ARN-509 is a clinical stage, nonsteroidal antiandrogen discovered in an effort to identify full androgen receptor (AR) antagonists in the setting of AR overexpression, a key determinant of acquired resistance to first generation antiandrogens. ARN-509 exhibits robust antitumor activity in the clinically validated LNCaP/AR model of castration-resistant prostate cancer (CRPC), resulting in tumor regression via a decrease in proliferation and increase in apoptosis. The cover shows a hematoxylin and eosin stained tissue section from a LNCaP/AR xenograft tumor following ARN-509 treatment. There is significantly reduced cellularity with increased deposition of extracellular matrix compared to vehicle treatment. Based on preclinical efficacy coupled with its excellent pharmacokinetic properties and high therapeutic index, ARN-509 has entered clinical development in men with CRPC. For details, see the article by Clegg and colleagues on page 1494 of this issue.