EGFR / ERBB1 / HER1 - SPR Binding Assay

Theoretical background: The epidermal growth factor receptor (EGFR) is part of the erbB family of receptor tyrosine kinases, including HER2/erbB2, HER3/erbB3 and HER4/erbB4. Activation of ErbB receptors is initiated by ligand binding to their extracellular domain, leading to the formation of both, homo- and heterodimeric ErbB receptor complexes. Upon dimerization the receptor kinase undergoes autophosphorylation at specific tyrosine residues within the intracellular domain, acting as binding sites for proteins e.g. Shc, Grb2 resulting in activation of signaling pathways such as Ras-ERK, phosphoinositide-3 kinase, Src, and STAT. Deregulated EGFR signaling, caused by overexpression of the receptor or an enhanced ligand production, is frequent in many tumor types.

EGFR and inhibitors: Different drug classes targeting EGFR have been developed. Monoclonal antibodies are able to bind the extracellular ligand-binding domain (Cetuximab, Panitumumab) inducing receptor internalization and degradation. Small molecules targeting the tyrosine kinase domain (Gefitinib and Erlotinib, IC₅₀ = 23 nM [1] and 2 nM [2]) prevent signal transduction and have shown promise as chemotherapeutic agents.