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
2021
SRC family kinase (SFK) inhibitor dasatinib improves the antitumor activity of anti-PD-1 in NSCLC models by inhibiting Treg cell conversion and proliferation
Redin E, Garmendia I, Lozano T, Serrano D, Senent Y, Redrado M, Villalba M, De Andrea CE, Exposito F, Ajona D, Ortiz-Espinosa S, Remirez A, Bertolo C, Sainz C, Garcia-Pedrero J, Pio R, Lasarte J, Agorreta J, Montuenga LM, Calvo A. SRC family kinase (SFK) inhibitor dasatinib improves the antitumor activity of anti-PD-1 in NSCLC models by inhibiting Treg cell conversion and proliferation. Journal For ImmunoTherapy Of Cancer 2021, 9: e001496. PMID: 33658304, PMCID: PMC7931761, DOI: 10.1136/jitc-2020-001496.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationDasatinibDrug Resistance, NeoplasmFemaleHumansImmune Checkpoint InhibitorsLung NeoplasmsLymphocytes, Tumor-InfiltratingMiceMice, 129 StrainPhenotypeProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsProto-Oncogene Proteins c-yesSignal TransductionT-Lymphocytes, RegulatoryTumor MicroenvironmentConceptsNon-small cell lung cancerNumber of TregsMultiplex immunofluorescenceAntiprogrammed cell death 1 (PD-1) antibodySrc family kinase (SFK) inhibitor dasatinibTumor growthInhibitor dasatinibCell death 1 antibodyYES1 expressionDeath-1 antibodyImmune cytotoxic activityPD-1 treatmentPD-1/Treg cell conversionUse of dasatinibVivo depletion experimentsAntitumor activityImmune checkpoint inhibitorsOutcomes of patientsProtein expressionCohort of patientsManagement of patientsCell lung cancerRelevant mouse modelVivo drug testing