The androgen receptor (AR) is critical to the growth and proliferation of nearly all prostate cancers. Once activated, the AR binds to cis-regulatory elements on DNA that drive gene expression. Yet, how this occurs is poorly understood as there are 10–100× more binding sites than differentially expressed genes. Further, these AR binding sites work through a complex network of three-dimensional chromatin loops that bring the AR protein in physical contact with other transcription factors, co-regulatory proteins, and cis-regulatory elements. In this talk we determine how these interactions contribute to AR activity in late-stage prostate cancer in an effort to identify potential therapeutic vulnerabilities.