Key to Hormone-Resistant Prostate Tumors Discovered

Key to Hormone-Resistant Prostate Tumors Discovered

Michael Karin, Ph.D.
University of California San Diego
R01ES006376

NIEHS-supported researchers at the University of California San Diego have found that prostate cancer treatments designed to suppress or block the production of male hormones trigger an inflammatory response that could be partly responsible for the development of resistance to these therapies within 12-18 months. These findings make a strong case for combining androgen ablation therapy with drugs already commercially available that block lymphotoxin signaling in B cells.

Androgen suppression can be achieved by surgical removal of the testicles, by taking female sex hormones, or by taking other androgen suppressors. Using a mouse model of prostate cancer, the researchers demonstrated that androgen deprivation killed tumor cells but caused them to release pro-inflammatory factors. This release led to the infiltration of the tumor by leukocytes. Further studies implicated B cells and the lymphotoxin they produced as promoters of castration-resistance prostate cancer.

Several strategies to deplete b cells all delayed the growth of castration-resistant prostate cancer in mice which is the most malignant and aggressive form of the disease. The current study used two mouse models, but the investigators have already confirmed their finding with human prostate cancer tissues. The research note that extrapolation of their findings to humans suggests that castration-resistant prostate cancer could be delayed by about three years when the B cell depletion therapy is incorporated with standard treatments.

Citation: Ammirante M, Luo JL, Grivennikov S, Nedospasov S, Karin M. B-cell-derived lymphotoxin promotes castration-resistant prostate cancer. Nature. 2010. Mar 11;464(7286):302-5.
Key to Hormone-Resistant Prostate Tumors Discovered