| Right now, there are two keys to detecting prostate
cancer early: The digital rectal examination, and the blood test for prostate-specific
antigen, or PSA. The use of both of these, plus safer surgical treatment
of early-stage disease, has led to five-year survival rates for localized
prostate cancer now approaching 100 percent, says Christian Pavlovich,
M.D., associate professor of urology, and Director of Urologic Oncology
at the Johns Hopkins Bayview Medical Center. But early detection is still
far from perfect, he adds. “There are still many men who undergo
biopsy needlessly, and others in whom these tests fail to detect early
disease.We still miss quite a few cancers.”
The challenge, then, is to come up with better tests. One approach is
to look for ways to get more out of PSA. Heading this school of thought
are pioneering scientists such as Alan Partin, M.D., David Hall McConnell
Professor and Director of Urology, and colleagues at the Brady, who are
exploring different forms of PSA — such as “percent free PSA,”
and “complexed PSA” —in hopes of developing more specific
tests.
Another approach is to look for a different biomarker, or substance made
by the cancer that can be measured. With this in mind, Pavlovich and colleagues
have zeroed in on a highly promising candidate — a protein that’s
been found in prostate cancer, and inthe urine of men with prostate cancer.
This molecule, called AMACR (for alpha methylacyl CoA racemase; rhymes
with “eraser”) is involved in fatty acid metabolism, and it
was first linked to prostate cancer by Jun Luo, Ph.D., Angelo M. DeMarzo,
M.D., William Isaacs, Ph.D., and colleagues at the Brady Urological Institute.
Although it’s not yet clear exactly what the connection is between
fatty acids and prostate cancer, Pavlovich’s group has found that
urinary AMACR is tightly linked to prostate cancer. In a small study,
they found that the presence or absence of urinary AMACR accurately predicted
whether a man had prostate cancer 86 percent of the time.“Most exciting
for us is that AMACR was found in the urine of all of the men who had
prostate cancer,” says Pavlovich. “The sensitivity was one
hundred percent.”
With funding from the National Institutes of Health, Pavlovich is attempting
to develop a quantitative assay for urinary AMACR that will make testing
easier and even more reliable. He is also searching fo rother urinary
biomarkers for prostate cancer, “with the hope that noninvasive
urinary testing for prostate cancer can soon become a reality for all
men.”
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