Grant: Project Grant

Prostate cancer is the most common male malignancy in Canada. The disease affects one in six men and is the second leading cause of cancer-associated deaths in Canadian men. Mortality is mainly caused by disease progression on the standard of care: androgen deprivation therapy. Since the 1940s, androgen deprivation is the first line therapy used in patients with advanced prostate cancer. This treatment temporarily stops prostate cancer growth. However, resistant tumors in the form of castration resistant prostate cancers (CRPCs) always arise, and are lethal. CRPC is the dominant cause of prostate cancer death. Understanding what causes CRPC development is critical to offer patients the best medical care. Our group has recently found a protein that promotes CRPC development. The expression of this protein is increased in prostate cancers metastasized to the bone. Bone is the major site of prostate cancer metastasis; prostate cancers metastatic to bone are the dominant source of CRPC. Furthermore, we found that prostate cancers with higher levels of this protein are likely to progress to CRPC. Importantly, using mouse models for human CRPC, we have shown that by increasing the level of this protein expression alone is sufficient to convert castration-sensitive prostate cancer cells to cells resistant to castration. Collectively, our research suggests this protein being an important contributor to CRPC development in human prostate cancer. In this project, we will thoroughly examine this protein's contributions to the progression of castration resistant prostate cancers using human prostate cancer cell lines, mouse models for CRPC, and patients' tumor tissues. We will also determine whether by reducing this protein expression will prevent or reduce CRPC development. This research will reveal a new factor that enhances CRPC development. This knowledge will pave the way to develop new means of diagnosis and new treatments in patients with advanced prostate cancer.