EGFR exon 20 insertion testing identifies a distinct subset of lung adenocarcinomas, accounting for at least 9% of all EGFR-mutated cases and by molecular modeling, are predicted to have potentially different effects on erlotinib binding. Studies show that in contrast to the more classic activating EGFR mutations, these insertions have been associated with de novo resistance to approved EGFR-TKIs (erlotinib and gefitinib). In a recent study, patients with advanced lung adenocarcinoma harboring exon 20 insertions demonstrated no response or partial response following treatment with TK inhibitors. This rare complex mutation (p.H773_V774delinsLM) results in the H773L/V774 mutation compound at the same allele, potentially weakening the inactive state and leading to constitutional activation of EGFR. A recent clinical report suggests this mutation is insensitive to the reversible TKI gefitinib, but can be suppressed by the irreversible TKI osimertinib, leading to sustained disease control (Yang et al., Lung Cancer, 121:1-4, 2018). Exon 20 insertion mutations in EGFR may be associated with clinical trials (https://clinicaltrials.gov/).
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Beau-Faller et al. Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10117 patients: a multicentre observational study by the French ERMETIC-IFCT network. Annals of oncology 25.1 (2014): 126-131.
Vidhula et al. Designing inhibitors for EGFR to improve anti-cancer therapy: An in silico approach. Eur J Biotech and Bioscien, 2014, 2(5):9-14.
Yang et al. Case Report: Osimertinib achieved remarkable and sustained disease control in an advanced non-small-cell lung cancer harboring EGFR H773L/V774M mutation complex. Lung Cancer, 2018, 121:1-4. doi: 10.1016/j.lungcan.2018.04.006. Epub 2018 Apr 5
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