Lu Y, Liu Y, Oeck S, et al. - The key barrier to the clinical efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is resistance development, and hypoxia is a key factor in solid tumors related to resistance to conventional treatment, so researchers demonstrated that resistance to the EGFR TKI osimertinib (AZD9291) is promoted by long-term moderate hypoxia in the NSCLC cell line H1975, which harbors two EGFR mutations including T790M. This finding is consistent with their previous studies. Hypoxia-induced resistance was found to be related to occurrence of epithelial-mesenchymal transition (EMT) coordinated by raised expression of ZEB-1, an EMT activator. Upregulated expression of fibroblast growth factor receptor 1 (FGFR1) by hypoxia was shown to be mediated via the MAPK pathway and reduced induction of the pro-apoptotic factor BIM. Based on these findings, experts concluded hypoxia is a driving force for acquired resistance to EGFR TKIs via increased expression of FGFR1. An attractive treatment approach for NSCLC may be afforded by the combination of EGFR TKI and FGFR1 or MEK inhibitors.