Glioblastoma (GBM) is one of the most aggressive and common brain tumors in adults. Current treatments have failed to extend median survival time beyond 15 months, indicating an urgent need for a more effective GBM therapy. To achieve this goal, scientists must better understand the molecular machinery that drives GBM. Recent work indicates that a subset of GBM tumors show elevated activity of a protein known to affect tumor growth called epidermal growth factor receptor (EGFR). Tumors with overactive EGFR also have enhanced activity of another protein called HER2. AZD9291 — a compound that can cross the blood-brain barrier and was originally designed to treat lung cancer — blocks the activity of both EGFR and HER2. The proposed studies are designed to find an effective therapy for glioblastoma patients with an activated form of EGFR. This work could lead to the development of a new, more effective and more precise treatment strategy for a specific group of GBM patients.