Grant: Operating Grant

Breast cancer is the most commonly diagnosed cancer affecting Canadian women and is the second leading cause of cancer deaths in these patients. This is a complex disease composed of many forms of breast cancer, each possessing different characteristics with respect to patient prognosis and response to therapy. Once breast cancer cells have spread to other organs, the disease is largely incurable. Breast cancer metastasis currently represents an intensive area of investigation to better understand the mechanisms contributing to the ability of tumor cells to thrive in diverse and foreign microenvironments. We have identified a protein, called GPNMB, which promotes breast cancer growth and helps breast cancer cells become invasive and metastatic. Using mouse models, we have shown that breast cancer cells expressing high levels of GPNMB are better able to spread to the bones and lungs when compared to cells that do not express this protein. We have also found that primary tumors from breast cancer patients express high levels of GPNMB and are associated with a very aggressive type of cancer for which no targeted therapies currently exist. Novel therapeutic agents are being developed to target this protein in cancer, and clinical trials designed to test the efficacy of these agents in patients with breast cancer are now underway. Despite the clinical importance of this protein in breast cancer, little is known about the mechanisms through which it exerts its metastatic effects. The experiments outlined in this research proposal will employ cell culture and animal models to further characterize the ability of GPNMB to promote breast cancer progression and metastasis. We will also identify proteins that associate with and regulate GPNMB-mediated biological functions. Finally, we will investigate strategies to enhance the efficacy of currently available therapeutic agents that are being used to target GPNMB in metastatic breast cancer.