Grant: Project Grant

Glioblastoma is the most common malignant brain tumor in adults. Despite surgery, radiation, and chemotherapy, most patients survive 15-18 months, which has not improved in over 40 years. The problem is that glioblastoma always recurs, typically within 7-8 months. Scientists have extensively analyzed the tumor that surgeons remove to better understand how glioblastoma evades therapies. However, this removed tissue is not what causes recurrence. Instead, recurrence grows from cells left behind that survive in normal brain, hide from detection, and resist treatment. Because glioblastoma is extremely varied from region to region, we believe these "cells left behind" are fundamentally different from the bulk tumor that gets removed and from which we develop therapies. It is possible then that the therapies we create are targeting things that aren't critical to the patient. Our project will systematically study the cells left behind that drive recurrence using two unique surgical approaches. First, rare specimens where entire brain regions are removed with the tumor will let us study how tumor cells invade into normal brain and whether the local brain environment shapes their behavior. Second, we developed a biopsy device that samples the surgical margins and tracks these exact locations on follow-up brain scans to see which spots later develop recurrence. Finally, we built a system where different cell types produce different colors of light, so we can watch in real-time how cell populations change in response to chemotherapy, radiation, and contact with normal brain cells, revealing how treatment-resistant populations emerge. This work will guide smarter clinical trials and better patient care. By identifying where recurrence is likely to start, doctors can personalize radiation treatment. By understanding how resistant populations emerge during therapy, we can identify when and how to intervene to prevent recurrence rather than waiting to treat after it occurs.