Cut the fat: targeting cholesterol and lipid metabolism in glioblastoma

In the past decades, much research has been focused on identifying oncogenic signaling events in glioblastoma (GBM). Based on these findings, novel therapeutics have been extensively tested in clinical trials. These include targeted agents (e.g., kinase inhibitors), anti-angiogenic drugs, and immunotherapies. Unfortunately, no survival benefit has been demonstrated with the use of these agents. The lack of efficacy observed in the past decades poses the question of whether we are targeting the right pathways to halt the growth of GBM. In this review article, we discuss the intricacies of cholesterol and lipid metabolism in GBM. We provide an overview of which oncogenic signaling pathways are fueled by the aberrant cholesterol and lipid metabolism in GBM. Importantly, we also discuss how metabolic rewiring in the context of cholesterol and lipids can contribute to immune evasion in GBM. Lastly, we provide an overview of current drugs targeting cholesterol and fatty acid metabolism and their potential to serve as targeted therapies for GBM.