Grant: Operating Grant

Once prostate cancer becomes castrate-recurrent there are no effective therapies that can be offered and the patient will succumb to his disease in approximately two years. There is mounting evidence supporting the concept that development of castrate-recurrent disease is causally related to molecular changes affecting the function of the androgen receptor. All current hormonal therapies target the C-terminus ligand-binding domain of the androgen receptor and include androgen ablation and antiandrogens. We have identified EPI-001, a specific small molecule inhibitor to the N-terminus of the androgen receptor which represents a new mechanism of pharmacologic specificity. EPI-001 causes regression of prostate cancer tumours without any significant toxicity in preclinical animal models. The mechanism of action has been characterized for EPI-001. Here we propose to examine known mechanisms of resistant for current antiandrogens to determine if EPI-001 could be used in patients that develop resistant to current therapies. In addition, EPI-001 will be tested in combination with other therapeutic approaches used clinically.