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 expressionHigh expression of orphan nuclear receptor NR4A1 in a subset of ovarian tumors with worse outcome
Delgado E, Boisen M, Laskey R, Chen R, Song C, Sallit J, Yochum Z, Andersen C, Sikora M, Wagner J, Safe S, Elishaev E, Lee A, Edwards R, Haluska P, Tseng G, Schurdak M, Oesterreich S. High expression of orphan nuclear receptor NR4A1 in a subset of ovarian tumors with worse outcome. Gynecologic Oncology 2016, 141: 348-356. PMID: 26946093, PMCID: PMC5154956, DOI: 10.1016/j.ygyno.2016.02.030.Peer-Reviewed Original ResearchConceptsHigh-grade serous ovarian cancerWorse progression-free survivalProgression-free survivalOvarian cancer cell linesCancer cell linesFree survivalNuclear receptorsOvarian cancerOvarian cancer tissue samplesCell linesGrade serous ovarian cancerExpression of NR4A1Ovarian cancer pathogenesisStage of diseaseTCGA dataNormal ovarian tissuesSerous ovarian cancerCancer tissue samplesNormal ovarian samplesRelevant nuclear receptorsHGSOC cell linesCritical nuclear receptorOverexpression of NR4A1Orphan nuclear receptor NR4A1Ovarian tumors