This Small Business Innovation Research (SBIR) Phase I project will help develop the first effective therapy for late stage hormone refractory Prostate Cancer (PCa). These late stage tumors rely on the Androgen Receptor (AR) pathway, but do not require androgen. Genetic changes allow tumors to use the pathway but escape the need for the hormone. For these patients current therapy (androgen ablation) has no effect. Innovations are: (1) blocking gene expression of AR pathway downstream of androgen binding so it will be effective for hormone refractory PCa; and (2) the use of an efficient technique to produce the lead compound. Successful completion of the Phase I grant will result in a compound that causes a reduction in size of androgen independent prostate tumors in mice, validating it as the first targeted therapy for recurrent hormone refractory PCa. The broader/commercial impacts of this project are multifold. First, the work focuses on a general phenomenon: late stage Hormone Refractory Disease (HRD). The direct target, PCa, represents a large market (>$3 billion) that remains focused on hormone ablation therapy. No therapies exist that are effective for late stage HRD. This stage kills more than 20,000 men per year in the US alone. Many companies are active in this area and will be our potential partners for commercial development. Secondly, the work also focuses on an economical method to produce a natural product from plants. Natural products make up 60% of the anticancer agents that are commercially available or in late stage clinical development
