Optimization of Drug Efflux and Brain Clearance to Improve CED of Targeted Therapy to H3K27M DMG

Brain tumors are the leading cause of cancer-related deaths in children. Amongst those, high-grade brainstem tumors known as diffuse midline gliomas, are the most aggressive and uniformly deadly. Radiation therapy is the only treatment option, but only extends life a few months. Most children typically succumb to disease within 12 months of diagnosis. Attempts at chemotherapy have failed in part due to the blood brain barrier, which prevents drugs from getting to the tumor. Therefore, methods to deliver drugs by bypassing the blood brain barrier are of great interest. Convection-enhanced delivery overcomes the blood brain barrier through a direct injection under a pressure gradient into the tumor region. This technique has been shown to be safe in children with these tumors but has not yet achieved its maximum therapeutic potential.