Epidermal growth factor receptor family (EGFR, HER2, HER4) (ErbB family)

The Epidermal Growth Factor Receptor (ErbB) family, specifically EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4), consists of transmembrane receptor tyrosine kinases that play pivotal roles in regulating cell growth, survival, and differentiation (UniProt P00533, P04626, Q15303). These receptors are activated by the binding of extracellular ligands or through homo- and hetero-dimerization, which triggers intracellular kinase activity and downstream signaling cascades like the MAPK and PI3K/Akt pathways (PubMed: 24513166). Dysregulation of these receptors, often through gene amplification or activating mutations, is a hallmark of several cancers, including breast, non-small cell lung, and gastric cancers (PubMed: 29408103). Therapeutic strategies include the use of monoclonal antibodies and small-molecule tyrosine kinase inhibitors (TKIs) such as afatinib and neratinib, which can target multiple members of the family simultaneously. While some compounds like digoxin have been investigated for indirect modulation of these pathways via Na+/K+-ATPase, they do not exhibit direct binding or interaction with the ErbB receptors (PubMed: 21814163). Clinical management of patients treated with ErbB inhibitors requires monitoring for specific toxicities, most notably dermatological reactions, gastrointestinal distress, and potential cardiotoxicity (StatPearls: ErbB Inhibitors).

Other names

ErbB receptor familyHER familyReceptor tyrosine-protein kinase erbB-1/2/4EGFR/HER2/HER4

Inhibition of the intracellular tyrosine kinase domain of ErbB family receptors (EGFR, HER2, and HER4), preventing autophosphorylation and subsequent activation of downstream signaling pathways like MAPK and PI3K/Akt (PMID: 24513166).