PDTM-46. TARGETING METABOLIC ADAPTATION IN MYC DRIVEN PEDIATRIC NEURONAL TUMORS

BACKGROUND/OBJECTIVES MYC family proteins are implicated in many human cancers, but their therapeutic targeting has proven challenging. MYCN and c-MYC amplification in childhood neuroblastoma (NB) and medulloblastoma (MB) are associated with aggressive disease and high mortality. Novel and effective therapeutic strategies are therefore urgently needed for these tumors. MYC-driven oncogenic transformation impairs cell survival under nutrient deprivation (ND), a characteristic stress condition within the tumor microenvironment. We recently identified eukaryotic Elongation Factor 2 Kinase (eEF2K) as a pivotal mediator of the adaptive response of tumor cells to ND. We therefore hypothesized that eEF2K facilitates the adaptation of MYCN/MYC amplified NB/MB to ND, and that inhibiting this pathway can impair tumor progression.