Open AccessGeneration of osimertinib-resistant cells from epidermal growth factor receptor L858R/T790M mutant non-small cell lung carcinoma cell line
Author(s) -
Nalini Devi Verusingam,
YiChen Chen,
Heng Fu Lin,
Chao Yu Liu,
Ming Cheng Lee,
Kai Lü,
Soon Keng Cheong,
Alan Han Kiat Ong,
Shih Hwa Chiou,
MongLien Wang
Publication year - 2020
Publication title -
journal of the chinese medical association
Language(s) - English
Resource type - Journals
eISSN - 1728-7731
pISSN - 1726-4901
DOI - 10.1097/jcma.0000000000000438
Subject(s) - t790m , osimertinib , epidermal growth factor receptor , cancer research , medicine , lung cancer , epithelial–mesenchymal transition , cancer , gefitinib , oncology , erlotinib , metastasis
Lung cancer contributes to high cancer mortality worldwide with 80% of total cases diagnosed as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain serves as a druggable target in NSCLC patients with exon 19 deletion and L858R mutation. However, patients eventually succumbed to resistance to first- and second-generation EGFR-TK inhibitors through activation of T790M mutation. Third-generation EGFR-TKI, Osimertinib exhibits high efficacy in patients with exon 19 deletion/L858R/T790M mutation but they experienced acquired resistance thereafter. Available treatment options in NSCLC patients remains a challenge due to unknown molecular heterogeneity responsible for acquired resistance to EGFR-TKI. In this study, we aim to generate Osimertinib-resistant (OR) cells from H1975 carrying L858R/T790M double mutation which can be used as a model to elucidate mechanism of resistance.