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
2017
Pathway level alterations rather than mutations in single genes predict response to HER2-targeted therapies in the neo-ALTTO trial
Shi W, Jiang T, Nuciforo P, Hatzis C, Holmes E, Harbeck N, Sotiriou C, Peña L, Loi S, Rosa DD, Chia S, Wardley A, Ueno T, Rossari J, Eidtmann H, Armour A, Piccart-Gebhart M, Rimm DL, Baselga J, Pusztai L. Pathway level alterations rather than mutations in single genes predict response to HER2-targeted therapies in the neo-ALTTO trial. Annals Of Oncology 2017, 28: 128-135. PMID: 28177460, PMCID: PMC5834036, DOI: 10.1093/annonc/mdw434.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiopsy, Fine-NeedleBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDNA, NeoplasmExome SequencingFemaleHumansLapatinibMolecular Targeted TherapyMutationProportional Hazards ModelsProtein Kinase InhibitorsQuinazolinesReceptor, ErbB-2RhoA GTP-Binding ProteinTrastuzumabConceptsPathologic complete response
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 samplesRAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors
Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, Combs S, Rimm DL, Giltnane JM, Estrada MV, Sánchez V, Sanders ME, Cook RS, Pilkinton MA, Mallal SA, Wang K, Miller VA, Stephens PJ, Yelensky R, Doimi FD, Gómez H, Ryzhov SV, Darcy PK, Arteaga CL, Balko JM. RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors. Clinical Cancer Research 2016, 22: 1499-1509. PMID: 26515496, PMCID: PMC4794351, DOI: 10.1158/1078-0432.ccr-15-1125.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB7-H1 AntigenBiomarkersCell Line, TumorDisease Models, AnimalDisease ProgressionFemaleGene Expression ProfilingHumansImmunomodulationImmunophenotypingLymphocytes, Tumor-InfiltratingMiceMitogen-Activated Protein KinasesMortalityPhenotypeProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsRas ProteinsSignal TransductionTranscriptomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerTumor-infiltrating lymphocytesImmune checkpoint inhibitorsResidual diseaseNeoadjuvant chemotherapyBreast cancerPD-L1Checkpoint inhibitorsMHC expressionMouse modelPD-1/PD-L1 immune checkpoint inhibitorsPD-L1 immune checkpoint inhibitorsPresence of TILsPD-1/PD-L1Low tumor-infiltrating lymphocytesPD-L1/PDAntitumor immune responseRAS/MAPK activationCell-surface MHC expressionMAPK activationImproved survivalImproved prognosisPredictive biomarkersClinical trialsImmune response
2012
Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells
Zito CR, Jilaveanu LB, Anagnostou V, Rimm D, Bepler G, Maira SM, Hackl W, Camp R, Kluger HM, Chao HH. Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells. PLOS ONE 2012, 7: e31331. PMID: 22355357, PMCID: PMC3280285, DOI: 10.1371/journal.pone.0031331.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic AgentsBlotting, WesternCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCell Line, TumorCell ProliferationClass Ia Phosphatidylinositol 3-KinaseDrug SynergismFemaleFluorescent Antibody TechniqueHumansImmunoenzyme TechniquesLung NeoplasmsMaleMiddle AgedPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktSignal TransductionTissue Array AnalysisTOR Serine-Threonine KinasesConceptsNon-small cell lung cancerNSCLC cell linesDual PI3K/mTOR inhibitorPI3K/AKT/mTOR pathwayPI3K/mTOR inhibitorAKT/mTOR pathwayPI3K inhibitorsNVP-BEZ235MTOR inhibitorsNVP-BKM120MTOR expressionAdvanced stageCell linesMTOR pathwayPI3K subunitsNon-small cell lung cancer cellsK inhibitorsCell lung cancer cellsCell lung cancerSquamous cell carcinomaP85 expressionSynergistic growth inhibitionRegulation of pAktExpression of p85Lung cancer cells
