OTHR-05. Exploring SLC1A5 in Pediatric Brain Tumors: A Prognostic Biomarker and Target for Therapy and Imaging

Abstract Pediatric brain tumors (PBT) represent a significant clinical challenge, with survival outcomes often dictated by molecular and metabolic adaptations of tumor cells. Among these adaptations, metabolite transporters play a crucial role in sustaining the metabolic demands of proliferating tumor cells. One such transporter, SLC1A5, is a glutamine transporter that has garnered attention for its role in tumor metabolism. Our data shows that SLC1A5 expression is elevated in pediatric brain tumors and associated with clinical time-to-event. Leveraging clinical and transcriptome data from the Children’s Brain Tumor Network (CBTN), we found that high SLC1A5 expression (greater than median cohort expression) is associated with shorter event-free (p = 0.022) and overall survival (p = 0.0039), underscoring its potential as a prognostic biomarker. Mechanistically, SLC1A5 facilitates glutamine uptake, fueling anabolic processes and redox balance critical for tumor growth. To assess the broader impact of SLC1A5 in PBTs, we tested glutamine and glucose deprivation, as well as pharmacological inhibition in vitro. We observed that independent of SLC1A5 expression, there is a high degree of heterogeneity on the reliance of glutamine or glucose for cell growth in these tumor models. Thus, it is imperative to further validate the fate of glutamine uptake via SLC1A5 by PBT cells via metabolite tracing and flux. In addition to its therapeutic implications, SLC1A5 presents opportunities for molecular imaging strategies. Radiolabeled amino acid analogs, such as fluciclovine, have demonstrated promise in non-invasive imaging of glutamine metabolism in tumors. These probes could enable precise tumor characterization, monitoring of therapeutic responses, and stratification of patients for SLC1A5-targeted therapies. This work highlights the dual utility of SLC1A5 in pediatric brain tumors as a prognostic biomarker and a molecular target for therapeutic and diagnostic approaches. Our future research focuses on validating SLC1A5-targeted strategies in clinical trials and exploring its integration into personalized medicine paradigms for children with brain tumors.