Epidermal growth factor receptor exon 20 mutation (EGFR Exon 20 mutation)

Epidermal growth factor receptor exon 20 mutation refers to a heterogeneous group of in-frame insertion mutations in exon 20 of the EGFR gene, frequently found in non-small cell lung cancer (NSCLC)[1][2][3][4][6]. These alterations occur most commonly between codons 763–775 after the C-helix in the kinase domain, leading to constitutive activation of EGFR signaling and oncogenic transformation[1][2][4][5][6]. Unlike the classical EGFR mutations (exon 19 deletions and exon 21 L858R), exon 20 insertions confer intrinsic resistance to standard EGFR tyrosine kinase inhibitors (e.g., erlotinib, gefitinib, afatinib)[1][2][3][5][6]. However, newer therapies such as mobocertinib, amivantamab, and poziotinib target these specific mutations with increased efficacy in NSCLC[1][8]. The presence of EGFR exon 20 insertions defines a unique molecular subgroup of lung adenocarcinoma, often associated with poor prognosis and limited therapeutic options until recently[1][2][4][6]. Identifying these mutations by genomic profiling is critical for optimal patient management and therapy selection[2][8].

Other names

EGFR Ex20InsEGFR exon 20 insertion mutationsEGFR exon 20 mutationsEGFR exon 20 insertions

Inhibition of EGFR tyrosine kinase activity (mobocertinib, poziotinib, osimertinib, afatinib, erlotinib); Monoclonal antibody binding to EGFR and cMet domains (amivantamab); Prevention of receptor dimerization (cetuximab).