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Is it cancer, or another prostate problem?
One of his first targets is PSA. A major drawback to using PSA (prostate-specific
antigen) to detect cancer is that it doesn’t show only cancer, Getzenberg
says. “PSA is a normal product of the prostate that is found at
high levels even within the normal prostate.” Men who have a PSA
of between 4 and 10 ng/mlhave roughly a 25 percent chance of having prostate
cancer, he continues, “which means that more than 75 percent of
the men biopsied do not have the disease.”
So Getzenberg has been wondering: What
does prostate cancer make, that normal prostate tissue doesn’t?
And he’s found what may be a good answer: “We have developed
a novel biomarker for prostate cancer called early prostate cancer antigen
(EPCA),” he says.“One interesting characteristic is that this
marker is elevated not only in the prostate cancer itself, but in the
entire prostate of men with the disease.” However, he adds, men
who don’thave prostate cancer — even men with other prostate
problems, such as BPH and prostatitis— don’t show any EPCA
within their prostate.
EPCA, which is already available as
a test for pathologists to use, could be particularly useful in evaluating
negative prostate biopsies: If a stain of prostate cells shows elevated
EPCA levels, this would indicate that prostate cancer exists — even
if the needle samples didn’t find it. “But the absence of
EPCA staining would reveal that there is no prostate cancer within the
gland,” Getzenberg continues, and the patient can relax, knowing
he doesn’t need to have another biopsy right away.
| “Which men
have prostate cancer with the potential to kill them, and which men
have prostate cancer that is more like a pussycat?” |
Getzenberg and colleagues have also
developed an EPCA blood test, to go along with the PSA test, that can
help doctors figure out what’s causing the PSA to rise — namely,
whether it’s cancer, or another prostate problem. The EPCA blood
test is “highly specific for prostate cancer,” he says. “Men
with elevated EPCA levels have about a 90- to 95-percent chance of having
prostate cancer.” Clinical trials for this EPCA blood test have
already been conducted, and a larger study is now under way.
Is the
cancer slow-growing, or aggressive? “Which
men have prostate cancer with the potential to kill them, and which men
have prostate cancer that is more like a pussycat?”Getzenberg has
developed a test to help determine this, using a new, blood-based prostate
cancer marker (one of several he’s testing) called EPCA-2. “We
have evidence that EPCA-2 appears to be elevated at its highest levels
in men with most aggressive forms of the disease.” However, EPCA-2
shows up at much lower levels in men with less aggressive cancer. EPCA-2
is now being tested inclinical trials.
BPH, like
cancer, can be “good” or “bad.”
Benign enlargement of the prostate (BPH), doesn’t just affect the
prostate, and it isn’t always benign. It affects the bladder, and
in severe form, its symptoms can be debilitating. “Until recently,
all BPH was considered to be a single disease,” notes Getzenberg.
But his research group has found a genetic marker, called JM-27, that’s
associated with the most aggressive type of BPH. Further, Getzenberg and
colleagues have developed a blood test that can determine whether a man
has the most severe form of BPH, or whether his case is mild. They hope
that this test will even be able to predict how a man will respond to
various treatments of BPH. “This is the first BPH-specific marker
that has been identified, and we hope it will play a role in how men are
treated for the disease,” he says.
Markers
for bladder cancer: Getzenberg’s search for
markers has extended to bladder cancer. “Bladder cancer is the second
leading urologic cancer, and it has increased significantly over the past
couple of years,” he explains. He and colleagues have identified
several novel markers for bladder cancer, and have developed a simple
urine test for one of these, called BLCA-4. BLCA-4 may have other uses,
as well: It appears to regulate gene expression within the bladder, and
also to affect certain proteins that may be important in the development
of the disease. Getzenberg and colleagues have developed a similar urine
test for another marker, called BLCA-1, and hope to combine these two
as says in clinical studies. These markers are being tested in a large
clinical trial of more than 3,000 patients.
BPH and
cancer — any connection? BPH and prostate cancer
affect different regions of the prostate, but they’re both associated
with aging. They may have other things in common, as well, says Getzenberg.
“We have identified a series of genes that appear to be altered
in both BPH and prostate cancer. There may be much more connection between
BPH and prostate cancer than we originally envisioned. Understanding more
about the development of each of these diseases will help us develop better
tools with which to attack them both.”
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