Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Glioblastoma (GBM) is the most common and aggressive malignant brain tumour often affecting young, otherwise healthy individuals. It is a type of tumour that starts in glial cells - the most abundant cell type in the brain essential for proper functioning of the nervous system. Patients with GBM are treated with a combination of surgery, radiation, and chemotherapy. Some tumours respond well to therapy, but others become active within months of initial surgical resection and recur. These patients invariably succumb to their disease within a year. Treating GBM is difficult because we do not yet fully understand the underlying biological mechanisms of recurrence. Why do some respond to therapy while others do not? Glioblastoma tumours are very heterogenous, both between patients and within patients, making it difficult to personalize the therapy appropriately. In recent work, we have studied tissue from different tumour regions obtained during initial surgery of GBM patients. We have particularly focused on comparing the bulk of the tumour and the infiltrating cells of the normal brain-tumour border. Due to the infiltrating biology of GBM, complete tumour resection in these patients is impossible. This cancer spreads beyond the layer of tissue in which it originally developed and grows into surrounding, healthy brain tissues. We suspect that the residual, surgically inaccessible malignant cells are therapy-resistant and serve as the seeds of tumour recurrence. In this proposal, we aim to identify the biomarkers that are specific to these infiltrating cells at the "edge" of the tumour. We hypothesize that these cells are spatially segregated and share common features that drive the recurrence. This work will reveal novel treatments and identify predictive markers to allow individual tailoring of the treatment plan of GBM patients to slow down tumour invasion, provide more meaningful period of disease remission, and prevent tumour recurrence following therapy.