EGFR and glioblastoma: It has been found that the over-expression of EGFR in humans accounts for 40%–60% of primary GBM tumors, especially in the classical subtype (146), however, the over-expression of EGFR in GBM is intrinsically implicated in gain-of-function missense mutations and in-frame deletions in the extracellular domain, rather than responsiveness to EGFR inhibitors (147, 148).