Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor and a member of the ERB family of proteins that plays a role in cell division, cell differentiation, and migration.1,2,3

  • Ligand binding induces EGFR dimerization and activation (there are 7 known ligands4)
    • Epidermal growth factor (EGF)
    • Transforming growth factor-alpha (TGFA)
    • Heparin-binding EGF-like growth factor (HBEGF)
    • Betacellulin (BTC)
    • Amphiregulin (AREG)
    • Epiregulin (EREG)
    • Epigen (EPGN)
  • EGFR is a regulator of normal cellular growth in tissues of epithelial origin4
  • Activation of the EGFR signaling pathway has many effects including increased proliferation and angiogenesis, and decreased apoptosis.5


In cancer, the EGFR gene is often amplified, overexpressed, or mutated, resulting in abnormal signaling and malignant

cellular behaviors; this dysregulation has a causal role in the development and maintenance of certain human


  • EGFR overexpression has been shown in a variety of human epithelial tumors
    • Overexpression is often a consequence of gene amplification, containing gene rearrangements
    • Most common extracellular domain mutation is the EGFRvIII (variant III) deletion
      • Aberrant EGFRvIII signaling has been shown to be important in driving tumor progression and often correlates with poor prognosis

Oncogenic Expression

EGFR is expressed or highly expressed in a variety of human tumors including non-small cell lung cancer (NSCLC), breast, head and neck, gastric, colorectal, esophageal, prostate, bladder, renal, pancreatic, and ovarian cancers.


EGFR mutations typically occur in exons 18–21, are established driver mutations in NSCLC, and are observed in ~10-30% of NSCLC patients.7,8

  • Patients with classical EGFR mutations (deletions in exon 19, L858R in exon 21), most commonly found in Asian patients and those with adenocarcinoma histology, nonsmokers and women, show marked improvements in clinical outcomes when treated with first-, second- or third-generation tyrosine kinase inhibitors (TKIs).6,7
  • Patients with atypical EGFR mutations show heterogeneous and reduced responses to EGFR inhibitors and there are no clear established guidelines for EGFR TKI treatment for patients with atypical EGFR mutations, often resulting in patients receiving chemotherapy.7

Somatic EGFR mutations have been favored over clinical and pathological factors for deciding which patients should receive treatment with tyrosine kinase inhibitors.6

Targeting mutated EGFR is one of the most successful examples of targeted therapy in cancer.8

  1. Mendelsohn J, Baselga J. Epidermal growth factor receptor targeting in cancer. Semin Oncol. 2006;33(4):369-385.
  2. Klein P, Mattoon D, Lemmon MA, Schlessinger J. A structure-based model for ligand binding and dimerization of EGF receptors. Proc Natl Acad Sci USA. 2004;101(4):929-934.
  3. Gan HK, Cvrljevic AN, Johns TG. The epidermal growth factor receptor variant III (EGFRvIII): where the wild things are altered. FEBS J. 2013;280(21):5350-5370.
  4. Singh B, et al. EGF receptor ligands: recent advances [version 1; referees: 3 approved]. F1000Research. 2016;5(F1000 Faculty Rev):2270.
  5. Arteaga, CL. Epidermal Growth Factor Receptor Dependence in Human Tumors: More Than Just Expression? The Oncologist. 2002;7(suppl 4):31-39.
  6. Linardou H, Dahabreh IJ, Bafaloukos D, Kosmidis P, Murray S. Somatic EGFR mutations and efficacy of tyrosine kinase inhibitors in NSCLC. Nature reviews Clinical oncology. 2009 Jun;6(6):352-66.
  7. Robichaux JP, Le X, Vijayan RS, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature. 2021 Sep;597(7878):732-7. 
  8. Stewart EL, Tan SZ, Liu G, Tsao MS. Known and putative mechanisms of resistance to EGFR targeted therapies