Abstract
Prostate cancer (PCa) is the second most common cause of cancer-related death among men, with around 218,000 new cases annually and 27,000 deaths. Most prostate cancer is hormone dependent and is treated with androgen deprivation therapy (ADT). When combined with an antiandrogen this combination results in complete androgen blockade (CAB). If the disease progresses to castration-resistant prostate cancer (CRPC) CAB is no longer effective; this failure of therapy is commonly associated with increased levels of AR expression, through various mechanisms, which have been shown in mouse xenograft models to be necessary and sufficient to confer resistance to antiandrogen therapy. Tran and Ouk et al. have recently published a paper characterizing two novel antiandrogens, RD162 and MDV3100, which retain activity even under increased androgen expression that is seen in most CRPC. RD162 and MDV3100 suppress growth of PCa cell lines in vitro and in vivo, with a decrease in tumor volume compared to bicalutamide in an AR overexpressing cell line. A benefit was also seen with an increase in median times to progression of 151 days for RD162 compared to bicalutamide. In an in vitro experiment employing the LNCaP/AR cell line, induction of PSA and TMPRSS2 was only seen with bicalutamide treatment.