Epidermal growth factor receptor: a key manipulator in molecular pathways of malignant glioma

Abstract

Abstract The epidermal growth factor receptor (EGFR) is a member of the ErbB/EGFR family, including EGFR/Her1, ErbB2/Her2, ErbB-3/Her3, and ErbB-4/Her4. EGFR exerts its effects through the receptor tyrosine kinase phosphorylation and activation of important downstream signaling pathways in normal and neoplastic cells, mainly the Ras GTPase/MAP kinase (MAPK), STAT3, and phosphatidylinositide 3 kinase-AKT pathways. EGFR deregulation is common in malignant glioma, especially primary glioblastoma, and exists in three forms: gene overexpression (amplification), autocrine effects of EGFR activation, and activating receptor mutation (EGFRvIII). However, some EGFR abnormalities have also been found in low-grade gliomas, including the nuclear localization of EGFR, expression in the microfoci of anaplastic transformation, and association with neovascularization in the mesenchyma of the glioma, which suggests that some unknown EGFR-related mechanisms are possibly responsible for its central role in the initiation and progression of malignant glioma. Uncovering these mechanisms will have potential value in the development of radiotherapy, chemotherapy, and EGFR-targeted therapy for glioma.