Does Glioblastoma arise from Oncogenic Transformation of Neural Stem Cells into Cancer Stem Cells?

Glioblastoma, the most common and aggressive adult brain malignancy, is characterized by the presence of morphologically diverse neural cell types that differ in their ability to form and maintain tumours. The marked resistance of this cancer to conventional treatments has sparked attempts to identify therapeutically targetable cellular populations. Defined pools of tumour initiating cells have already been identified in other malignancies, i.e., leukemia. Like normal stem cells, these “cancer stem cells” (CSCs) have extensive self renewal capacity and multipotency; however, the origin of the CSC remains elusive. Recently, a small percentage of quiescent, undifferentiated, multipotent cells termed neural stem cells (NSCs) were found in the hippocampus, sub‐ventricular zone (SVZ), and olfactory bulb of the adult human brain. Since their discovery, it has been hypothesized that NSCs may act as a depot of tissue‐specific stem cells in the brain that may be transformed into CSCs. The purpose of this essay is to critically review the literature to demonstrate that oncogenic mutations in NSCs allow them to become CSCs in glioblastomas, in light of the advantages and flaws of existing experimental models. Insights into the mechanism of CSC formation in the brain may allow for the optimization of current therapeutic approaches, as pathways in NSC-->CSC formation will provide opportunities to specifically target this notoriously treatment‐resistant malignancy.