Developing new, less toxic approaches to treatment is critical to advancing therapy for medulloblastoma, the most common malignant brain tumor in children. While many medulloblastoma patients achieve long-term survival through combined radiation and chemotherapy, this treatment causes long-term neuro-cognitive impairment and significant risk of incurable recurrence. The early age of onset of medulloblastoma has prompted a growing consensus to examine the processes that support developmental brain growth as potential oncogenic mechanisms that may be targeted in novel therapies. Our recent work demonstrates that energy metabolism, DNA repair and control of apoptosis are developmentally regulated to support proliferation during cerebellar growth, and become co-opted in medulloblastoma formation. Our ongoing projects build on these observations, using mouse genetics and primary tumor modeling to learn:
- How aerobic glycolysis during cerebellar development supports normal and neoplastic growth
- How DNA repair and apoptotic mechanisms converge to prevent tumorigenesis
- How these mechanisms may be targeted for novel anti-cancer therapies.