Could more testosterone be the hidden key to fighting prostate cancer?

Categories: Summer/Fall 2022
Egret
Focused efforts in the application of new ideas can lead to innovation in the fight against prostate cancer.                                                                                  ©  Ron Woolridge

Researchers at Johns Hopkins are finding that using high-dose testosterone makes cancer more
receptive to other treatments.
Androgen deprivation therapy (ADT) slows progression of prostate cancer by shutting off
testosterone. Eventually cancer adapts to this environment and PSA levels start to rise; this is
called castrate-resistant prostate cancer (CRPC). Long term ADT causes fatigue, hot flashes,
weight gain, and loss of sexual function.

Samuel Denmeade, MD, Co-Director of the Johns Hopkins Prostate Cancer Program devised the
concept of attacking prostate cancer by alternating ADT with high-dose testosterone
©administration. When low doses of testosterone are given to cancer cells, they grow, but when
given high doses the cancer cells don’t grow as well, or they die.

About ten years ago, Denmeade conducted a small study to test the concept of using
testosterone to fight prostate cancer. His hypothesis: prostate cancer cells adjust to a very low-
testosterone environment (created by ADT) by making very high levels of the androgen
receptors. These high levels of the androgen receptor now make cancer vulnerable to very high
levels of testosterone. Cancer cells that survive this respond to high dose testosterone by
scaling the androgen receptor back down which makes the cancer again susceptible to very low
testosterone levels. The idea is to interrupt the cancer cell’s ability to adapt by cycling between
high and low testosterone levels. Denmeade and colleagues named the approach bipolar
androgen therapy (BAT), to capture the polar extremes of very high and very low testosterone
levels. This early study included just a small number of patients. The initial clinical data showed that BAT was safe. Larger studies at Johns Hopkins have followed as well as other trials at the
University of Washington, University of Colorado, Australia, Brazil, and the Netherlands.

A Trial of BAT has recently opened in the Veterans Administration system for men with certain
types of metastatic castrate-resistant prostate cancer. We must wait for these validation trials
to conclude before assessing the significance of this initial Hopkins study.
Prostate Cancer Foundation. 2022 Jan 8

Subscribe to Quest