EGFR and glioblastoma: However, rather than RAS mutations, activation of this pathway in GBM is frequently due to amplification or constitutive activation of receptor tyrosine kinases including Epidermal Growth Factor Receptor (EGFR) and Platelet Derived Growth Factor Receptor (PDGFR): further elevation of ligands and/or receptors under hypoxia influences even greater activation of the RAS/MAPK signaling pathway 224, 226, 227.