Grant: Project Grant

Glioblastomas are deadly brain cancers that are on the rise, with the incidence doubling over the last 20 years. While these tumours rarely spread outside the brain, they invade surrounding normal brain tissue, making treatment difficult and recurrence inevitable. Thus, despite being aggressively treated, most patients with glioblastoma die within 15 months. It is clear that new approaches are needed if we are to make a significant impact on clinical outcome. We propose that a better understanding of the environment in which glioblastomas grow, especially in the context of the omega-3 and omega-6 fatty acids, will provide key information that can be used to control the growth of this extremely aggressive and deadly brain cancer. We and others have found that brain fatty acid binding protein (FABP7) is associated with a worse prognosis in glioblastoma. Subsequent work in my lab showed that FABP7 is a stem cell marker present in all glioblastoma neurosphere cultures derived from patients. What's important about these neurosphere cultures is that they represent the "cancer stem cell" component of glioblastoma, and are believed to be the drivers of glioblastoma recurrence. Importantly, we are able to reduce the aggressive properties of FABP7-positive glioblastoma cells by increasing the amount of the fat that binds FABP7, omega-3 DHA, in the medium in which the glioblastoma cells are growing. The goal of this grant proposal is to figure out how FABP7 uses fatty acids such as DHA to control the spread of glioblastoma tumours. We will use a combination of approaches to examine how FABP7, when in the presence of DHA or other types of fats, promotes or inhibits glioblastoma spread. We will also examine whether manipulation of FABP7 and DHA can be used to sensitize glioblastoma tumours to radiation and chemotherapy. Our experiments will be carried out using patient-derived glioblastoma cells and pre-clinical models of glioblastoma.