PCa pathway research could lead to new therapeutic targets

Late-stage advanced prostate cancer tumors appear to be driven by a different hormonal pathway than was previously thought, and now, researchers at the University of Texas Southwestern Medical Center, Dallas, have narrowed potential drug targets.

"Our findings will change the framework for the way people think about this disease," said senior author Nima Sharifi, MD.

"The general assumption is that the tumor accelerates through testosterone when, in fact, the pathway goes around it to the most potent hormone. We found the existence of this pathway in models and patients, and have shown that these resistant tumors are clearly driven by this other pathway."

In the current study, which was published online in the Proceedings of the National Academy of Sciences (July 27, 2011), UT Southwestern scientists analyzed prostate cancer cell lines, mouse models, and fresh tumor tissue from patients. Their findings suggest that potential drug therapies need to target an enzyme responsible for initiating hormone production earlier in the process.

"This now suggests that a potential drug target is one step upstream in the pathway," Dr. Sharifi said. "This can be thought of as charting a map of the correct pathway. You have to figure out which way the river flows before you can block the river."

The findings also will help researchers develop accurate biomarkers of response and resistance to hormonal therapies, which eventually will help identify why and how prostate cancer tumors become resistant, he said.