Abstract: Using microarray-based profiling of isogenic prostate cancer xenograft models, we found that a modest (2-5 fold) increase in androgen receptor (AR) mRNA was the only expression change consistently associated with developing resistance to antiandrogen therapy. Increased levels of AR confer resistance to anti-androgens by amplifying signal output from low levels of residual ligand and altering the normal response to antagonists. This invention provides cell based assays for use in the examination of new therapeutic modalities and provides insight toward the design of novel antiandrogens.

Abstract: The present invention relates to diarylhydantoin compounds, including diarylthiohydantoins, and methods for synthesizing them and using them in the treatment of hormone refractory prostate cancer.