Human epidermal growth factor receptor 2 and Epidermal growth factor receptor (HER2 (ERBB2), EGFR (ERBB1))

HER2 (Human epidermal growth factor receptor 2) and EGFR (Epidermal growth factor receptor) are members of the ERBB family of transmembrane receptor tyrosine kinases. HER2 cannot directly bind ligand, but serves as a preferred dimerization partner for other ERBB receptors, including EGFR, facilitating potent signal transduction for cell growth and survival. Both HER2 and EGFR play pivotal roles in normal epithelial cell biology and are frequently dysregulated in various cancers, driving oncogenic signaling and constituting critical targets for anticancer therapy. HER2 overexpression or gene amplification is especially prominent in breast cancer and is associated with aggressive disease, while EGFR is commonly altered by mutation in lung and other solid tumors. Therapeutics targeting these molecules have dramatically improved outcomes in selected populations, although resistance and toxicity remain important clinical challenges.

Other names

ERBB2neuCD340HER-2/neuERBB1HER1

HER2/EGFR blockade: monoclonal antibodies (e.g., trastuzumab, pertuzumab for HER2; cetuximab for EGFR) prevent ligand binding/dimerization. Tyrosine kinase inhibition: small molecule inhibitors (e.g., lapatinib, erlotinib) block ATP-binding site, suppressing kinase activity. Antibody-drug conjugate: targeted cytotoxic payload delivery (e.g., T-DM1 for HER2). Downregulation/externalization: some drugs accelerate receptor endocytosis and degradation.