Endocannabinoid signaling in glioma

Abstract

High-grade gliomas constitute the most frequent and aggressive form of primarybrain cancer in adults. These tumors express cannabinoid CB1and CB2receptors, aswell as other elements of the endocannabinoid system. Accruing preclinical evidencesupports that pharmacological activation of cannabinoid receptors located on gliomacells exerts overt anti-tumoral effects by modulating key intracellular signaling path-ways. The mechanism of this cannabinoid receptor-evoked anti-tumoral activity inexperimental models of glioma is intricate and may involve an inhibition not only ofcancer cell survival/proliferation, but also of invasiveness, angiogenesis, and the stemcell-like properties of cancer cells, thereby affecting the complex tumor microenvi-ronment. However, the precise biological role of the endocannabinoid system in thegeneration and progression of glioma seems very context-dependent and remainslargely unknown. Increasing our basic knowledge on how (endo)cannabinoids act onglioma cells could help to optimize experimental cannabinoid-based anti-tumoraltherapies, as well as the preliminary clinical testing that is currently underway.