Initiation of EGFR signaling by ligand binding (which is exacerbated in GBM cells over-expressing EGFR) or gene mutation (i.e., EGFRvIII) results in activation of the PI3K/AKT/mTOR pathway with the subsequent up-regulation of HIF-1α (Figure 2A) [52,53]. Here, EGFR is linked to glioblastoma.