Key Piece to Prostate Cancer Puzzle Found

An unexpected discovery has turned up a key piece to the
prostate cancer puzzle.

The finding comes from a powerful new science called metabolomics. Using
these new techniques, scientists discovered that urine levels of an obscure
amino acid derivative called sarcosine show whether a man has aggressive or
benign prostate cancer .

To the scientists' surprise, sarcosine wasn't just a harmless marker.

Benign prostate cancer cells exposed to sarcosine suddenly turn nasty,
becoming aggressive and invasive cancer cells. Aggressive prostate cancer cells
that can't get sarcosine are tamed, becoming much less invasive.

If confirmed and validated in larger studies, the findings have huge
implications for prostate cancer treatment , says study leader Arul M.
Chinnaiyan, MD, PhD. Chinnaiyan is professor of pathology and urology at
University of Michigan, Ann Arbor.

"We have tantalizing evidence that this sarcosine pathway may be
involved in the pathogenesis of prostate cancer," Chinnaiyan said at a news
conference. "Therapeutically, we could envision small molecules or
antibodies that might inhibit some of the pathway components that lead to
sarcosine upregulation."

If the finding leads to new tests, it would have a huge impact on how
prostate cancer is treated, University of Michigan urologist John T. Wei said
at the news conference.

"One big clinical issue in prostate cancer is trying to distinguish
aggressive prostate cancer from the indolent version of the disease," he
said. "What we doctors end up doing is over-treating patients because we
can't distinguish aggressive from indolent disease."

The findings validate metabolomics and a brand new technology using
computer-driven robotic machines that can rapidly identify all the various
chemicals that build up inside the cells of the body.

This chemical buildup consists of metabolites -- the end products of the
vast number of biochemical reactions that take place within cells.

By comparing the metabolites from normal cells to those of indolent and
aggressive prostate cancer cells, Chinnaiyan and colleagues detected at least
10 metabolites that distinguish normal cells from cancer cells -- and which
increase or decrease in frequency as cancer cells get more aggressive.

Once identified, a simple urine test can detect the metabolites. And if
detecting sarcosine gives a lot of information, detecting additional
cancer-specific metabolites will make an eventual test exponentially more
useful.

"Moving forward, we would develop a panel of these metabolites we could
monitor in urine or in tissues," he says. "The idea would be to develop
several of these metabolites we could measure simultaneously."

That's still a long way off. Right now, just looking for sarcosine in urine
would not give much information. Large numbers of men, at various stages of
prostate cancer, will have to be enrolled in validation studies.

Might these future tests make dreaded needle biopsies of the prostate
obsolete?

"Right now, we don't have enough confidence in these new biomarkers to
do that, but that may be possible in the future," Wei says.

Chinnaiyan and colleagues report the findings in the Feb. 12 issue of the
journal Nature.

By Daniel DeNoon
Reviewed by Louise Chang
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