It has been demonstrated that the AKT/mTOR signaling pathway is critical for the maintenance of the properties of glioma CSCs36, 48; on the other hand, in the same cells the MEK-ERK signalling is required for MDM2 expression, which prevents p53 activation and subsequent suppression of O(6)-methyl-guanine DNA methyltransferase expression, thus contributing to TMZ resistance51. This evidence concerns the gene TP53 and central nervous system cancer.