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 resistanceA First-in-Class TWIST1 Inhibitor with Activity in Oncogene-Driven Lung Cancer
Yochum Z, Cades J, Mazzacurati L, Neumann N, Khetarpal S, Chatterjee S, Wang H, Attar M, Huang E, Chatley S, Nugent K, Somasundaram A, Engh J, Ewald A, Cho Y, Rudin C, Tran P, Burns T. A First-in-Class TWIST1 Inhibitor with Activity in Oncogene-Driven Lung Cancer. Molecular Cancer Research 2017, 15: 1764-1776. PMID: 28851812, PMCID: PMC5712248, DOI: 10.1158/1541-7786.mcr-17-0298.Peer-Reviewed Original ResearchConceptsOncogene-driven NSCLCTwist1 functionPatient-derived xenograft mouse modelsMarked anti-tumor activityEpithelial-mesenchymal transition transcription factorsNon-small cell lung cancer tumorigenesisSolid tumor malignanciesSingle-cell disseminationLung cancer tumorigenesisNovel therapeutic strategiesXenograft mouse modelCell lung cancer tumorigenesisEffects of harmineAnti-tumor activityConnectivity mapping analysisE2A proteinsNSCLC cellsNSCLC tumorigenesisMutant NSCLCAnalogs/derivativesMouse modelTherapeutic strategiesHarmine treatmentDimer partnerTherapeutic target