Hypoxia Induces Resistance to EGFR Inhibitors in Lung Cancer Cells via Upregulation of FGFR1 and the MAPK Pathway
Lu Y, Liu Y, Oeck S, Zhang GJ, Schramm A, Glazer PM. Hypoxia Induces Resistance to EGFR Inhibitors in Lung Cancer Cells via Upregulation of FGFR1 and the MAPK Pathway. Cancer Research 2020, 80: 4655-4667. PMID: 32873635, PMCID: PMC7642024, DOI: 10.1158/0008-5472.can-20-1192.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAniline CompoundsAnimalsAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCell HypoxiaCell Line, TumorDrug Resistance, NeoplasmHumansLung NeoplasmsMAP Kinase Signaling SystemMiceProtein Kinase InhibitorsReceptor, Fibroblast Growth Factor, Type 1Up-RegulationXenograft Model Antitumor AssaysConceptsEGFR tyrosine kinase inhibitorsTyrosine kinase inhibitorsEpithelial-mesenchymal transitionNon-small cell lung cancer (NSCLC) cell line H1975Fibroblast growth factor receptor 1 expressionMEK inhibitorsNSCLC cell line H1975EGFR-TKI resistanceEGFR-TKI osimertinibOverexpression of FGFR1Receptor 1 expressionEGFR-TKI sensitivityExpression of FGFR1Lung cancer cellsAttractive therapeutic strategyMAPK pathwayProapoptotic factor BimClinical efficacyConventional therapyDevelopment of resistanceEGFR mutationsSelective small molecule inhibitorsTKI resistanceKnockdown of FGFR1Therapeutic strategies