2024
TWIST1 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 mediatorTwist1Transformation to small cell lung cancer is irrespective of EGFR and accelerated by SMAD4-mediated ASCL1 transcription independently of RB1 in non-small cell lung cancer
Ding X, Shi M, Liu D, Cao J, Zhang K, Zhang R, Zhang L, Ai K, Su B, Zhang J. Transformation to small cell lung cancer is irrespective of EGFR and accelerated by SMAD4-mediated ASCL1 transcription independently of RB1 in non-small cell lung cancer. Cell Communication And Signaling 2024, 22: 45. PMID: 38233864, PMCID: PMC10795321, DOI: 10.1186/s12964-023-01260-8.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerSmall cell lung cancerSmall cell lung cancer transformationCell lung cancerTransformation to small cell lung cancerLung cancerEGFR-mutant non-small cell lung cancerMYC inhibitorsNon-small cell lung cancer patientsMechanisms of TKI resistanceEGFR mutation statusResistant lung cancerNon-small cell lung cancer cellsDriver gene statusPhenotype in vitroCancer-related genesPotential functional genesPutative gene functionsCRISPR-Cas 9SCLC transformationTKI resistanceMutation statusNeuroendocrine phenotypeRB1 statusClinical characteristics
2023
Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer
de Miguel F, Gentile C, Feng W, Silva S, Sankar A, Exposito F, Cai W, Melnick M, Robles-Oteiza C, Hinkley M, Tsai J, Hartley A, Wei J, Wurtz A, Li F, Toki M, Rimm D, Homer R, Wilen C, Xiao A, Qi J, Yan Q, Nguyen D, Jänne P, Kadoch C, Politi K. Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer. Cancer Cell 2023, 41: 1516-1534.e9. PMID: 37541244, PMCID: PMC10957226, DOI: 10.1016/j.ccell.2023.07.005.Peer-Reviewed Original ResearchConceptsMammalian SWI/SNF chromatinSWI/SNF chromatinMSWI/SNF complexesGenome-wide localizationGene regulatory signaturesNon-genetic mechanismsEpithelial cell differentiationEGFR-mutant cellsChromatin accessibilitySNF complexCellular programsRegulatory signaturesTKI-resistant lung cancerGene targetsKinase inhibitor resistanceCell differentiationMesenchymal transitionTKI resistancePharmacologic disruptionTyrosine kinase inhibitor resistanceCell proliferationChromatinInhibitor resistanceEGFR-mutant lungKinase inhibitors
2022
MET-induced CD73 restrains STING-mediated immunogenicity of EGFR-mutant lung cancer
Yoshida R, Saigi M, Tani T, Springer B, Shibata H, Kitajima S, Mahadevan N, Campisi M, Kim W, Kobayashi Y, Thai T, Haratani K, Yamamoto Y, Sundararaman S, Knelson E, Vajdi A, Canadas I, Uppaluri R, Paweletz C, Miret J, Lizotte P, Gokhale P, Jänne P, Barbie D. MET-induced CD73 restrains STING-mediated immunogenicity of EGFR-mutant lung cancer. Cancer Research 2022, 82: 4079-4092. PMID: 36066413, PMCID: PMC9627131, DOI: 10.1158/0008-5472.can-22-0770.Peer-Reviewed Original ResearchConceptsEGFR-mutant lung cancerEGFR-TKI-resistant cellsThird-generation EGFR tyrosine kinase inhibitorMET-amplifiedT cell responsesPemetrexed treatmentLung cancerCD8+ T cell immunogenicityEGFR-TKI treatment failureEGFR tyrosine kinase inhibitorsInhibit T cell responsesUpregulation of CD73Humanized mouse modelTyrosine kinase inhibitorsT-cell immunogenicityCell line studiesMET amplificationEGFR-TKIsTKI resistanceTreatment failureCancer immunogenicityCD73 inhibitionT cellsPemetrexedEnhanced immunogenicity
2020
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
2018
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 resistance
2017
Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers
Nilsson MB, Sun H, Diao L, Tong P, Liu D, Li L, Fan Y, Poteete A, Lim SO, Howells K, Haddad V, Gomez D, Tran H, Pena GA, Sequist LV, Yang JC, Wang J, Kim ES, Herbst R, Lee JJ, Hong WK, Wistuba I, Hung MC, Sood AK, Heymach JV. Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers. Science Translational Medicine 2017, 9 PMID: 29118262, PMCID: PMC5870120, DOI: 10.1126/scitranslmed.aao4307.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-AntagonistsAfatinibAMP-Activated Protein Kinase KinasesCarcinoma, Non-Small-Cell LungCell Line, TumorCyclic AMP Response Element-Binding ProteinDrug Resistance, NeoplasmEpinephrineErbB ReceptorsHumansInterleukin-6Lung NeoplasmsMutationNorepinephrineProtein Kinase CProtein Kinase InhibitorsProtein Serine-Threonine KinasesQuinazolinesReceptors, Adrenergic, betaSignal TransductionXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerEGFR inhibitor resistanceΒ-blockersInhibitor resistanceStress hormonesLiver kinase B1Epidermal growth factor receptor tyrosine kinase inhibitor resistanceLower IL-6 concentrationsΒ-blocker useIL-6 concentrationsIL-6 inhibitionCell lung cancerTyrosine kinase inhibitor resistanceEGFR-TKI resistanceInterleukin-6 expressionKinase inhibitor resistanceChronic stress hormonesNSCLC patientsEGFR-TKIIL-6Lung cancerAR activationWorse outcomesNSCLC cellsTKI resistance
2012
BCL6 Interacting Corepressor (BCOR) Functions As Lineage-Specific Tumor Suppressor in B Lymphoid and Myeloid Leukemia
Shojaee S, Geng H, Gearhart M, Bardwell V, Muschen M. BCL6 Interacting Corepressor (BCOR) Functions As Lineage-Specific Tumor Suppressor in B Lymphoid and Myeloid Leukemia. Blood 2012, 120: 1301. DOI: 10.1182/blood.v120.21.1301.1301.Peer-Reviewed Original ResearchB-cell lineageMyeloid leukemiaLeukemia cellsBCR-ABL1B-lymphoidTKI sensitivityBCOR overexpressionLoxP-flanked STOP cassetteCML-like leukemiaProgenitor cellsTumor suppressorBone marrow hematopoietic stemAcute myeloid leukemiaBone marrow progenitor cellsCell lineagesMarrow progenitor cellsTumor suppressor roleMyelodysplastic syndromeMale miceTKI resistanceCML cellsLoxP-flanked allelesFatal diseaseTumor growthLeukemia types
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