Androgen content and BET bromodomain proteins influence enzalutamide agonism of mutant F876L androgen receptor.

e16538 Background: One emergent resistance mechanism to medical castration is intratumoral androgen synthesis that activates the androgen receptor (AR). This insight led to the development of the AR antagonist enzalutamide. One enzalutamide resistance mechanism is AR F876L mutations that lead to enzalutamide agonism in some cases. However, mechanisms that contribute to the agonist switch have not been fully clarified, and there are no therapies...