The PI3K/Akt/mTOR signaling is constitutively activated in most GBMs, resulting in the constant activation of prosurvival signals, with the blocking of tumor suppression pathways, so that the inhibition of these two pathways in conjunction with p53 activation may have the ability to induce cell death in GBMs and differentiation of GSCs, as previously suggested by Daniele et al. [24]. The gene discussed is TP53; the disease is neoplasm.