Although there are now many new treatments for advanced prostate cancer, hormone therapy (ADT) has remained the standard of care for the last 70 years. While hormone therapy can provide pain relief, it is never curative.
Long-term hormone therapy produces decreased quality of life. Men treated with hormone therapy have weight gain, experience impotence, decreased libido, muscle weakness, depression, anemia, thinning of the bone and memory loss.

Studies over the last decade have confirmed that prostate cancer cells maintain a life-long addiction to testosterone and other male hormones called androgens. In the cell androgens bind to a protein called the androgen receptor and prostate cancer cells rely on this receptor for growth and survival.

With hormone therapy, prostate cancer cells are forced to live in a low androgen environment. Those cells that don’t die in this low androgen environment but do adapt by increasing the amount of their androgen receptor. Even in men dying from progressive prostate cancer that is resistant to hormonal therapies (castrate resistant prostate cancer) this receptor continues to be present at very high levels where it protects prostate cancer cells from death.

Up until now, the main approach to treating prostate cancer once it has become castrate resistant is to add even more hormone treatments. These additional hormone treatments can produce transient benefit in some men, but in a relatively short time, the prostate cancer cells once again adapt and keep growing. Even at this stage, however, the prostate cancer cells still depend on the androgen receptor to stay alive. Therefore, a new strategy is needed to attacking this receptor in order to benefit men with castrate resistant prostate cancer.

A great surprise is that in laboratory studies castrate resistant prostate cancer cells that make high amounts of the androgen receptor are killed when exposed to high levels of testosterone. This result is exactly opposite of what is expected. We think what is happening is that prostate cancer cells must first make and then remove the androgen receptor in order to produce more cancer cells. In the presence of high levels of testosterone, the androgen receptor does not get removed from the cell like it is supposed to and this cause the cells to die when they try to divide to make daughter cells.

These laboratory results led the researchers to test this concept in a small clinical study in men with hormone-resistant prostate cancer. In this study they found that more than 50% of the men showed signs of prostate cancer response when treated with high doses of testosterone. In addition, all of the men reported remarkable improvement in quality of life. Many of the men were able to once again engage in sexual activity with their spouses. Muscle strength and energy level also markedly improved. Some men remained on treatment for a year or more.

These results suggest a new paradigm for treating prostate cancer that would involve sequentially lowering and then raising testosterone to high levels. This treatment is unique as far as cancer therapies go in that it has the potential to stop the growth of cancer while at the same time making the patients feel better, not worse.

As one might expect, the concept of using testosterone to treat prostate cancer is quite “out-of-the-box” and counterintuitive. Thus, it has been difficult to obtain funds from traditional grants sources to support these trials. Therefore, we are seeking funding from new avenues such as Start a Cure to test this concept further in men with advanced prostate cancer. Our goal is to generate enough patient data to garner support for larger trials with the hope that this cyclical testosterone therapy may gain acceptance as standard therapy for men with hormone-resistant prostate cancer.

This research project is being proposed by Samuel Denmeade, MD,
Avery Spitz, Michael Carducci, Emmanuel Antonarakis, Mario Eisenberger, and Harry Cao from the Johns Hopkins University

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Joel T Nowak, M.A., M.S.W.