The mechanisms underlying the differential activation of p53 upon the inhibition of MDM2 in the absence of external stimuli currently remain unknown; however, the intracellular milieus associated with the stem cell status may generate p53-activating signals that need to be actively counteracted by the overexpression of MDM2 for glioma stem cells to evade p53-dependent apoptosis. Here, MDM2 is linked to central nervous system cancer.