Targeting the Epidermal Growth Factor Receptor in Bladder Cancer

Abstract

The Epidermal Growth Factor Receptor (EGFR), or ErbB1, is a member of the ErbB family of tyrosine kinase receptors. It is a 170 kDa transmembrane glycoprotein that can bind a variety of ligands on its extracellular domain, most notably Epidermal Growth Factor (EGF). Binding of ligand induces homo- or heterodimerization with a second EGFR molecule or another member of the ErbB family, respectively. Once dimerized, the molecule undergoes auto-phosphorylation on intracellular tyrosine residues. Phosphorylation of these tyrosine residues allows for recruitment of ATP to the catalytic kinase domain of EGFR, which allows for phosphorylation of effector molecules. Thus, a phosphorylation cascade is set off, leading to activation of various intracellular signaling pathways that have been implicated in tumorigenesis and cancer progression, including the RAS/MAPK (mitogen-activated protein kinase), PI3K (phosphoinositide 3-kinase)/ AKT, and STAT3 (signal transducer and activator of transcription 3) pathways