Timing is Everything:
DeWeese, left, and Hales found that treating prostate cancer cells with hormonal therapy,
then testosterone and radiation, worked better.
For men with high-risk prostate cancer, the combination of short-term hormonal therapy and radiation is the standard of care. “This has resulted in better control of cancer in the pelvis, reduced the risk of metastatic disease, and increased survival,” says Theodore L. DeWeese, M.D., Ph.D., Chairman of the Department of Radiation Oncology and Molecular Radiation Science. “However, despite this great advance, cancer still recurs in a number of patients with this aggressive type of prostate cancer.”
DeWeese and colleague Russell Hales, M.D., have been thinking about this problem for some time. Recently, they reviewed an experiment done years ago by Don Coffey, Ph.D., The Catherine Iola and J. Smith Michael Distinguished Professor of Urology and the Brady’s former Director of Research, who spent his career studying how cells — normal and cancerous — are structured, and how they behave. One thing Coffey learned was that just like the tide, which changes depending on the phase of the moon, cancer cells vary, too. Depending on where they are in their cycle of making new DNA and dividing in two, they are more or less vulnerable to radiation. “We also knew that hormone therapy kills prostate cancer cells that are hormone-responsive while also putting the other, surviving cells into a non-cycling state, a state in which the cells are thought to be more resistant to radiation,” says DeWeese.
Taken together, these two facts led DeWeese and Hales to believe that maybe timing could make a difference in cancer-killing power. “We performed a series of experiments,” DeWeese says, and in mice found that “when prostate cancer tumors are treated with hormonal therapy, followed by testosterone and radiation, they are more likely to be controlled” than cancers in mice that received hormonal therapy and then radiation without testosterone. “This is very exciting news.”
Next, the team plans to work with Brady scientist Vasan Yegnasubramanian to understand some of the basic science behind this testosterone-radiation interaction, and then to develop novel clinical trials based on this three-part combination.