Human epidermal growth factor receptor family (HER family) (HER family)

The Human epidermal growth factor receptor (HER) family, also known as the ErbB family, consists of four structurally related transmembrane receptor tyrosine kinases: EGFR (HER1), HER2 (ErbB2), HER3 (ErbB3), and HER4 (ErbB4) (UniProt P00533, P04626; StatPearls). These receptors are critical regulators of cell growth, survival, and differentiation, functioning through the activation of intracellular signaling pathways such as MAPK/ERK and PI3K/Akt (NIH NCI; PubMed PMID: 20602996). While EGFR, HER3, and HER4 are activated by specific ligands, HER2 exists in a constitutively active conformation and acts as a preferred dimerization partner for other family members (PubMed PMID: 15229194). Aberrant signaling due to gene amplification or mutation is a hallmark of various cancers, including breast, lung, and colorectal malignancies (PubMed PMID: 16286015). Therapeutic intervention involves monoclonal antibodies that block the extracellular domain, small-molecule tyrosine kinase inhibitors (TKIs) that target the intracellular catalytic site, and antibody-drug conjugates (ADCs) for targeted cytotoxicity (FDA; PubMed PMID: 24211477). These treatments have significantly improved outcomes but are associated with specific toxicities like cardiotoxicity and skin rash (StatPearls).

Other names

ErbB receptor familyEpidermal growth factor receptor familyType I receptor tyrosine kinase familyErbB family

Inhibition of extracellular ligand binding, prevention of receptor homo- and hetero-dimerization, and competitive inhibition of the intracellular ATP-binding site of the tyrosine kinase domain.