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
2016
Non-malignant respiratory epithelial cells preferentially proliferate from resected non-small cell lung cancer specimens cultured under conditionally reprogrammed conditions
Gao B, Huang C, Kernstine K, Pelekanou V, Kluger Y, Jiang T, Peters-Hall JR, Coquelin M, Girard L, Zhang W, Huffman K, Oliver D, Kinose F, Haura E, Teer JK, Rix U, Le AT, Aisner DL, Varella-Garcia M, Doebele RC, Covington KR, Hampton OA, Doddapaneni HV, Jayaseelan JC, Hu J, Wheeler DA, Shay JW, Rimm DL, Gazdar A, Minna JD. Non-malignant respiratory epithelial cells preferentially proliferate from resected non-small cell lung cancer specimens cultured under conditionally reprogrammed conditions. Oncotarget 2016, 5: 11114-11126. PMID: 28052041, PMCID: PMC5355251, DOI: 10.18632/oncotarget.14366.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAdultAgedAged, 80 and overBase SequenceCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationCells, CulturedCoculture TechniquesDNA Copy Number VariationsDNA Mutational AnalysisEpithelial CellsFemaleGene Expression ProfilingGenetic Predisposition to DiseaseHumansLung NeoplasmsMaleMiddle AgedMutationRespiratory MucosaTumor Cells, CulturedConceptsNon-small cell lung cancerRespiratory epithelial cellsNon-malignant lungCell lung cancerCRC culturesLung cancerEpithelial cellsResected non-small cell lung cancerPrimary lung cancerNon-malignant samplesLung epithelial cellsRho-kinase inhibitorNon-malignant cellsPrimary NSCLCPrimary tumorDiploid patternOriginal tumorTumor specimensTumor tissueTumorsKinase inhibitorsCancerCancer cellsMRNA expression profilesSmall subpopulation
2013
Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel
Jilaveanu LB, Zhao F, Zito CR, Kirkwood JM, Nathanson KL, D'Andrea K, Wilson M, Rimm DL, Flaherty KT, Lee SJ, Kluger HM. Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel. PLOS ONE 2013, 8: e69748. PMID: 23936348, PMCID: PMC3735539, DOI: 10.1371/journal.pone.0069748.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalVEGF-R1FGF-R1Paclitaxel-based therapyVEGF-R1 expressionPre-treatment tumorsPredictive biomarker signaturesMultitarget kinase inhibitorPDGF-RβSitu protein expressionTherapeutic ratioTaxane sensitivityMitogen-activated protein kinase pathwayPatientsVEGF-R3CarboplatinSorafenibVEGF-R2C-kitKinase inhibitorsTherapyProtein expressionPhase IIISorafenib targets
2009
Expression of Sorafenib Targets in Melanoma Patients Treated with Carboplatin, Paclitaxel and Sorafenib
Jilaveanu L, Zito C, Lee SJ, Nathanson KL, Camp RL, Rimm DL, Flaherty KT, Kluger HM. Expression of Sorafenib Targets in Melanoma Patients Treated with Carboplatin, Paclitaxel and Sorafenib. Clinical Cancer Research 2009, 15: 1076-1085. PMID: 19188183, PMCID: PMC4263281, DOI: 10.1158/1078-0432.ccr-08-2280.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBenzenesulfonatesCarboplatinCell Line, TumorDisease-Free SurvivalDrug Delivery SystemsHumansMelanomaMitogen-Activated Protein Kinase 3NiacinamidePaclitaxelPhenylurea CompoundsPyridinesReceptors, Vascular Endothelial Growth FactorSkin NeoplasmsSorafenibTreatment OutcomeConceptsSerine/threonine-protein kinase 1Mitogen-activated protein kinase pathwayHigher ERK1/2Protein kinase 1Fibroblast growth factor receptor 1Protein kinase pathwayReceptor tyrosine kinasesPlatelet-derived growth factor receptor betaGrowth factor receptor betaVEGF-R2 expressionSorafenib targetsB-RAF V600E mutationGrowth factor receptor 1C-RafKinase pathwayVascular endothelial growth factor receptor 2B-RafKinase 1Kinase 1/2Tyrosine kinaseEndothelial growth factor receptor 2Factor receptor 1ERK1/2Kinase inhibitorsMultitarget kinase inhibitor
2007
Assessment of PI3 kinase as a druggable target in melanoma
Aziz S, Pick-Golan E, McCarthy M, Flaherty K, Camp R, Rimm D, Kluger H. Assessment of PI3 kinase as a druggable target in melanoma. Journal Of Clinical Oncology 2007, 25: 8521-8521. DOI: 10.1200/jco.2007.25.18_suppl.8521.Peer-Reviewed Original ResearchPI3-kinaseKinase expressionDrug targetsIntracellular signal transduction pathwaysNumerous cellular functionsSignal transduction pathwaysMajor intracellular signal transduction pathwaysPI3-kinase inhibitorAttractive drug targetValuable drug targetsCellular functionsTransduction pathwaysDifferential expressionBenign neviKinaseDruggable targetsExpression levelsProtein levelsMalignant melanocytesKinase inhibitorsDisease aggressionExpressionMalignant cellsPrimary specimensTarget