Testosterone May Fight as Well as Feed Prostate Cancers

In a surprising finding that suggests radical changes in the wayprostate cancer is managed, researchers at the University of ChicagoMedical Center have shown in laboratory experiments that the malehormone testosterone, which fuels prostate cancers early in theirgrowth, can in later stages cause tumors to stop growing or evenshrink.

The finding is reported in the October 15 issue of the Proceedingsof the National Academy of Sciences.

Doctors have routinely used surgical or chemical castration toslow the growth of cancer that has spread beyond the gland since1941, when University of Chicago urologist Charles Huggins showedthat prostate cancers require testosterone for growth and demonstratedthe effectiveness of removing the hormone. Huggins received theNobel Prize for this work in 1966.

Men treated with antihormone therapy often show dramatic improvement.But within a few years, the tumors regrow because the cells losetheir dependency on testosterone and are able to thrive withoutit.

Now a researcher who was a colleague of Huggins for more than30 years has shown that those tumors that no longer depend ontestosterone may, in fact, be sensitive to it. Shutsung Liao,phd, professor in the Ben May Institute for Cancer Research, andcoworkers showed in laboratory mice that testosterone can shrinkexperimental human prostate tumors that no longer depend on thehormone.

The finding suggests that testosterone supplementation, perhapsdelivered by a patch, may be beneficial for certain types of prostatecancer, and that prolonged use of antihormone drugs, like leuprolide(Lupron), goserelin (Zoladex), and finasterid (Proscar) shouldno longer be routine.

Interesting Preliminary Finding

"This is an interesting preliminary finding that may makeus rethink our approach to therapy," said Glenn Gerber, md,a University of Chicago urologist not connected to the study.

Prostate cancer is the most commonly diagnosed cancer in Americanmen, with 317,000 new cases and 41,400 deaths expected in 1996.Although several treatment options are available for cancers confinedto the gland, only antihormone therapy has been effective forslowing the growth of distant tumors.

"Although three-quarters of prostate cancer patients canhave their tumors shrunk by castration or anti-hormone drug therapy,most of these cancers recur in 1 to 3 years and are then no longerdependent on hormones," Liao said. "Currently, oncethe tumor becomes independent of testosterone, there is no wayto treat it."

Standard chemotherapy agents are not very effective against prostatecancer. The goal, according to Gerber, is to improve long-termmanagement of the disease.

"While this new approach is not likely to cure anyone,"said Gerber, "it suggests that we may be able to restartthe survival clock, perhaps several times, not just by starvingcells that need testosterone but also by feeding it to cells thatgag on it."

To simulate the recurrence of hormone-independent cancer, researchassociate John Kokontis grew human prostate cancer cells in thelaboratory and weaned them off testosterone, a process that requiredrepeated re-culturing of the cells over a 2-year period. Thesecells, now capable of growing testosterone-free, were used toseed tumors in laboratory mice. The researchers looked at theeffect of testosterone on these mice compared to mice implantedwith tumors that need testosterone.

The researchers found that adding even low levels of testosteronecould shrink established tumors of hormone-independent cells.Removing the added testosterone, or adding testosterone-loweringdrugs, caused the tumors to regrow.

The researchers dedicated the report to Huggins, who turned 95last month and has been in ill health. The work was funded bythe National Institutes of Health.

Authors of the report in addition to Liao and Kokontis are visitingprofessor Yoshihisa Umekita and senior research associate RichardHiipakka.