Gene copying aids prostate tumor growth.

Even severe prostate tumors usually shrink after an initial treatment with drugs. Yet many of these cancers advance again, resisting all attempts to rein them in.

Until now, nobody knew why. But a report published this month suggests that some prostate tumors may outwit therapy by generating extra copies of a gene that promotes cell growth. Recurrence of tumors greatly increases the risk of dying.

The prostate gland, the walnut-size male sex gland located below the bladder, produces some of the fluid that goes into semen. The American Cancer Society estimates that more than 40,000 men in the United States will die of prostate cancer this year.

For men with advanced prostate cancer, doctors recommend drugs or surgical removal of the testes to stanch the flow of androgens, the male sex hormones, including testosterone, that fuel the growth of malignant prostate cells.

That strategy can work for months or even years. But if the cancer springs back, it does so despite hormone-blocking therapy.

Tapio Visakorpi of the National Center for Human Genome Research in Bethesda, Md., and a team of U.S. and Finnish colleagues wanted to find out how that deadly resistance works.

They started their experiment by analyzing 23 recurrent prostate tumors taken from men who had been treated with hormone-blocking therapy. The research team discovered that 7 of 23 tumors (30 percent) had extra copies of a gene known as the androgen receptor gene. This gene codes for a protein receptor that interacts with androgens and somehow tells prostate cells to divide.

On average, tumor cells in the study contained from 4 to 22 androgen receptor genes. In one case, a tumor cell had 40 receptor genes. Healthy prostate cells contain only one such gene, which resides on the X chromosome.

The gene copying appears to take place as a result of treatment: When the team looked at 16 prostate tumor samples taken from the same patients prior to therapy, they found no such gene amplification. Visakorpi and his coworkers describe their findings in the April Nature Genetics.

The findings indicate that some prostate tumors may adapt to, or even thrive in, the environment created by hormone-blocking therapy. Such treatment curbs the body's supply of androgens by targeting the testes' production of these hormones. The adrenal glands still secrete a small amount, however.

In response to the decreased androgen production, tumor cells multiply the androgen receptor gene. Such malignant cells probably crank out lots of the gene's protein product and thus can efficiently make use of even low concentrations of androgen, Visakorpi speculates.

"I think it's an exciting result," comments oncologist Rosalind Eeles of the Institute of Cancer Research & Royal Marsden Hospital in London, England. If confirmed by other studies, the findings suggest new treatment avenues for men who have recurrent prostate tumors. At present, doctors give such patients standard doses of hormone-blocking therapy, says Eeles. But the new study suggests that oncologists should increase the dose--if it can be done safely --thus creating a more effective androgen blockade, she says.

The findings may also lead to better treatment for men with newly diagnosed prostate cancer, Visakorpi says. If researchers could identify those tumors most likely to copy the androgen receptor gene, oncologists might start off with a therapy aimed at complete blockage of androgen.

That drastic approach just might stop prostate cancer in its tracks, he adds.