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 regimens 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 for children with DIPG. Cancer cells exhibit aberrant and accelerated metabolism that can be leveraged to kill tumor cells. We have discovered that DIPG cells are addicted to glucose in order to provide energy to support their uncontrolled proliferation. Surprisingly, DIPG tumor cells also use glucose to modify a canonical mutation found in more than 80% of DIPGs. Targeting this pathway constitutes a potential therapy that simultaneously tackles two dysfunctional pathways in DIPGs, thus improving chances of therapeutic success by overcoming the ability of cancer cells to resist treatment via redundant biological pathways. We propose a research program to define the role of and dependence on glucose in DIPG. Our work will (a) help uncover a critical but yet characterized central pathway in DIPG tumor cells and (b) provide the groundwork for innovative therapies that simultaneously interrupt two critical and interrelated pathways in DIPGs.