Failure of hormone deprivation therapy, which is used to slow prostate cancer in patients, leads to castration-resistant prostate cancer, a lethal form of advanced disease with limited treatment options. University of Alabama at Birmingham (UAB) researchers have discovered that endostatin, a naturally occurring protein in humans, can significantly decrease proliferation of castration-resistant prostate cells in culture, and in a paper published online on January 9, 2017 in The FASEB Journal, they describe the physiological pathways and signaling evoked by endostatin. The article is titled “Endostatin Inhibits Androgen-Independent Prostate Cancer Growth by Suppressing Nuclear Receptor-Mediated Oxidative Stress." This endostatin effect is now being tested in a preclinical xenograft animal model of castration-resistant prostate cancer. "We hope we can delay the onset of castration-resistant disease," said Selvarangan Ponnazhagen, Ph.D., a UAB professor in the UAB Department of Pathology who holds an Endowed Professorship in Experimental Cancer Therapeutics at UAB. The medical treatment that deprives prostate cancer cells of androgen hormones through anti-hormone therapy creates oxidative stress in those cancer cells. This oxidative stress is associated with reactivated signaling by the androgen receptor in the cells, causing resistance to the anti-hormone therapy. The UAB researchers, led by Dr. Ponnazhagen and first author Joo Hyoung Lee, Ph.D., hypothesized that the oxidative stress might be triggered upstream of the androgen receptor, with the glucocorticoid receptor as the stress-inducer. If so, endostatin might interact with the glucocorticoid receptor to remove the oxidative stress and reduce that pro-tumorigenic function in the cancer cells, thereby preventing or delaying the onset of castration-resistant disease.
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