EGFR and neoplasm: Challenges to targeting of EGFR include heterogeneity of EGFR mutant and wild-type expression [58,59,111], adverse effects arising from collateral inhibition on wild-type EGFR in normal tissues, reduced penetration of monoclonal antibodies across the blood brain barrier (particularly at the infiltrating edges of the tumor where blood brain barrier is intact), and escape mechanisms such as the PI3K and MET pathways.