Therapeutic Targeting of H3K27M-Driven Folate Metabolism in DIPGs

H3K27M Diffuse Midline Gliomas (DMGs) including Diffuse intrinsic pontine gliomas (DIPGs) are lethal brain tumors with a universally poor prognosis1,2. Current treatments are not effective, leading to emergence of resistance and uniform lethality. Hence, there is an immediate and unmet need to develop effective therapies. Our previous research has shown that H3K27M-DIPGs profoundly rewire their metabolic needs to sustain growth and survival5. Our current proposal aims to investigate one such important metabolic pathway that is hijacked by the H3K27M DIPGs to maintain a favorable epigenetic state and mediate radiation
resistance. Our proposed research will a) unravel key tumor promoting roles of this pathway and, crucially, b) facilitate the development of targeted therapies in the future.