Emerging Lipid Targets in Glioblastoma

Simple Summary Glioblastoma (GBM) is a deadly cancer type of the brain with an average of 12 months of survival after diagnosis. Current clinical therapies generally provide only a short lifetime extension. GBM is embedded in a highly lipid-rich environment, and emerging evidence supports that lipid-based therapeutic molecules are promising research targets to unravel novel drugs. Recent efforts of phase trials suggest that lipid-based combination therapies may offer a survival benefit. Here we review preclinical and clinical antitumor approaches targeting the altered lipid metabolism of glioblastoma.Abstract GBM accounts for most of the fatal brain cancer cases, making it one of the deadliest tumor types. GBM is characterized by severe progression and poor prognosis with a short survival upon conventional chemo- and radiotherapy. In order to improve therapeutic efficiency, considerable efforts have been made to target various features of GBM. One of the targetable features of GBM is the rewired lipid metabolism that contributes to the tumor's aggressive growth and penetration into the surrounding brain tissue. Lipid reprogramming allows GBM to acquire survival, proliferation, and invasion benefits as well as supportive modulation of the tumor microenvironment. Several attempts have been made to find novel therapeutic approaches by exploiting the lipid metabolic reprogramming in GBM. In recent studies, various components of de novo lipogenesis, fatty acid oxidation, lipid uptake, and prostaglandin synthesis have been considered promising targets in GBM. Emerging data also suggest a significant role hence therapeutic potential of the endocannabinoid metabolic pathway in GBM. Here we review the lipid-related GBM characteristics in detail and highlight specific targets with their potential therapeutic use in novel antitumor approaches.