FOR IMMEDIATE RELEASE
Mary Jane Gore
434-924-9241
mjgore@virginia.edu
 
UVa Researchers Win Competitive Award to Aid Men with Advanced Prostate Cancer
 
The Bottom Line: UVa researchers work on “smart bomb” treatment for men with advanced prostate cancer and a test for several proteins produced by cancerous cells to learn how prostate cancer could be treated or prevented. Prostate cancer will strike 1 in 2 men.
 
CHARLOTTESVILLE, Va., April 20, 2006--Two teams of researchers at the University of Virginia Health System have received funding for high-impact laboratory research projects that have great potential to improve treatment for men with advanced prostate cancer. The funding is part of the 2005 Competitive Award from the Prostate Cancer Foundation.
 
Michael Weber, Ph.D., professor of microbiology and director of the UVa Cancer Center, and John Chirgwin, Ph.D., professor in the UVa Division of Endocrinology and Metabolism, each received grants of $100,000 for their respective basic research projects. This preliminary work will lay the groundwork for future trials for tests and drugs that could be tested in people.
        
Activation of the MAP Kinase cell-signaling pathway has been shown in earlier work from the Weber lab to induce growth of hormone-resistant prostate cancer cells. Dr. Weber is studying whether inhibitors of this pathway can restore androgen dependence to prostate cancer cells in culture, and whether this drug combined with other drugs might be even more effective.           

"The new generation of anti-cancer drugs is based on knowing the molecular 'targets' that are driving the growth, metastasis and survival of the cancer. Such drugs are sometimes compared to 'smart bombs' that specifically hit these targets, slowing down or destroying the tumor while causing less collateral damage," Dr. Weber says. "It is becoming clear that for most cancers, it will take more than one kind of smart bomb to eliminate the cancer. We are working on ways to identify the optimal combinations of targeted therapies that can be used to treat advanced prostate cancer."

The target in this work is the MAP Kinase pathway, which was discovered at UVa by Tom Sturgill, professor of pharmacology and medicine. Inhibiting this pathway can be an important component of a multi-targeted approach to treatment, Weber says.

The development of bone metastases is a painful and often debilitating effect of progressive prostate cancer. In a different project, Dr. Chirgwin is studying the interactions among different proteins produced by prostate cancer cells in an attempt to determine whether bone metastases can be treated and/or prevented.

“Advanced prostate cancer often metastasizes to bone,” said Chirgwin, “where it causes painful, disorganized new bone formation."

Dr. Chirgwin and his colleague Theresa Guise, M.D., with whom he collaborates extensively, will incorporate a combination of biological targets into their developing test, including prostate-specific antigen – commonly known as PSA. By learning more about the presence and interactions of certain biological targets, the researchers ultimately will aid research into drugs that can help to treat or prevent advanced prostate cancer.

Their previous laboratory experiments solved a confusing problem: prostate cancers secrete a factor, called PTHrP, that causes the bone destruction characteristic of metastatic breast cancer, but bone metastases in prostate cancer are unlike those in prostate cancer patients. "We found that prostate specific antigen, PSA, converts PTHrP from a bone-destroying factor into fragments that are bone-stimulating," Chirgwin said. "Our new project is to develop an assay to determine how important this conversion is in patients. Drugs exist that block the PSA-produced fragments. The assay will identify candidates for specific drug treatment to reduce the complications of bone metastases in men with advanced prostate cancer.” 

The Competitive Awards Program of the Prostate Cancer Foundation is an innovative venture-style research funding program that provides financial support to high-impact research projects with the greatest potential to improve near-term treatments for men with advanced prostate cancer. The awards are granted to projects in a variety of areas including genomics, proteomics, clinical development, signal transduction and nutrition.
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