Grant: Project Grant

Prostate cancer (PCa) is the third primary cause of death from cancer in Canadian men. Roughly 25,900 new cases and 4,900 deaths have been reported in 2023. The hormone androgen and its receptor (AR) are the major drivers of PCa development. Hence, androgen deprivation therapy (ADT) and AR inhibitors are used as standard treatments post-surgery or -radiation intervention. While most patients initially respond well to ADT, the malady eventually progresses toward a poor outcome form of the disease, referred to as castration resistant PCa (CRPC). To stimulate tumour growth in the early stages of tumorigenesis, the AR needs the assistance of other proteins, referred to as transcriptional coregulators. This project will focus on one such factor, HOXB13. The HOXB13 protein is required for proper prostate development, is expressed in all stages of PCa, and men bearing a specific mutation in the HOXB13 gene have a predisposition to develop PCa. However, our knowledge of how HOXB13 promotes the initiation and progression of PCa remains utterly incomplete. Using cellular and newly engineered mouse models developed by our laboratory, we will explore the molecular mechanisms by which HOXB13 influences the initiation and progression of PCa. We envision that modulation of HOXB13 activity may help mitigate the detrimental actions of AR in PCa cells without engendering resistance to ADT, thus avoiding progression to the lethal CRPC stage of the disease.