Investigation of 1H and hyperpolarized 13C spectroscopy-based biomarkers for dual inhibition of TERT and EGFR in GBM cell and animal models.

Motivation: Inhibiting TERT or its upstream transcription factor GABPB1 can result in tumor growth inhibition. Inhibiting EGFR, upstream of TERT, can also reduce TERT expression. Goal(s): Investigating the combined effects of EGFR and TERT inhibition and assessing whether our MRS-based biomarkers can detect the impact of this combination therapy in cell and animal models. Approach: Proton and hyperpolarized 13C spectroscopy in cell and animal modelsResults: Enhanced inhibition of both cell and tumor growth was observed in our GBM models when TERT/GABPB1 and EGFR were targeted simultaneously. This was associated with a drop in hyperpolarized lactate production from pyruvate. Impact: This study identifies HP lactate as a metabolic biomarker of response to the dual TERT/GABPB1 and EGFR inhibition in cells and animals and points to the value of this biomarker in detecting the added value of this novel combination therapy.