Epidermal growth factor receptor (EGFR) and Epidermal growth factor receptor variant III (EGFRvIII) (EGFR / EGFRvIII)

The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein that functions as a receptor tyrosine kinase, playing a pivotal role in cell growth, proliferation, and survival signaling pathways such as MAPK and PI3K/Akt (UniProt P00533). EGFRvIII is a common tumor-specific mutation, particularly in glioblastoma, resulting from a genomic deletion of exons 2 through 7 that creates a constitutively active receptor lacking a ligand-binding domain (PubMed: 25855915). While wild-type EGFR is a major therapeutic target in non-small cell lung cancer and colorectal cancer, EGFRvIII presents a unique neoepitope that is absent in normal tissues, making it an attractive target for precision therapies like vaccines and antibody-drug conjugates (PubMed: 30232150). Clinical management of EGFR-driven cancers involves small-molecule tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, though treatment is often complicated by acquired resistance mechanisms like the T790M mutation (StatPearls: NBK531487). Safety profiles for these therapies typically include dermatological and gastrointestinal toxicities due to the physiological role of EGFR in skin and mucosal maintenance (PubMed: 21422441).

Other names

ErbB-1HER1de2-7 EGFREGFR type IIIdelta-EGFRPIG61ERBB

Inhibition of the intracellular tyrosine kinase domain by small molecules, blockade of the extracellular ligand-binding domain by monoclonal antibodies, or immune-mediated targeting of the EGFRvIII-specific neoepitope.