Discovery
January 22, 2016

Hormonal therapy takes away a driving force of prostate cancer – testosterone. It can work well for many years, but eventually the prostate cancer cells figure out how to adapt to the low-testosterone environment, and they begin to grow. But studies in the lab of Brady scientists John Isaacs, Ph.D., and Samuel Denmeade, M.D., have shown that these "testosterone-deprived prostate cancer cells can be paradoxically killed" by treatment with something they didn't expect — high amounts of testosterone, says Denmeade.

Based on this observation, Denmeade and colleagues recently carried out a pilot clinical trial that showed that a monthly injection of high-dose testosterone could be safely given to men with castrate-resistant prostate cancer, and that it produced a therapeutic benefit in some men. These exciting findings were published in the journal, Science Translational Medicine. In addition, Denmeade says, "we observed that after treatment with high-dose testosterone, in most cases the prostate cancer cells became re-sensitized and were no longer resistant to treatments that lower or block testosterone." In other words, the treatment had a double impact: After being bombarded with testosterone, prostate cancer cells were once again susceptible to hormonal therapy.

The treatment had a double impact: After being bombarded with testosterone, prostate cancer cells were once again susceptible to hormonal therapy.

These results were promising enough for Denmeade to received funding from both the National Institutes of Health and the Department of Defense's Prostate Cancer Research Program to perform more clinical studies at Johns Hopkins. He and colleagues will be testing this concept in larger groups of men with prostate cancer that has become resistant to standard hormone deprivation treatments. "Our goal with these clinical studies is to establish a role for high-dose testosterone as an inexpensive treatment that could improve quality of life, reduce disease burden and potentially reverse therapeutic resistance in men with advanced prostate cancer," he says. "We hope to establish this as an effective therapy that can improve survival, overcome resistance to hormonal therapy, and meaningfully improve quality of life, functional activity, and sexual function in men with castrate-resistant prostate cancer."

Denmeade was the principal investigator on the pilot study. Co-authors on the paper include Michael Schweizer, Emmanuel Antonarakis, Hao Wang, Seun Ajiboye, Avery Spitz, Haiyi Cao, Jun Luo, Michael Haffner, Srinivasan Yegnasubramanian, Michael Carducci, Mario Eisenberger, and John Isaacs.