Game Changer Grant Awarded to Sriram Venetti

DIPG are fatal tumors without effective treatments and 90% of patients die within 1.5 years of diagnosis. Most therapies used in adults or other types of childhood cancers either produce no effect or only marginally improve survival for DIPG patients. Therefore, research is urgently needed to develop effective therapies. Cancer cells exhibit aberrant and accelerated metabolism that can be leveraged to kill
tumor cells. We have discovered that the frequently-found histone H3K27M mutation (~80%) in DIPG changes how DIPG metabolize nutrients and use metabolic pathways to modify genetic material. We aim to target this metabolic process as a potential therapy that simultaneously tackles two dysfunctional pathways in DIPGs, thus improving chances of therapeutic success. We propose a research program that will (a) help uncover a critical but yet uncharacterized central metabolic pathway in DIPG tumor cells, and (b) provide the groundwork for innovative therapies that simultaneously interrupt two critical and interrelated pathways in DIPGs.