In Search of a Breakthrough Therapy for Glioblastoma Multiforme

Abstract

Glioblastoma multiforme (GBM) is an extremely malignant type of brain cancer which originates from astrocytes or their precursors. Glioblastoma multiforme cells share some features with astrocytes but are characterized by highly unstable genomes with multiple driver mutations and aberrations. Effective therapies for GBM are lacking and hardly any progress has been made in the last 15 years in terms of improving the outcomes for patients. The lack of new especially targeted anti-GBM medications has prompted scientists in academia around the world to test whether any of the currently approved drugs might be used to fight this devastating disease. This approach is known as repurposing. Dozens of drugs have been reported to have anti-GBM properties in vitro but there is no solid evidence for the clinical efficacy of any of them. Perhaps the most interesting group of those repurposed are tricyclic antidepressants but the mechanism of their action on GBM cells remains obscure. In this brief review we consider various approaches to repurpose drugs for therapy of GBM and highlight their limitations. We also pay special attention to the mitochondria, which appear to be intimately involved in the process of apoptosis and could be a focus of future developments in search of a better treatment for patients suffering from GBM.