Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Prostate cancer is one of the leading causes of cancer-related death in men worldwide. If diagnosed early, prostate cancer is curable by surgery and/or radiotherapy. In cases of locally advanced, recurrent, and metastatic disease, androgen deprivation therapy (ADT) is the standard treatment. ADT aims to either block the production of androgens or block the interaction between the androgen and its receptor, the androgen receptor (AR). While initially effective, resistance to ADT often occurs and with no other curative treatments the life expectancy of the patients is approximately 18 months. A severe limitation to all current anti-AR therapeutics is that they possess similar chemical structures and target the same binding site, which is known to be predisposed to mutations. In our lab we have utilized advanced computer modelling techniques to identify several new candidate drug compounds for an entirely new generation of drugs that target the distinct protein, ERG. In more than 50% of all prostate cancer cases, a genomic irregularity is present between the genes TMPRSS2 and ERG. This alteration results in the overexpression of the ERG protein in the prostate where it acts to promote disease metastasis. The current study aims to understand the mechanisms of action of these candidate anti-ERG compounds in order to develop an entirely new generation of therapeutics that could either supplement or replace the current resistant-prone therapeutics for metastatic, castration-resistant prostate cancer patients.