Glioblastoma (GBM) is a deadly brain cancer that has eluded major treatment advances. Previous research methodology of growing stem cells from the brain was pioneered by a lead on this project out of the University of Calgary and a recently established cell-based model system provided this project with the foundation for an innovative drug discovery program with real potential for rapid clinical translation. This project’s experimental strategy begins with brain tumor initiating cell lines as a research tool for drug and target discovery and ends with new therapeutics in early phase human testing in molecularly defined subpopulations of GBM via a collaboration with the NCIC Clinical Trials Group. The team’s approach, which combines a superior model system with high-throughput drug screening and genomics technologies, holds great promise. Overall, the ultimate objective is the discovery of new drug therapies for GBM that will improve tumor control and quality of life for patients with this disease. Support of this application will ensure that a stream of new compounds for GBM is entering human trials in Canada within five years and will ensure that specialized laboratory models of GBM are in hand to support future drug discovery.