Nevertheless, in GBM samples, activation of PI3K/Akt/mTOR cascade is observed in almost 90% of the cases, and caused by the overexpression of upstream activators, like epidermal growth factor receptor (EGFR) or c-Met, activating mutations of PI3CA (p110) or PIK3R1 (P85) (148–150), and inactivating mutations in the phosphatase and tensin homolog (PTEN), a negative regulator of PI3K activity (loss-of-function mutations in PTEN are present in almost 60-85% of GBMs) (151, 152). Here, EGFR is linked to glioblastoma.