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 resistanceTMEM16A/ANO1 Inhibits Apoptosis Via Downregulation of Bim Expression
Godse N, Khan N, Yochum Z, Gomez-Casal R, Kemp C, Shiwarski D, Seethala R, Kulich S, Seshadri M, Burns T, Duvvuri U. TMEM16A/ANO1 Inhibits Apoptosis Via Downregulation of Bim Expression. Clinical Cancer Research 2017, 23: 7324-7332. PMID: 28899969, PMCID: PMC5898434, DOI: 10.1158/1078-0432.ccr-17-1561.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaGreater tumor sizeSquamous cell carcinomaCalcium-activated chloride channelClin Cancer ResERK 1/2 activityVariety of cancersTMEM16A overexpressionCisplatin-resistant phenotypeAggressive diseaseTumor sizeCell carcinomaHuman HNSCCLaryngeal cancerHNSCC samplesTMEM16A expressionChemoradiation failureAnti-apoptotic roleOverexpression rateTranslational investigationsMalignant cellsPotential biomarkersSimilar outcomesCancer ResProtein expression