THURSDAY, Nov. 7, 2002 (HealthDayNews) -- A family of drugs that men with advanced prostate cancer take to suppress their disease may, after time, promote cancer cell production.
The medications are called anti-androgens, say researchers at the University of Rochester.
The discovery of this unwelcome side effect is of more value to scientists than to prostate cancer patients -- at least for now. The reason: Anti-androgens are currently one of the most effective treatments for men with advanced prostate cancer, says University of Rochester urologist Dr. Edward Messing.
"It is a big finding from a biological point of view, but from a clinical point of view, while it could be potentially beneficial, more work has to be done," Messing says.
The standard treatment for men with advanced prostate cancer -- defined as the spread of the cancer beyond the prostate gland -- is to take anti-androgens. These drugs block the production of the male hormone testosterone, which prostate cancer cells need to grow. Without the hormone, the cancer cells die, the researchers say.
Doctors have long known that for some reason, the cancer-suppressing effect of anti-androgens stops after a period of time, usually between 18 to 24 months. The patients' cancer then reappears.
The researchers at the University of Rochester's George Whipple Laboratory for Cancer Research have found that anti-androgens, while suppressing testosterone production, also activate a molecule known to cause cancerous cells to grow.
"We never thought this drug had a second role," says Chawnshang Chang, a urology professor who headed the research. "It suppresses the androgen, but also activates a molecule known as MAP kinase that has been linked to tumor growth."
Chang says the anti-androgen drugs, like hydroxyflutamide, successfully block testosterone production by suppressing the protein that acts as an androgen receptor. But the researchers found that, after time, as testosterone production declines, MAP kinase activation becomes more pronounced.
"We don't know the mechanism for this," he says. "We know the outcome, but not the mechanism."
The Rochester researchers' finding, which earned an award for outstanding research from the American Urological Association, is described in the new issue of Cancer Research.
There are about 2.8 million cases of prostate cancer diagnosed annually in the United States, and 30,000 deaths a year from the disease, according to National Vital Statistics reports. There has been intensive research into the causes of and potential cures for the disease.
Chang has long been interested in discovering why the anti-androgens eventually lose their power to combat the cancer.
He and his colleagues studied cancer cells from four men with advanced prostate cancer, comparing cells from early in their disease to cells after the anti-androgen therapy became ineffective. They found that the levels of the molecule MAP kinase were much higher in the cells of the men after they had had the hormone therapy.
"Before taking the drug, the levels were really low. Afterwards the levels were really high," Chang says.
Messing, who worked with Chang on the findings, says, they "found that cells that had no androgen in them at all were still replicating. The hydroxyflutamides can turn on signals that eventually make the cells divide in the absence of the androgen receptor."
Chang says the finding should spur drug companies to create new types of anti-androgen drugs that don't activate the MAP kinase molecule, or to perhaps combine the existing anti-androgen drugs with another drug that might suppress the MAP kinase molecule.
But for now, he says, "There is no good drug available."
Dr. Edward Gelmann, professor of oncology at the Georgetown University Medical Center's Lombardi Cancer Center, says there are experimental drugs that could be used to thwart the MAP kinase molecule.
"There are no [such medicines] in clinical trials, but there are experimental medicines," he says.
In the meantime, Messing says, the new findings should prod doctors to carefully monitor their prostate cancer patients to determine when the anti-androgen drugs may no longer be suppressing androgen, but activating the MAP kinase molecule. A good measure is a blood test called the PSA count, which gauges levels of prostate specific antigen.
"When the PSA goes up, don't wait to stop the drug," Messing says.
This is already the clinical strategy, Gelmann says. "We do that anyway."
What To Do
For more information on the prostate gland, visit the Agency for Healthcare Research and Policy. The American Cancer Society has information on early diagnosis of prostate cancer.
