# Imaging the effects of treatment with TERT and EGFR inhibitors on glioblastoma: An MR study

## TL;DR

This study shows that combining EGFR and TERT inhibitors in glioblastoma treatment improves tumor growth inhibition and survival, with early metabolic changes detectable via MRI.

## Contribution

The study introduces combination EGFR/TERT inhibition as a novel treatment strategy with early metabolic biomarkers for glioblastoma.

## Key findings

- Combination treatment with EGFR and TERT inhibitors enhanced tumor growth inhibition and animal survival.
- Metabolic changes, including reduced lactate levels, occurred before tumor size changes.
- Reversal of metabolic biomarkers was linked to tumor recurrence.

## Abstract

Telomerase reverse transcriptase (TERT) promoter mutations are observed in most glioblastoma (GBM) tumors, leading to TERT expression, which is crucial for tumor growth. Accordingly, inhibiting TERT or its upstream tumor-specific transcription factor GA-binding protein transcription factor subunit beta 1 (GABPB1) was shown to inhibit tumor growth. In addition, epidermal growth factor receptor (EGFR) was shown to signal upstream of TERT and GABPB1 and to control TERT expression, and EGFR inhibition also inhibits GBM growth.

This study investigated the individual as well as combined effects of EGFR, TERT, and GABPB1 inhibition on cell and orthotopic rat models. We assessed cell proliferation, animal survival, tumor size, 1H magnetic resonance spectroscopy (MRS)-detectable steady-state lactate, and 13C MRS-detectable hyperpolarized (HP) lactate production.

When TERT or GABPB1 were inhibited simultaneously with EGFR, the combination treatment resulted in enhanced inhibition of cell and tumor growth as well as animal survival compared not only to controls but also to any of the single treatments. Our study also found that steady-state 1H MRS-detectable lactate and HP 13C MRS-detectable lactate production dropped following every treatment, and the drop was significantly greater following combination treatments. Furthermore, the metabolic changes occurred prior to changes in tumor size, and a reversal of these metabolic biomarkers was associated with tumor recurrence.

Our study points to the value of steady-state 1H MRS-detectable lactate and HP 13C MRS-detectable lactate as potential biomarkers of response to combination EGFR/TERT inhibition.