In vitro and in vivo 1H-MRS to identify the fate of glutamine in Ewing Sarcoma

Motivation: Chemo resistance in Ewing sarcoma (EWS) poses a significant hurdle, especially considering the unclear role of the SLFN11 gene. Uninvestigated metabolic dependencies call for an in-depth exploration to improve treatment effectiveness. Goal(s): This research endeavors to connect metabolic changes in EWS with SLFN11 expression, aiming to identify diagnostic markers that could provide mechanistic insights into therapy design. Approach: Our study integrates metabolomics, transcriptomics, in-vitro nuclear magnetic resonance (NMR), and preclinical magnetic resonance spectroscopy (1H MRS) to examine how SLFN11 influences chemoresistance in EWS, ultimately paving way for metabolism-driven treatments. Results: We found significantly increased glutamine uptake in SLFN-/- EWS cells compared to WT. Impact: Using 1H-MRS, we show that SLFN11 loss increases EWS reliance on glutamine, is different than conventional glutamine metabolism typically observed in other cancers.