LAUSR

202Background: Recent clinical studies have taken advantage of the dichotomous ability of androgen receptor signaling to elicit growth-suppressive and differentiating effects by giving hyper-physiological levels of testosterone. This approach has demonstrated safety, improved quality of life, and met primary endpoints for efficacy in clinical trials; however, novel strategies to enhance and optimize the anti-tumor efficacy of this approach are needed. Methods: We performed high-throughput drug screening in PCa cell lines to identify agents showing synergy with high-dose androgen treatment. Results: The Survivin inhibitor YM155, demonstrated a potent synergy with high-dose androgen. YM155 IC50 values shifted from 24 nM without R1881 to 3.85 nM with 160 pM R1881.Using qRT-PCT and ChIP-qPCR we establish the mechanism of this synergy was due to the direct upregulation of YM155 transporter SLC35F2 by androgen receptor transcriptional activity. Knockdown and overexpression of SLC35F2 dramatically modulated sens...