Targeting the EMT transcription factor TWIST1 overcomes resistance to EGFR inhibitors in EGFR-mutant non-small-cell lung cancer
Yochum Z, Cades J, Wang H, Chatterjee S, Simons B, O’Brien J, Khetarpal S, Lemtiri-Chlieh G, Myers K, Huang E, Rudin C, Tran P, Burns T. Targeting the EMT transcription factor TWIST1 overcomes resistance to EGFR inhibitors in EGFR-mutant non-small-cell lung cancer. Oncogene 2018, 38: 656-670. PMID: 30171258, PMCID: PMC6358506, DOI: 10.1038/s41388-018-0482-y.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAmino Acid SubstitutionAniline CompoundsCarcinoma, Non-Small-Cell LungCell Line, TumorDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionErbB ReceptorsHEK293 CellsHumansLung NeoplasmsMutation, MissenseNeoplasm ProteinsNuclear ProteinsPiperazinesProtein Kinase InhibitorsTwist-Related Protein 1ConceptsEGFR tyrosine kinase inhibitorsTyrosine kinase inhibitorsEGFR-TKI resistanceGeneration EGFR tyrosine kinase inhibitorsCell lung cancerEGFR-mutant NSCLCLung cancerTKI resistanceTwist1 overexpressionFirst-generation EGFR tyrosine kinase inhibitorsThird-generation EGFR tyrosine kinase inhibitorEGFR-mutant lung cancerEGFR-mutant NSCLC cellsFirst-line settingLong-term efficacyDe novo resistanceT790M mutationErlotinib-induced apoptosisEpithelial-mesenchymal transition transcription factorsDrivers of EMTDrivers of resistanceEMT transcription factor TWIST1Osimertinib resistanceErlotinib resistanceNovo resistanceTWIST1 is a critical downstream target of the HGF/MET pathway and is required for MET driven acquired resistance in oncogene driven lung cancer
Kumar V, Yochum Z, Devadassan P, Huang E, Miller E, Baruwal R, Rumde P, GaitherDavis A, Stabile L, Burns T. TWIST1 is a critical downstream target of the HGF/MET pathway and is required for MET driven acquired resistance in oncogene driven lung cancer. Oncogene 2024, 43: 1431-1444. PMID: 38485737, PMCID: PMC11068584, DOI: 10.1038/s41388-024-02987-5.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsTKI resistanceMET amplificationEpithelial-mesenchymal transitionMET tyrosine kinase inhibitorsOvercome resistanceTyrosine kinase inhibitor resistanceTargetable oncogenic driversResistance in vitroEffective therapeutic strategySuppression of p27Inhibition of Twist1MET alterationsPDX modelsMET pathwayHGF/MET pathwayOncogenic driversLung cancerLung tumorigenesisKinase inhibitorsP27 expressionTherapeutic strategiesPharmacological inhibitionDownstream mediatorTwist1