In a surprising finding that suggests radical changes in the way
prostate cancer is managed, researchers at the University of Chicago
Medical Center have shown in laboratory experiments that the male
hormone testosterone, which fuels prostate cancers early in their
growth, can in later stages cause tumors to stop growing or even
The finding is reported in the October 15 issue of the Proceedings
of the National Academy of Sciences.
Doctors have routinely used surgical or chemical castration to
slow the growth of cancer that has spread beyond the gland since
1941, when University of Chicago urologist Charles Huggins showed
that prostate cancers require testosterone for growth and demonstrated
the effectiveness of removing the hormone. Huggins received the
Nobel 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 lose
their dependency on testosterone and are able to thrive without
Now a researcher who was a colleague of Huggins for more than
30 years has shown that those tumors that no longer depend on
testosterone may, in fact, be sensitive to it. Shutsung Liao,
phd, professor in the Ben May Institute for Cancer Research, and
coworkers showed in laboratory mice that testosterone can shrink
experimental human prostate tumors that no longer depend on the
The finding suggests that testosterone supplementation, perhaps
delivered by a patch, may be beneficial for certain types of prostate
cancer, and that prolonged use of antihormone drugs, like leuprolide
(Lupron), goserelin (Zoladex), and finasterid (Proscar) should
no longer be routine.
Interesting Preliminary Finding
"This is an interesting preliminary finding that may make
us 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 American
men, with 317,000 new cases and 41,400 deaths expected in 1996.
Although several treatment options are available for cancers confined
to the gland, only antihormone therapy has been effective for
slowing the growth of distant tumors.
"Although three-quarters of prostate cancer patients can
have their tumors shrunk by castration or anti-hormone drug therapy,
most of these cancers recur in 1 to 3 years and are then no longer
dependent on hormones," Liao said. "Currently, once
the tumor becomes independent of testosterone, there is no way
to treat it."
Standard chemotherapy agents are not very effective against prostate
cancer. The goal, according to Gerber, is to improve long-term
management of the disease.
"While this new approach is not likely to cure anyone,"
said Gerber, "it suggests that we may be able to restart
the survival clock, perhaps several times, not just by starving
cells that need testosterone but also by feeding it to cells that
gag on it."
To simulate the recurrence of hormone-independent cancer, research
associate John Kokontis grew human prostate cancer cells in the
laboratory and weaned them off testosterone, a process that required
repeated re-culturing of the cells over a 2-year period. These
cells, now capable of growing testosterone-free, were used to
seed tumors in laboratory mice. The researchers looked at the
effect of testosterone on these mice compared to mice implanted
with tumors that need testosterone.
The researchers found that adding even low levels of testosterone
could shrink established tumors of hormone-independent cells.
Removing the added testosterone, or adding testosterone-lowering
drugs, caused the tumors to regrow.
The researchers dedicated the report to Huggins, who turned 95
last month and has been in ill health. The work was funded by
the National Institutes of Health.
Authors of the report in addition to Liao and Kokontis are visiting
professor Yoshihisa Umekita and senior research associate Richard