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Peek Into Future of Prostate Cancer

Prostate Cancer Vaccine, Better Tests May Be Just Over the Horizon

Reviewed by Louise Chang, MD on February 01, 2008
From the WebMD Archives

Feb. 1, 2008 -- A better prostate cancer test -- and a vaccine to keep early prostate tumors at bay -- may be just over the horizon, new studies suggest.

The current PSA screening test for prostate cancer isn't as sensitive or specific as anyone would like. The test sends many men to doctors for needless biopsies. It fails to identify many men who have dangerous cancers. And even when it detects cancer, it can't tell whether the cancer is aggressive.

Experimental cancer vaccines haven't worked well at all. They've been explored as last-ditch treatments when standard treatments fail, and they've been used to mop up cancer cells left behind after surgery. Results of such studies have been disappointing.

Now researchers at the University of Michigan report incremental progress in an improved urine test for prostate cancer. And exciting mouse studies at the University of Southern California suggest that when tests identify men with early prostate cancer, vaccination can keep the cancer from ever becoming deadly.

Both studies appear in the Feb. 1 issue of the journal Cancer Research.

Don't Watch and Wait -- Vaccinate

"This represents a paradigm shift in how we treat prostate cancer," W. Martin Kast, PhD, USC professor of microbiology and immunology, tells WebMD.

Kast hasn't treated any humans. But his team has done something nobody else has ever done. Their new vaccine keeps a strain of mice alive indefinitely, even though they are genetically programmed to die of prostate cancer.

The state-of-the-art vaccine is a two-step process in which mice are inoculated against a protein that becomes more and more abundant in prostate cancers as they morph fromprecancerous "prostate intraepithelial neoplasia" (PIN) into aggressive cancers.

So-called TRAMP mice develop prostate cancer as soon as they reach puberty. Kast and colleagues vaccinated the animals just as they developed the early PIN. While all unvaccinated mice died, 18 of 20 vaccinated mice lived to be 1 year old -- the oldest TRAMP mice ever seen.

A close look at the surviving animal's tumors showed that they did not go away. The animal's genetic programming kept trying to turn the early cancers into deadly tumors. But immune cells swarmed around the cancers, keeping them at bay.

Continued

"The equivalent in a man is very clear. In the U.S., for instance, some 90,000 to 100,000 men every year are diagnosed with high-grade PIN," Kast says. "That is the exact equivalent of the disease stage in mice. So there is a group of men that could benefit very much from this approach."

A big worry is that the vaccine's target is a protein found on normal cells in the esophagus, bladder, and stomach. But at least in mice, the vaccine did not harm these organs.

"I think the explanation is that the expression levels of this protein, PSCA, is so low in normal tissue that the immune system makes a differentiation between prostate cancer cells that make this antigen and normal cells," Kast says.

Kast says his team could produce a human vaccine in about two years. Any actual vaccine treatment would need years of testing before it became available, notes Durado Brooks, MD, MPH, director of prostate and colorectal cancers for the American Cancer Society, Atlanta.

"I would hesitate to get too excited about this vaccine study, since we are at this point we are talking about mice -- and the jump from mice to men is usually many years in the making," Brooks tells WebMD. "It certainly does open the door to some potentially exciting avenues, but we are not right around the corner from being able to duplicate these results in human populations."

Better Prostate Cancer Test?

A major problem with the PSA prostate cancer screening test is that it looks for only one prostate-specific protein, notes Arul M. Chinnaiyan, MD, PhD, professor of pathology and urology at the University of Michigan.

Chinnaiyan's team is therefore looking at what they call a "multiplex" test that will look for a number of prostate cancer markers. In their current study, they have looked at four such markers in the urine of 234 men whose high PSA levels caused them to have prostate biopsies.

The new test wasn't perfect. But it identified 80% of the men who turned out to have prostate cancer. And it was able to rule out prostate cancer in 61% of the men whose biopsies were negative.

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"Before biopsy, this test is identifying prostate cancer better than the PSA test," Chinnaiyan tells WebMD. "The idea is that a patient would come in with an elevated PSA score, and we would be able to give him this second test. Ideally, it would be a multiplex test with a variety of prostate cancer markers. We are going to go away from single markers to multiple markers in the near future."

Continued

The American Cancer Society's Brooks notes that the new test doesn't address the biggest problem for prostate cancer screening.

"Just finding more cancers is not necessarily a good thing," Brooks says. "All prostate cancers are not created equal. What we need is a better tool to identify those cancers that are more likely to be aggressive and result in a benefit if identified patients are treated."

Chinnaiyan admits that the new test, in its current form, cannot do this. But he notes that one of the markers used in the test is a "gene fusion" marker of more aggressive cancers. By finding and using more such markers, he says, the test may one day predict the aggressiveness of a man's prostate cancer.

"But we want to take baby steps and tackle the diagnostic aspects of the test first," Chinnaiyan says.

WebMD Health News

Sources

SOURCES:

Garcia-Hernandez, M. Cancer Research, Feb. 1, 2008; vol 68: pp 861-869.

Laxman, B. Cancer Research, Feb. 1, 2008; vol 68: pp 645-649.

W. Martin Kast, PhD, professor of molecular microbiology and immunology, University of Southern California, Los Angeles.

Arul Chinnaiyan, MD, PhD, professor of pathology and urology, University of Michigan, Ann Arbor.

Durado Brooks, MD, MPH, director, prostate and colorectal cancers, American Cancer Society, Atlanta.

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