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Molecular targeting: Prostate SPORE zooms in on RTVP-1 gene
By John Tyler

Timothy C. Thompson, PhD

Timothy C. Thompson, PhD, and his team of researchers at Baylor College of Medicine are now examining the potential of a newly discovered gene to kill prostate cancer cells and create a long-lasting resistance to related cancer outside the gland.

"This is exactly what we were looking for in a gene," said Thompson, a Baylor professor of urology, radiology and molecular and cellular cell biology and director of the Specialized Program in Research Excellence (SPORE) for prostate cancer at Baylor. "It is very unusual for a gene to create this type of therapeutic response and joins a very short list that has this kind of impact."

The SPORE in Prostate Cancer, where the work is being done, was recently renewed for a five-year period by the National Cancer Institute, which awarded the program $14 million to carry out its work.

The Baylor Prostate SPORE focuses on promoting novel and creative research as well as translating basic research findings from the laboratory to actual patient treatment. The program hopes to reduce cancer incidence and deaths and improve survival for those with the disease. A primary focus for the research is molecular targeting, which could one day lead to the development of drugs that block the spread of the disease.

Prostate cancer is the most common form of cancer in American men and the second most common cause of cancer death in that population. (Lung cancer is the first.) More than 180,000 men in the United States will be diagnosed with prostate cancer this year, and more than 40,000 will die of the disease. At least 75 percent of all prostate cancers are diagnosed in men over age 65. When the cancer is confined to the prostate, survival is excellent after surgical removal of the prostate. The prognosis is much poorer for prostate cancer that has spread.

Within the next year, Thompson and the Baylor research team will start recruiting patients for a clinical study to test the gene RTVP-1 that they hope will prove a prostate cancer killer. When injected into animals with prostate cancer, the gene has been found to kill tumors and promote a resistance to future cancers.

"Right now, there really is no effective treatment for prostate cancer once it moves outside the prostate," Thompson said. "This gene seems to create a signal within the immune system that tells the body it needs to respond to the situation."

Thompson pointed out that this is similar to the way the body's immune system acts in response to infections. "We are, in essence, making the cancer appear as a germ to the body's immune system," he said.

Additionally, the Baylor researchers have found that the potency of this treatment is intensified when used in tandem with radiation therapy. Thompson said he believes ultimately supplementing radiation therapy with this new gene will greatly enhance men's chances of survival.

Another goal Thompson has set for himself and his researchers is to develop a new test to complement the prostate specific androgen (PSA) exam for men. The test detects rising blood levels of a particular protein that is associated with the development and progression of prostate cancer.

"When added to the current PSA exam men over 50 should get each year, this test will tell more specifically whether cancer cells have the potential of spreading outside the prostate," said Thompson.

The new test will check for the level of caveolin-1, a protein linked with more aggressive forms of the disease.

"We already know that caveolin-1 is associated with and specifically secreted by aggressive prostate cancer cells," he said. "We hope to rapidly develop caveolin-1 as a diagnostic/prognostic biomarker and eventually as a therapeutic target."

An annual PSA exam is still vital for catching this deadly disease early. "However, the current PSA test is not a direct marker for prostate cancer, " he said. "It does not differentiate between normal prostate cells and prostate cancer and it does not tell us whether the cancer will turn out to be more deadly."

Over the past several years, Thompson and his team of researchers have identified the genes that are involved in the spread of prostate cancer. Now, they plan to use this knowledge to assess the potential of cancer to spread and to develop new therapies.

"Mortality could be reduced if we had better clinical tools to assess the potential of the disease, and if we could more rapidly advance new experimental therapies," Thompson said. "Our goal is to develop the means to accurately predict the course of the disease and to develop new therapies so that the cancer can be treated successfully regardless of what stage it has reached."

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