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Key to Prostate Cancer Resistance

Findings suggest combination of therapies that may help treat resistant prostate cancers

October 31, 2014 | Dikshya Bastakoty

prostate cancer cells

Prostate cancer cells. (Wellcome Images)

Androgen-deprivation therapy in most prostate cancer patients results in an initial regression of tumor. This is followed invariably by what is known as “castration resistance.”

Normally, the male hormone androgen binds to the androgen receptor in the prostate, signaling the tumor to grow. But in the castration-resistant tumor, the androgen receptor is overexpressed or mutated, causing the system to be active even when it is deprived of androgen. What drives this androgen receptor variant expression is poorly understood.

In a paper published in Oncogene, Renjie Jin, M.D., Ph.D., and colleagues reported that activation of nuclear factor kappaB (NFkappaB) signaling in prostate tumor cells grown in culture or in animals causes castration resistance by increasing the expression of both the regular and the mutated variants of the androgen receptor.

A combination of traditional anti-androgen therapy with NFkappaB-targeted therapy decreased expression of receptor variants and reversed castration resistance, suggesting that may be effective in treating castration-resistant prostate cancer in humans.

The study was supported in part by the Department of Defense Prostate Cancer Research Program and by the National Cancer Institute (CA076142).