Epidermal growth factor receptor (EGFR) exon 20 insertion (EGFR ex20ins)

The Epidermal growth factor receptor (EGFR) exon 20 insertion is a specific oncogenic driver mutation characterized by the insertion of amino acids into the C-helix or the loop following the C-helix of the kinase domain (Vyse & Huang, 2019, Signal Transduction and Targeted Therapy). These mutations result in a constitutively active kinase that drives cell proliferation and survival through the MAPK and PI3K/AKT pathways, primarily in non-small cell lung cancer (NSCLC) (Remon et al., 2020, Journal of Thoracic Oncology). Unlike common EGFR mutations, exon 20 insertions create a restricted binding pocket that limits the efficacy of first- and second-generation tyrosine kinase inhibitors (TKIs) (Robichaux et al., 2018, Nature Medicine). Therapeutic interventions now include bispecific antibodies like amivantamab, which targets the extracellular domain, and specialized small-molecule TKIs like mobocertinib and sunvozertinib (FDA.gov, 2021; Wang et al., 2022, Lancet Oncology). Clinical identification of these variants typically requires next-generation sequencing (NGS), as standard PCR assays may fail to detect the high diversity of insertion sequences (Bauml et al., 2021, JAMA Oncology).

Other names

EGFR exon 20 insertion mutationERBB1 exon 20 insertionHER1 exon 20 insertionEGFR ex20ins

Targeted inhibition of the mutated EGFR tyrosine kinase domain or bispecific antibody binding to the extracellular domain to inhibit signaling and induce receptor degradation.