296 (PB076) - Cellular hormone metabolism is critical for canonical androgen receptor antagonist activity

Abstract

Background: Second-generation androgen receptor (AR) antagonists and an androgen synthesizing enzyme inhibitor have become the standard of care for advanced prostate cancer (PCa). Clinically-approved AR antagonists bind to the AR ligand binding domain (LBD) and competitively inhibit AR function. Dual action AR inhibitors (DAARIs), which bind to the N-terminal domain (NTD) of the AR inhibit AR signaling and lead AR protein degradation, have been identified by our group as potential therapeutics for PCa.