MODL-20. Metabolic rewiring support the onset of chemotherapy resistance in medulloblastoma

Abstract Medulloblastoma (MB) is the deadliest brain tumor of childhood, intrinsically characterized by fast growth, high invasiveness, and resistance to treatments. With aim deepen molecular basis MB aggressiveness recurrence, we established an in vitro model chemotherapy, which, a weekly exposure cocktail chemotherapeutics commonly used treatment (Vincristine, Etoposide, Cisplatin, Cyclophosphamide – VECC) induces selection cells that progressively acquire subsequent VECC Preliminary data on our show resistant induce activation two main regulator pentose phosphate pathway TKT G6PD via Nrf2 transcriptional activity. Moreover, increase hypoxia inducible factor-1α (HIF-1α) together with augmented expression glycolytic enzymes HK1, PFKB-3, PDK1 LDHA increased capacity. Interestingly, enrichment analysis label free mass spectrometry reveal most significant terms deriving from upregulated proteins, cells, were related metabolic processes such as “carbon metabolism”, “fatty acid beta oxidation”, “tricarboxylic cycle” “carboxylic catabolic processes”.Consistently recent studies highlight relevance plasticity cancer chemotherapy adaptation, suggest uncoupling which through alteration peculiar processes, may satisfy their altered energetic demands alternative pathways. In this way, generation new balance intracellular metabolites finally provide external insults (i.e., chemotherapeutics) greater ability detoxifying compartments.