Identifying Molecular Markers of Progression to Muscle Invasive Bladder Cancer

An estimated 9,000 Canadians are diagnosed with bladder cancer each year making it the 5th most common cancer in Canada, the 12th most common among women and the 4th among men. Most patients are initially diagnosed with non-muscle invasive bladder cancer (NMIBC), which in some cases can progress to muscle invasive bladder cancer (MIBC). MIBC is associated with significantly poorer prognosis than NMIBC, and it is unclear why some progress to MIBC while others do not. . A collaboration with the computer science department found that an increase in discoidin domain-containing receptor 2 (DDR2) is ninety percent specific for muscle invasion in bladder cancer and that DDR2 is overexpressed in MIBC compared to NMIBC. DDR2 is a tyrosine kinase that functions as a cell surface receptor for collagen and regulates cell differentiation, cell migration, invasion and proliferation. It is also involved in the molecular mechanism of disease progression in thirty six percent of MIBC patients. Furthermore, knockdown of DDR2 in vitro in bladder cancer cell lines decreased cell viability, migration and invasion. The mechanism by which DDR2 mediates progression to MIBC and increases invasion in bladder cancer is currently unknown, and may represent a new target to prevent progression from NMIBC to MIBC. This project will seek to demonstrate that DDR2 can be used as a prognostic indicator for the progression to MIBC and can be used as a therapeutic target preventing progression to MIBC