes dramatically. However, it’s never a cure. Tumours eventually regrow into a stronger form, becoming resistant to this and other forms of treatment.
Seeking the reason why this therapy eventually fails, Luo and his colleagues at the Johns Hopkins University School of Medicine, University of Washington and Puget Sound VA Medical Centre looked to a key player: the androgen receptors on prostate cancer cells.
Using a large database, researchers searched for variations of the nucleic acid RNA that prostate cells use to create androgen receptors, eventually identifying seven RNA sequences different from the ‘normal’ androgen receptor already known to scientists.
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.
One variation, known as AR-V7, was also prevalent in a select group of patients who had never taken hormone therapy, but whose cancer aggressively regrew after surgery to remove their tumours, said a Johns Hopkins release.
The results suggest that hormone therapy might encourage prostate cancer cells to overproduce the AR-V7 receptors over time, leading them to survive and grow aggressively even without androgens, explained Luo.
These findings appeared in Thursday’s issue of Cancer Research.