Poster #005
Metabolic Effects of ONC206 in EGFR-Mutant Diffuse Midline Glioma
Mentors: Dr. Georgios Batsios, PhD (Mentor), Dr. Pavithra Viswanath, MD, PhD (PI)
Diffuse midline glioma (DMG) is a highly aggressive and incurable brain tumor that is found in children. DMG grows primarily in areas such as brainstem, making surgery nearly impossible and limiting treatment options. Currently the imipridone drug ONC206 is under clinical trials for DMG patients, still there are patients that do not respond. This resistance is often due to a mutation in the Epidermal Growth Factor Receptor (EGFR). We examined how this EGFR mutation affects lactate production in DMGs in combination with ONC206 treatment. Patient-derived cells were genetically modified to express wild type or mutant receptor. Cells were cultured in 2H-glucose media. Nuclear magnetic resonance spectra were acquired using a 600MHz spectrometer and lactate was quantified. ONC206 led to a reduction in lactate level in wild type cells and not in mutants, providing a potential non-invasive biomarker of ONC206 resistance. These results must be confirmed in in vivo models.