For immediate release
Contact: Mary Jane Gore
mjgore@virginia.edu
(434) 924-9241

UVA HEALTH SYSTEM PHYSICIANS FIND POTENTIAL TARGET THAT INTERRUPTS PROCESS OF BLADDER CANCER SPREAD

CHARLOTTESVILLE, Va., Oct. 7 –University of Virginia Health System researchers have found a potential new target and drug for disrupting the process of bladder cancer metastasis (cancer spread). In bladder cancer, the spread of cancer cells to the lungs is common and deadly. While searching for new ways to slow or reduce the process of metastasis, researchers found a gene that, when blocked, led to a dramatic reduction of lung metastasis. Likewise, they found that atrasentan, a drug in clinical trials for hypertension, can suppress certain genes and block metastasis. Their findings point to a potential framework for a clinical trial involving bladder cancer patients at high risk of developing lung metastasis.

“Evidence shows us that in some patients there is a window of time during which the cancer in the distant organ, in this case the lung, is at its most sensitive," says Dr. Dan Theodorescu, principal investigator. "Discovering how to block the process of metastasis, we could wipe it out or at least keep the spread to a minimum. Learning which genes to block and which to activate is part of the equation; we are also excited to find a compound that helps to block metastasis.”

Theodorescu, who is Paul Mellon Professor of Urology and Molecular Physiology at UVa Health System, and researchers identified a gene, endothelin-1 (ET-1), which directly correlated with lower levels of a beneficial factor called RhoGDI2. Earlier, the same UVa team found that when RhoGDI2 was not present in high amounts in bladder cancer patients, they survived for shorter lengths of time.

Because it is not practical to clinically restore RhoGDI2 activity in patients with bladder cancer, the team took a different approach, looking for genes that are suppressed by RhoGDI2. They learned that the levels of endothelin (a substance that causes blood vessel constriction) were lowered when the activity of RhoGDI2 was restored. Using a mouse model of metastatic bladder cancer (the same one used to discover RhoGDI2), researchers found that atrasentan – an agent that specifically inhibits ET-1 action – dramatically decreased lung metastases compared with untreated mice. If the same biology operates in humans, it could mean that similarly blocking the endothelin pathway with a drug may prevent lung metastases and would provide a new treatment of benefit to bladder cancer patients.  Dr. Theodorescu’s work on RhoGDI2 was published in a recent issue of the journal Cancer Research.

CONTACT: Dan Theodorescu, M.D., Ph.D., theodorescu@virginia.edu

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