LAKE TAHOE, Nev. -- As the average age of Americans rises,
preventing prostate cancer is becoming a vital area of research, and the focus
is turning from general recommendations about diet, such as eating less fat and
more fruits and vegetables, to exploring specific agents, including vitamins and
drugs.
About 30 percent of men between ages 30 and 39 have at least some
cancer cells in their prostate, and that number rises to 50 percent for men in
their fifties, said William G. Nelson, M.D., a medical oncologist at Johns
Hopkins University Hospital in Baltimore.
"It's a staggering thought,
even as the population gets older on average," he added.
To prevent
these indolent cancers from turning aggressive, scientists are exploring the
effects of a variety of substances, ranging from chemotherapeutic drugs used for
other cancers to substances found in foods. At the Advances in Human Breast and
Prostate Cancer conference here recently, researchers discussed this burgeoning
area of research called chemoprevention.
One of the more promising
possible chemopreventive agents comes from a class of drugs called selective
estrogen receptor modulators (SERMs). These are thought to act by plugging into
certain proteins on the surface of cells, thereby preventing estrogen from
binding to those same sites and promoting cell growth.
Blake Lee
Neubauer, Ph.D., is one researcher looking at a specific SERM with the
minimalist name LY353381-HCI to explore its potential for preventing the growth
and spread of prostate cancer. It's already being tested in phase II randomized
trials for women with breast cancer, and considering the hormone-based growth of
prostate cancer, it's being investigated for use in men with that disease as
well.
"[SERMs] may be useful in chemotherapy and prevention of both
breast and prostate cancers," he said.
For prostate cancer, Neubauer, a
senior research scientist at Eli Lilly Research Laboratories in Indianapolis,
discussed experiments involving LY353381-HCI and a line of hormone-sensitive
prostate cancer cells called LNCaP. His team is using the SERM to target an
estrogen receptor in the cell line called ER beta, with the goal of inhibiting
hormone-induced cell proliferation. Six days after exposure, they found the SERM
did just that.
The next step was to study the effects of the SERM on
LNCaP cells implanted in mice. The drug was found to have a marked anti-tumor
effect, and was well tolerated by the mice. "It also extends the time to
treatment failure [in the animals]," he said.
The question the team is
now exploring is whether the drug was mimicking chemical castration, a commonly
used therapy against hormone-sensitive prostate cancers that blocks the body's
production of hormones.
"SERMs are worthy of testing," Neubauer said.
"They have the kind of activity that may be relevant in prostate cancer
therapy."
And Don't Forget Antioxidants
Also of potential
relevance to the prevention of prostate cancer is a collection of agents ranging
from a substance found in tomatoes, to vitamins.
Among the major
cancers, prostate cancer is the least understood from an epidemiological point
of view, observed Ronald Ross, M.D., an epidemiologist from the University of
Southern California in Los Angeles, "which makes it difficult to target
prevention pathways."
Some substances that merit future research in
Ross's view are antioxidants, androgen suppressors and vitamin D. "Each of the
pathways [these substances affect] has several biological goals in common," he
said, which are decreasing cellular proliferation, increasing cellular
differentiation (return to a normal mature form), increasing apoptosis
(programmed cell death) and decreasing mutations.
Based on a 1993 study
out of the California-based Kaiser-Permanente group, there's evidence supporting
vitamin D as a chemopreventive agent, Ross said. But scientists are still
working out how to prevent hypercalcemia, a common side effect of taking too
much of the vitamin.
The antioxidants include selenium, lycopenes and
vitamin E. Antioxidants neutralize free radicals, which can cause potentially
cancer-stimulating DNA mutations.
A Harvard study found that men with
higher selenium levels had a reduced risk for prostate cancer, and a study out
of the University of Arizona reported that men who took 200 micrograms of
selenium had 63 percent fewer prostate cancers than a control group. Both
studies are preliminary and need confirmation.
Lycopenes, found mainly
in tomatoes, have been receiving more and more attention, he added. "Overall I
find the evidence fairly convincing," Ross said. "Lycopenes warrant further
study as a chemopreventive agent."
There's very little direct evidence
that vitamin E protects against prostate cancer, he said, but there is some
secondary evidence of efficacy. Ross cited a study of lung cancer in Finnish men
who smoked and were given vitamin E. The men were tracked for six years, and it
turned out those who received the supplements had a significant reduction in
prostate cancer incidence and mortality. "It obviously looks like an agent that
deserves further study," he noted.
