New target may disrupt bladder cancer metastasis

Researchers from the University of Virginia Health System, Charlottesville, have found a potential new target and therapy for disrupting bladder cancer metastasis. Dan Theodorescu, MD, and colleagues identified endothelin-1, which directly correlated with lower levels of a beneficial factor called RhoGD12. Earlier, this same team found that when RhoGD12 was not present in high amounts in bladder cancer patients, the patients survived for shorter lengths of time.

Dr. Theodorescu found that the levels of endothelin were lowered when the activity of RhoGD12 was restored. Using a mouse model of metastatic bladder cancer, the team found that atrasentan, a drug in clinical trials, dramatically decreased lung metastases compared with untreated mice. If the same biology holds true in humans, similarly blocking the endothelin pathway with drug therapy may prevent lung metastasis and would provide a new treatment for bladder cancer patients.

"Discovering how to block the process of metastasis, we could wipe it out or at least keep the spread to a minimum." Dr. Theodorescu said. "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."