EGFR

Class

EGFR tyrosine kinase inhibitor

Epidermal growth factor receptor (EGFR) is a transmembrane protein belonging to the ErbB family of receptor tyrosine kinases. When natural ligands such as epidermal growth factor bind its extracellular domain, EGFR pairs with itself or a related receptor, activating an intracellular kinase domain that triggers signaling cascades controlling cell growth, survival, and division. In many epithelial cancers, EGFR is overactive because of gene mutation, amplification, or overexpression, driving uncontrolled proliferation. Blocking EGFR activity, either with small-molecule tyrosine kinase inhibitors that occupy the kinase's ATP-binding pocket or with antibodies that prevent ligand binding, interrupts this growth signal and can slow or halt tumor progression. Because tumors frequently acquire secondary mutations within the kinase domain that render earlier inhibitors ineffective, successive generations of EGFR-directed agents have been designed to retain potency against these resistant forms, including mutations affecting the gatekeeper residue or exon 20 insertions. EGFR-targeted therapy is most established in non-small cell lung cancer harboring activating mutations, but the target also matters in other epithelial malignancies. Because EGFR is expressed on normal epithelial tissues, particularly skin and gut lining, its inhibition characteristically produces class-related toxicities such as rash and diarrhea, an on-target consequence of blocking a pathway also needed for normal tissue maintenance.