PharmGKB summary: very important pharmacogene information for the epidermal growth factor receptor

Epidermal growth factor receptor (EGFR) encodes a transmembrane glycoprotein. This protein is a member of the protein kinase superfamily, which consists of EGFR (ErbB1/HER1), HER2 (ErbB2), HER3 (ErbB3) and HER4 (ErbB4). All family members contain an extracellular ligand-binding domain, a single membrane-spanning region, a juxtamembrane nuclear localization signal, and a cytoplasmic tyrosine kinase domain. They are collectively called HER receptors and are ubiquitously expressed in various cell types, primarily in those of epithelial, mesenchymal and neuronal origin. Under homeostatic conditions, receptor activation is tightly regulated by the availability of ligands, which together form the epidermal growth factor (EGF) family [1]. From those ligands, EGF, transforming growth factor alpha and amphiregulin bind specifically to EGFR [2]. Binding of the EGFR or other family members to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. The EGFR involvement in carcinogenesis has been well established and mutations in EGFR can be utilized as predictive markers in the treatment of cancer. In this review, we will focus on the effects of genetic variants (somatic and germline) in the treatment of non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKI) and will provide a pharmacogenomics overview of EGFR in humans. This Very Important Pharmacogene (VIP) summary is available with interactive links to gene variants and drugs on the PharmGKB website http://pharmgkb.org/gene/PA7360 [3].