Epidermal growth factor receptor–Hepatocyte growth factor receptor extracellular interface (EGFR–MET interface)

The Epidermal growth factor receptor–Hepatocyte growth factor receptor (EGFR–MET) extracellular interface is a functional and structural site involving the co-localization and interaction of EGFR and MET on the plasma membrane. This interface is a critical therapeutic target in oncology, particularly in non-small cell lung cancer (NSCLC), because MET signaling frequently serves as a bypass mechanism for resistance to EGFR-targeted therapies (UniProt P00533, P08581). Bispecific antibodies like amivantamab are designed to bind this interface, simultaneously blocking the binding of ligands such as epidermal growth factor (EGF) and hepatocyte growth factor (HGF). This dual blockade inhibits downstream oncogenic pathways, including MAPK and PI3K/Akt, which drive tumor growth and survival (Yun et al., Cancer Discovery, 2020). Additionally, targeting this extracellular site facilitates receptor down-regulation through lysosomal degradation and triggers immune-mediated tumor cell killing via antibody-dependent cellular cytotoxicity (ADCC) (Park et al., JCO, 2021). This approach is specifically effective against tumors with EGFR exon 20 insertion mutations or those that have developed resistance to third-generation tyrosine kinase inhibitors (FDA, 2021).

Other names

EGFR-MET complexEGFR-c-Met interfaceEGFR-MET heterodimerization sitec-Met-EGFR interface

Bispecific binding to the extracellular domains of EGFR and MET, leading to inhibition of ligand binding, receptor internalization/degradation via trogocytosis, and induction of antibody-dependent cellular cytotoxicity (ADCC).