Mitochondrial poisoning as a novel therapy for glioblastoma

BACKGROUND: Glioblastoma (GBM) is the most common and lethal adult brain tumour. Increased oxidative phosphorylation is observed in orthotopic GBM mouse models and in human GBM, suggesting that targeting mitochondrial function might be a promising strategy in this disease. The mitochondrial inhibitor ME-344 (MEI-Pharma) has shown activity in pre-clinical in vivo models of ovarian cancer and improved progression-free survival in early phase human clinical studies in small cell lung cancer. The aim of our study was to investigate therapeutic activity and mechanisms of action of ME-344 in preclinical models of GBM. Materials and Methods: Experiments were performed on three GBM cell lines (patient-derived cell lines E2 and G7, and the established cell line U87MGLuc2) grown in stem-cell enriched conditions in conventional two-dimensional (2D) cultures, a clinically relevant 3D in vitro model of …