An in-vitro deuterium NMR study to measure the efficacy of combinatorial therapy for diffuse intrinsic pontine glioma

Motivation: There is a need for developing next generation of clinical trials by targeting selective pathways in diffuse intrinsic pontine glioma (DIPG). Goal(s): We explore the impact of Vehicle (DMSO), Paxalisib, BAY-876, and their combination in patient-derived SJ-DIPGX7 cell line to evaluate their potential as a therapeutic strategy for patients with DIPG. Approach: 2H-NMR spectra were longitudinally obtained in a cell suspension. We calculated the lactate flux turnover, which was validated using 100-run Monte-Carlo simulation. This outcome was further confirmed by conducting a glycolysis stress test. Results: The combined therapy (Paxalisib + BAY-876) holds potential for enhancing its therapeutic effectiveness against DIPGs. Impact: This study paves the way for future in-vitro and in-vivo studies to be conducted for monitoring efficacy of targeted therapeutic combination for DIPG.