The simplest explanation rests in the possibility that ZOL acts as a Ras inhibitor and blocks the activation of Ras and its downstream signaling such as MAPK and Akt, which are frequently activated in malignant gliomas and suppress TMZ-induced cytotoxicity against malignant glioma cells (Fig. 4) [19], [20]. Here, AKT1 is linked to malignant glioma.