Figure 1.

The EGFR protein structure and corresponding gene exons. Exons 1–16 encode extracellular domains I-IV (orange) which can form the ligand interaction conformation. Exons 17–18 encode the transmembrane domain (blue) for connecting extracellular domains and intracellular domains. Exons 19–24 encode tyrosine kinase domain. Exon 19 deletion and exon 21 L858R mutation are original mutations that cause constant activation of tyrosine kinase activity in non-small cell lung carcinoma. Exon 20 T790M is the dominant secondary mutation acquired in response to the 1st and 2nd generation TKIs, while exon 20 C797s mutation is the secondary mutation acquired in response to the 3rd generation TKI osimertinib. Exon 25–28 encode C-terminal phosphorylation domain which mediates the interactions between the receptor and downstream substrates upon receptor activation. Abbreviations: EGF, epidermal growth factor; ECD, extracellular domain; TM, transmembrane; ICD, intracellular domain; TK, tyrosine kinase; RD, regulatory/phosphorylation domain