Epithelial-to-mesenchymal transition (EMT) causing acquired resistance to afatinib in a patient with epidermal growth factor receptor (EGFR )-mutant lung adenocarcinoma

Journal of Thoracic Disease
Mau-Ern PohChee-Shee Chai

Abstract

We report the first case of epithelial-to-mesenchymal transition (EMT) as the cause of acquired resistance to the second-generation EGFR-tyrosine kinase inhibitor (TKI), afatinib in a patient with advanced non-small cell lung cancer (NSCLC) harboring a sensitizing EGFR mutation. Patients with EGFR-mutant NSCLC inevitably develop acquired resistance while on EGFR-TKI treatment. EMT which renders cancer cells more invasive and migratory is one of the mechanisms of acquired resistance to EGFR-TKIs and correlates with a poor prognosis. Possible therapeutic strategies in patients with EMT include blocking M2 muscarinic receptor signalling, targeting EMT with histone deacetylase inhibitors such as entinostat and MEK-inhibitors such as selumetinib, inhibition of microRNAs, immunotherapy and inhibiting fibroblast growth factor receptor-1.

Citations

Jun 7, 2020·International Journal of Molecular Sciences·Milad AshrafizadehGautam Sethi
Apr 27, 2020·Respirology : Official Journal of the Asian Pacific Society of Respirology·Chong-Kin LiamKwun M Fong
Mar 14, 2019·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·J GaoJ-Y Ding
Jan 17, 2021·Pharmaceuticals·Laura Sofia CarvalhoJoão Nuno Moreira
Oct 1, 2019·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Ana C Z GelattiFernando C Santini
Oct 4, 2020·Journal of the Chinese Medical Association : JCMA·Nalini Devi VerusingamMong-Lien Wang
May 5, 2021·Cancer Research·Yuya HagaYosef Yarden

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