Epidermal growth factor receptor (EGFR) and Human epidermal growth factor receptor 3 (HER3) (EGFR and HER3)

Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3) are cell surface receptor tyrosine kinases belonging to the ERBB family. EGFR is catalytically active, while HER3 has impaired kinase function but serves as a crucial allosteric activator when dimerized with EGFR or other HER family members. Their dimerization triggers downstream oncogenic signaling via the PI3K/AKT and MAPK pathways, driving cell proliferation and survival. Overexpression, mutation, or aberrant activation of these receptors is implicated in numerous cancers and is strongly associated with resistance to targeted therapies. HER3 plays a prominent role in mediating resistance to EGFR-targeted agents, especially in non-small cell lung cancer, by forming heterodimers that perpetuate signaling even when EGFR is inhibited. Numerous drugs target EGFR directly; targeted HER3 therapies are in development or experimental phases. Because of their non-redundant but collaborative roles, the EGFR/HER3 axis is a major focus for combination or multi-target drug strategies in oncology.

Other names

ErbB1HER1ErbB3ERBB family

Inhibition of receptor tyrosine kinase activity; Disruption of homo- and heterodimerization; Antibody-dependent cellular cytotoxicity; Inhibition of ligand binding; Downstream signaling blockade (especially PI3K/AKT and MAPK pathways)