Exploiting AR-Regulated Drug Transport to Induce Sensitivity to the Survivin Inhibitor YM155.

ABSTRACT: Androgen receptor (AR) signaling is fundamental to prostate cancer and is the dominant therapeutic target in metastatic disease. However, stringent androgen deprivation therapy regimens decrease quality of life and have been largely unsuccessful in curtailing mortality. Recent clinical and preclinical studies have taken advantage of the dichotomous ability of AR signaling to elicit growth-suppressive and differentiating effects by administering hyperphysiologic levels of testosterone. In this study, high-throughput drug screening identified a potent synergy between high-androgen therapy and YM155, a transcriptional inhibitor of survivin (BIRC5). This interaction was mediated by the direct transcriptional upregulation of the YM155 transporter SLC35F2 by the AR. Androgen-mediated YM155-induc

SUBMITTER: Nyquist MD 

PROVIDER: S-EPMC5471626 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature