Epidermal growth factor receptor exon 20 insertion mutant (EGFR exon 20 insertion mutant)

Epidermal growth factor receptor exon 20 insertion mutants are a diverse group of in-frame insertion mutations in exon 20 of the EGFR gene, which encode the receptor tyrosine kinase critical for cell signaling and proliferation. These mutations result in constitutive activation of the EGFR kinase, leading to persistent downstream signaling that drives oncogenesis, particularly in non-small-cell lung cancer (NSCLC). Exon 20 insertion mutations account for approximately 4–12% of all EGFR mutations in NSCLC, making them the third most common subtype behind exon 19 deletions and exon 21 L858R. Unlike classic EGFR-activating mutations, exon 20 insertions are typically resistant to first- and second-generation EGFR tyrosine kinase inhibitors due to their unique alterations in the kinase domain but are the molecular target of several recently developed small molecule TKIs (e.g., mobocertinib, poziotinib, sunvozertinib, zipalertinib) and the EGFR/c-MET bispecific antibody amivantamab. Detection of these mutations serves both as a therapeutic target and a predictive biomarker for patient selection. The heterogeneity in insertion type and position strongly influences drug sensitivity and clinical outcomes.

Other names

EGFR exon 20 insertionEGFR ex20insEGFR exon 20 insertion mutationEGFR exon 20 mutantEGFR ex20ins mutant

Tyrosine kinase inhibition (by small molecules specifically designed for EGFR exon 20 insertion mutants); EGFR/c-MET bispecific antibody binding and downregulation (in the case of amivantamab)