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 ResearchMeSH KeywordsAnimalsChromatinChromatin Assembly and DisassemblyDNA HelicasesErbB ReceptorsHumansLung NeoplasmsMammalsMutationNuclear ProteinsProtein Kinase InhibitorsTranscription FactorsConceptsMammalian 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
2020
Drug Sensitivity and Allele Specificity of First-Line Osimertinib Resistance EGFR Mutations
Starrett JH, Guernet AA, Cuomo ME, Poels KE, van Alderwerelt van Rosenburgh IK, Nagelberg A, Farnsworth D, Price KS, Khan H, Ashtekar KD, Gaefele M, Ayeni D, Stewart TF, Kuhlmann A, Kaech S, Unni AM, Homer R, Lockwood WW, Michor F, Goldberg SB, Lemmon MA, Smith PD, Cross D, Politi K. Drug Sensitivity and Allele Specificity of First-Line Osimertinib Resistance EGFR Mutations. Cancer Research 2020, 80: 2017-2030. PMID: 32193290, PMCID: PMC7392201, DOI: 10.1158/0008-5472.can-19-3819.Peer-Reviewed Original ResearchConceptsOsimertinib resistancePreferred first-line therapyThird-generation EGFR tyrosine kinase inhibitorEGFR tyrosine kinase inhibitorsResistance EGFR mutationsFirst-line therapyMutant lung cancerFirst-line osimertinibSubsequent treatment approachesTransgenic mouse modelTyrosine kinase inhibitorsSecondary mutationsErlotinib treatmentLung cancerEGFR mutationsLung adenocarcinomaMouse modelTherapeutic strategiesTherapeutic testingTreatment approachesMutant tumorsResistance mutationsDrug sensitivityDriver mutationsKinase inhibitors
2019
Tumor regression mediated by oncogene withdrawal or erlotinib stimulates infiltration of inflammatory immune cells in EGFR mutant lung tumors
Ayeni D, Miller B, Kuhlmann A, Ho PC, Robles-Oteiza C, Gaefele M, Levy S, de Miguel FJ, Perry C, Guan T, Krystal G, Lockwood W, Zelterman D, Homer R, Liu Z, Kaech S, Politi K. Tumor regression mediated by oncogene withdrawal or erlotinib stimulates infiltration of inflammatory immune cells in EGFR mutant lung tumors. Journal For ImmunoTherapy Of Cancer 2019, 7: 172. PMID: 31291990, PMCID: PMC6617639, DOI: 10.1186/s40425-019-0643-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsErbB ReceptorsErlotinib HydrochlorideLung NeoplasmsMice, TransgenicMutationOncogenesProtein Kinase InhibitorsT-LymphocytesTumor MicroenvironmentConceptsTyrosine kinase inhibitorsEGFR-mutant lung cancerMutant lung cancerTumor regressionErlotinib treatmentLung cancerImmune cellsLung tumorsMouse modelEffects of TKIsGrowth factor receptor tyrosine kinase inhibitorsTumor-infiltrating immune cellsDrug resistanceReceptor tyrosine kinase inhibitorsInflammatory immune cellsInflammatory T cellsEffect of erlotinibEGFR mutant lung tumorsInflammatory cellsImmunological profileT cellsCD40 agonistsImmunostimulatory effectsAlveolar macrophagesErlotinib
2016
Oncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells
Forloni M, Gupta R, Nagarajan A, Sun LS, Dong Y, Pirazzoli V, Toki M, Wurtz A, Melnick MA, Kobayashi S, Homer RJ, Rimm DL, Gettinger SJ, Politi K, Dogra SK, Wajapeyee N. Oncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells. Cell Reports 2016, 16: 457-471. PMID: 27346347, PMCID: PMC4945411, DOI: 10.1016/j.celrep.2016.05.087.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAntineoplastic AgentsBrain NeoplasmsCCAAT-Enhancer-Binding ProteinsCell Line, TumorCpG IslandsDNA MethylationDrug Screening Assays, AntitumorErbB ReceptorsGene Expression Regulation, NeoplasticGene SilencingGlioblastomaHumansLung NeoplasmsMAP Kinase Signaling SystemMixed Function OxygenasesMutationOncogenesProtein Kinase InhibitorsProto-Oncogene ProteinsTranscription, GeneticTumor Suppressor ProteinsUp-RegulationConceptsOncogenic epidermal growth factor receptorMethylation-mediated transcriptional silencingEpidermal growth factor receptorTumor suppressorTranscriptional silencingActive DNA demethylationCancer cellsFamily member 1TET1 knockdownDNA demethylaseDNA demethylationTranscription factorsGrowth factor receptorEctopic expressionCytoplasmic localizationGlioblastoma tumor growthLung cancer cellsTET1 expressionFunctional roleSuppressorFactor receptorMember 1TET1SilencingLung cancer samples