EXTH-13. COMBINED TARGETING OF TELOMERASE REVERSE TRANSCRIPTASE AND METABOLISM ABROGATES GLIOBLASTOMA PROLIFERATION IN VIVO

Abstract Telomerase reverse transcriptase (TERT) is essential for tumor immortality. Since TERT silenced in normal cells, it an attractive therapeutic target and the inhibitor 6-thio-2’-deoxyguanosine (6-thio-dG) clinical trials gliomas. However, there a lag period following inhibition before shrinkage observed. Novel strategies that can be combined with to enhance anti-tumor activity are sorely needed. We previously demonstrated increases expression of alanine transporter ASCT2 gliomas, effect could non-invasively monitored using hyperpolarized 13C imaging metabolism (Viswanath et al., Nature Communications, 2021). The goals current study were determine whether inhibits GBM growth assess ability [1-13C]-alanine monitor treatment response. Our results indicated that, while both 6-thio-dG V-9302 individually inhibited viability, combination maximally cell viability patient-derived GBM1 GBM6 models. In line on compounds reduced lactate production from [1-13C]-alanine, resulted highest Importantly, rats bearing orthotopic tumors caused shrinkage, visualized by magnetic resonance day 21 after treatment. Furthermore, was significantly at 7 V-9302, when anatomical alterations absent. Collectively, our indicate simultaneously targeting provides novel opportunity GBMs serves as companion agent early response therapy. findings pave way precision therapy assessment patients.