Hormones commonly used to treat advanced stages of prostate cancer can eventually help the cancer grow, offering the first explanation of why hormone therapy almost always fails after two to three years, according to a study published this week in the Proceedings of the National Academy of Sciences.
Researchers at the University of Rochester Cancer Center found that the drugs used to block the supply of androgens--natural steroid hormones such as testosterone that signal prostate cancer cells to grow and multiply--can actually begin mimicking the very hormones they are supposed to stop.
The switch, observed in lab-grown prostate tumors, occurs when a protein molecule in the prostate cancer cells, called ARA70, binds with an androgen receptor, said lead investigator Chawnshang Chang, a professor of pathology and urology at the University of Rochester. This interaction somehow induces the anti-androgen drugs to stimulate the hormone receptors rather than block them.
"Once these two proteins interact, the anti-androgens start behaving like androgens," Chang said.
Testosterone makes up 98% of androgens feeding the cells. Intervention typically involves surgical or medical castration, the latter using chemicals to prevent the body from making testosterone.
Anti-androgen drugs such as bicalutamide and flutamide, also known by their respective brand names Casodex and Eulexin, are then used to block the remaining androgens produced by the adrenal glands that lie on top of the kidneys.
One of the mysteries that has long puzzled clinicians is why androgen levels and cancer tumors, after years of shrinking with anti-androgen drugs, suddenly start growing again. Dr. Arie Belldegrun, professor of urology and chief of the division of urologic oncology at the UCLA Johnsson Cancer Center, said the study helps explain this mystery. He also said the findings could be used to help develop more effective drugs.
"Once you know that this molecule is the problem, you can design blockers that block ARA70," he said. "You can focus on something more specific."
Prostate cancer is the leading form of cancer among men in the United States. Every year, nearly 40,000 die from prostate cancer, making it the No. 2 cause of cancer death in the nation. Hormone therapy is one of the last lines of defense for prostate cancer patients, used only when the disease has spread to other parts of the body.
"At least a third of all patients, maybe even half, diagnosed every year will get this therapy," said Belldegrun.
Chang cautions that prostate cancer patients should not stop hormone therapy because the findings are limited to cell cultures in the laboratory and tests on animals or humans are still to come. He adds that there is still "no better method" available for treating the advanced stages of prostate cancer, and that it is at least effective for the first few years of treatment.