How to Beat Castration-Resistant Prostate Cancer

Prostate cancer feeds on androgens – male hormones, like testosterone. A common tactic in the battle against prostate cancer is to deprive the cancer of the androgens it craves via androgen deprivation therapy. It won't kill the cancer, but it can slow it down, and against prostate cancer which usually moves glacially anyway, slowing it even more is often enough to checkmate it.

But androgen-deprivation therapy has always existed within a bit of a Catch-22 scenario. It works because the process creates oxidative stress within the cancer cells. But that same stress triggers a reactivated signaling by the androgen receptor in those cells, inhibiting the anti-hormone therapy.

How can we keep those “castration-resistant” cells from proliferating in the face of oxidative stress? The answer may already exist inside us.

Endostatin is a naturally occurring protein in humans. Researchers at the University of Alabama Birmingham believe they have isolated the androgen receptor – in this case the glucocorticoid receptor – causing the stress. When endostatin protein interacts with the glucocorticoid receptor, it pulls the plug on oxidative stress and reduces what oncologists call the “pro-tumorigenic function.” That is, it makes the cancer cells less cancerous. In the case of prostate cancer tumors, the introduction of endostatin prevents or delays the onset of castration-resistant disease.

In their preliminary tests on xenograft animals, treatment with endostatin resulted in a significant up-regulation of the major cellular machinery to scavenge destructive reactive-oxygen-species. Increased levels of reduced glutathione were accompanied by increased glucose uptake as the endostatin-treated cancer cells appeared to shift their metabolism to a different that utilized glucose to maintain the antioxidant system.

“Our study suggests that the potential therapeutic application of endostatin may include combination with the frontline androgen-deprivation therapy that targets prostate cancer at early stages,” the researchers wrote. “Based on the known anti-angiogenic properties of endostatin and on more interesting evidence that human prostate endothelial cells also express androgen receptor, the application of endostatin in combination therapies could synergize tumoristatic and tumoricidal effects with minimal resistance.”

The study has been published in The FASEB Journal.