2011
In vitro studies of dasatinib, its targets and predictors of sensitivity
Jilaveanu LB, Zito CR, Aziz SA, Chakraborty A, Davies MA, Camp RL, Rimm DL, Dudek A, Sznol M, Kluger HM. In vitro studies of dasatinib, its targets and predictors of sensitivity. Pigment Cell & Melanoma Research 2011, 24: 386-389. PMID: 21320292, PMCID: PMC4431976, DOI: 10.1111/j.1755-148x.2011.00835.x.Peer-Reviewed Original Research
2010
Vertical Targeting of the Phosphatidylinositol-3 Kinase Pathway as a Strategy for Treating Melanoma
Aziz SA, Jilaveanu LB, Zito C, Camp RL, Rimm DL, Conrad P, Kluger HM. Vertical Targeting of the Phosphatidylinositol-3 Kinase Pathway as a Strategy for Treating Melanoma. Clinical Cancer Research 2010, 16: 6029-6039. PMID: 21169255, PMCID: PMC3058635, DOI: 10.1158/1078-0432.ccr-10-1490.Peer-Reviewed Original Research
2009
C-Raf Is Associated with Disease Progression and Cell Proliferation in a Subset of Melanomas
Jilaveanu LB, Zito CR, Aziz SA, Conrad PJ, Schmitz JC, Sznol M, Camp RL, Rimm DL, Kluger HM. C-Raf Is Associated with Disease Progression and Cell Proliferation in a Subset of Melanomas. Clinical Cancer Research 2009, 15: 5704-5713. PMID: 19737955, PMCID: PMC2763114, DOI: 10.1158/1078-0432.ccr-09-0198.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overBenzenesulfonatesCell Line, TumorCell ProliferationCell SurvivalCohort StudiesDisease ProgressionFemaleGene SilencingHumansIndolesMaleMelanomaMiddle AgedNevusNiacinamidePhenolsPhenylurea CompoundsProtein Kinase InhibitorsProto-Oncogene Proteins c-rafPyridinesRNA, Small InterferingSensitivity and SpecificitySkin NeoplasmsSorafenibYoung AdultConceptsExtracellular signal-regulated kinaseC-RafC-Raf expressionSubset of melanomasPhospho-c-RafSignal-regulated kinaseCell linesProtein kinase inhibitionMitogen-activated protein kinase inhibitionDecreased viabilityDecreased Bcl-2 expressionProtein kinaseCell signalingBcl-2 inhibitionRaf kinaseB-RafMelanoma cell linesPhospho-MEKSpecific siRNAsSitu protein expressionGW5074Major isoformsKinasePhospho-ERKBcl-2 expressionAssociation of constitutively activated hepatocyte growth factor receptor (Met) with resistance to a dual EGFR/Her2 inhibitor in non-small-cell lung cancer cells
Agarwal S, Zerillo C, Kolmakova J, Christensen JG, Harris LN, Rimm DL, DiGiovanna MP, Stern DF. Association of constitutively activated hepatocyte growth factor receptor (Met) with resistance to a dual EGFR/Her2 inhibitor in non-small-cell lung cancer cells. British Journal Of Cancer 2009, 100: 941-949. PMID: 19240716, PMCID: PMC2661782, DOI: 10.1038/sj.bjc.6604937.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorEGFR/HER2 inhibitorsNSCLC cell linesDual EGFR/HER2 inhibitorsGrowth factor receptorMET inhibitorsHER2 inhibitorsUse of EGFREGFR tyrosine kinase inhibitorsCell lung cancer cellsFactor receptorMajority of patientsTreatment of NSCLCCell lung carcinomaTyrosine kinase inhibitorsPotential therapeutic advantagesSubset of tumorsLung cancer cellsCell linesCurrent clinical useReceptor TKTumor cell growthHepatocyte growth factor receptorMaximal growth inhibitionImportant molecular target