UPDATE - Issue 36 - Spring 2009
Why prostate cancer patients fail hormone therapy
The hormone deprivation therapy that prostate cancer patients often take gives them only a temporary fix, with tumours usually regaining their hold within a few years. Now, researchers at Johns Hopkins’ Medical Institute in the USA have discovered critical differences in the hormone receptors on prostate cancer cells in patients who no longer respond to this therapy. The findings, reported in the January issue of Cancer Research, could lead to a way to track disease progression, as well as suggesting new targets to fight prostate cancer.
Prostate cancer cells rely on androgens, male hormones that include testosterone, to survive and grow. For many years, doctors have taken advantage of this dependency to combat the disease 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 is 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, the researchers looked to a key player: the androgen receptors on prostate cancer cells.
Using a large database, the researchers led by Jun Luo, an assistant professor at Johns Hopkins’, searched for variations of the nucleic acid RNA that prostate cells use to create androgen receptors. Eventually they identified 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.
Luo believes that we may eventually be able to develop an assay to test for these androgen receptor variants, giving us a way to test which patients are good candidates for hormone deprivation therapy and providing a way to monitor disease progression in patients already on this therapy.
One of these seven variant sequences, 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 in patients already on this therapy.
Examining the differences between these androgen receptor variants, particularly AR-V7, and normal receptors may provide researchers with new ideas forming a basis from which to develop prostate cancer-fighting pharmaceuticals.