Pre-doctoral Fellowship Grant Awarded to Stefanie-Grace Sbergio

Diffuse Intrinsic Pontine Glioma (DIPG) is a lethal pediatric brain tumour with no therapeutic options currently available. Although ongoing research continues to develop our understanding of this disease, we have had limited success developing treatments. As we have come to learn more about DIPG, several studies report increased activity in the RAS/MAPK axis, a pathway that regulates cell survival. Therefore, if we could target these cancer cells and prevent the activation of this pathway, we may kill tumour cells and prevent tumour cell survival. In collaboration with Dr. Roman Melnyk’s group, my project will investigate a targeted toxin that can specifically kill tumour cells by stopping this pathway. By identifying a cell surface receptor specific to tumour cells Dr. Melnyk’s group can construct a molecule that binds to the surface and cleaves RAS to kill these cells thus reducing tumour size. I will be testing these molecules in cells from patient samples as well as in mouse models to support its efficacy and safety. As these molecules are large and potent, they must be delivered directly into the tumour. This means it will require a direct delivery technique such as Convection Enhance Delivery, which is currently used in patients. To test this molecule and technique in a mouse model I will be using an osmotic pump. Using the pump, a catheter can directly deliver the molecule into the brain to the tumour therefore killing tumour cells. By having a treatment that uses both a targeted molecule and a direct delivery technique I believe that this therapy will prolong the lives of DIPG patients, so that it may no longer be lethal.