Featured Publications
Combinatorial drug screening of mammary cells with induced mesenchymal transformation to identify drug combinations for triple-negative breast cancer
Colavito SA, Platt JT, Held MA, Liu Z, Sokup R, Stern DF. Combinatorial drug screening of mammary cells with induced mesenchymal transformation to identify drug combinations for triple-negative breast cancer. Oncotarget 2019, 10: 4822-4839. PMID: 31448050, PMCID: PMC6690678, DOI: 10.18632/oncotarget.27104.Peer-Reviewed Original ResearchBreast cancerDrug combinationsB-cell lymphoma-2 inhibitorTriple-negative breast cancerEffective treatment strategiesBreast cancer cellsEffective drug combinationsCombination regimenPoor prognosisCombination therapyTreatment optionsTreatment strategiesBCL2 inhibitorsEffective treatmentSelf-renewal capabilityCancerTumor cellsDifferent dosesCancer cellsMammary cellsCheckpoint kinase 1 inhibitorsKinase 1 inhibitorMesenchymal characteristicsMesenchymal transformationUntreated cellsPhosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma
Tworkoski K, Singhal G, Szpakowski S, Zito CI, Bacchiocchi A, Muthusamy V, Bosenberg M, Krauthammer M, Halaban R, Stern DF. Phosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma. Molecular Cancer Research 2011, 9: 801-812. PMID: 21521745, PMCID: PMC3117976, DOI: 10.1158/1541-7786.mcr-10-0512.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCell Line, TumorCell MovementCell ProliferationErbB ReceptorsGene Expression Regulation, NeoplasticGene Knockdown TechniquesHEK293 CellsHumansInfant, NewbornMelanocytesMelanomaPhosphoproteinsPhosphorylationProteomicsReceptor Protein-Tyrosine KinasesReceptor, IGF Type 2RNA, Small InterferingSignal TransductionSkin NeoplasmsSTAT3 Transcription FactorConceptsTherapeutic targetReceptor tyrosine kinasesMelanoma cellsPotential therapeutic targetIdentifies potential therapeutic targetsActive receptor tyrosine kinasesTyrosine kinaseMelanoma cell migrationReceptor expressionBreast cancerAxl knockdownAutocrine circuitTherapeutic interventionsCancer subtypesReceptor tyrosine kinase activationTyrosine kinase activationNovel targetActivated receptorsAxlRNA knockdownMelanomaCell migrationHER3KnockdownIGF1RErbB2 is required for ductal morphogenesis of the mammary gland
Jackson-Fisher AJ, Bellinger G, Ramabhadran R, Morris JK, Lee KF, Stern DF. ErbB2 is required for ductal morphogenesis of the mammary gland. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 17138-17143. PMID: 15569931, PMCID: PMC535384, DOI: 10.1073/pnas.0407057101.Peer-Reviewed Original ResearchConceptsKinase geneNormal mouse mammary gland developmentReceptor kinase geneMammary budMouse mammary gland developmentReceptor tyrosine kinase geneTyrosine kinase geneMammary gland developmentMammary glandImportant normal functionsFunctions of ErbB2Gland developmentDuctal morphogenesisEpithelial treeLobuloalveolar developmentTerminal end budsLuminal spaceBudsGenesErbB2End budsHuman breast cancerAggressive phenotypeBreast cancerNormal function
2021
Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations
Patwardhan GA, Marczyk M, Wali VB, Stern DF, Pusztai L, Hatzis C. Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations. Npj Breast Cancer 2021, 7: 60. PMID: 34040000, PMCID: PMC8154902, DOI: 10.1038/s41523-021-00270-4.Peer-Reviewed Original ResearchHeterogeneous cancer cell populationsCancer cell populationsTriple-negative breast cancerSingle-cell RNA sequencingCell populationsFitness advantageRNA sequencingMDA-MB-231 TNBC cellsDrug resistanceMechanisms of resistanceVitro screening assaysClonal dynamicsTNBC cellsScreening assaysResistant clonesPatterns of resistanceConcomitant treatmentTherapy combinationsBreast cancerClinical studiesTreatment doseTreatment scheduleBarcodesSequencingTreatment
2017
Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer
Wali VB, Langdon CG, Held MA, Platt JT, Patwardhan GA, Safonov A, Aktas B, Pusztai L, Stern DF, Hatzis C. Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer. Cancer Research 2017, 77: 566-578. PMID: 27872098, PMCID: PMC5582957, DOI: 10.1158/0008-5472.can-16-1901.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerTNBC cell linesPairwise drug combinationsClinical translationAggressive diseaseCombination therapyBreast cancerPreclinical proofDrug combinationsCombination treatmentInvestigational drugsSingle agentSensitivity patternCell sensitivityCell linesTherapyApoptotic activityAnticancer activityDownregulated genesMitogenic signalingCrizotinibBlockadeClinicAgentsCancer
2016
PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer
Jeong J, VanHouten JN, Dann P, Kim W, Sullivan C, Yu H, Liotta L, Espina V, Stern DF, Friedman PA, Wysolmerski JJ. PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e282-e290. PMID: 26729871, PMCID: PMC4725473, DOI: 10.1073/pnas.1516138113.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCalciumCarcinogenesisCell Line, TumorCell MembraneCell ProliferationCell SurvivalEndocytosisFemaleFluorescent Antibody TechniqueForkhead Box Protein O1Forkhead Transcription FactorsGene Knockdown TechniquesHSP90 Heat-Shock ProteinsHumansImmunoblottingIntracellular SpaceMammary Neoplasms, AnimalMicePlasma Membrane Calcium-Transporting ATPasesProtein BindingProtein TransportReceptor, ErbB-2Signal TransductionSurvival AnalysisConceptsBreast cancerHigh tumor levelsDegradation of HER2Increases Intracellular CalciumMouse mammary tumor virusBreast cancer cellsMammary tumor virusPMCA2 levelsNeu miceTumor levelsFormation of tumorsHER2 levelsIntracellular calciumTherapeutic targetBreast tumorsHER2Milk calciumExpression correlatesCancerHSP 90Mammary glandCancer cellsTumor virusTumorsCalcium
2014
Overexpression of ERBB4 JM-a CYT-1 and CYT-2 isoforms in transgenic mice reveals isoform-specific roles in mammary gland development and carcinogenesis
Wali VB, Gilmore-Hebert M, Mamillapalli R, Haskins JW, Kurppa KJ, Elenius K, Booth CJ, Stern DF. Overexpression of ERBB4 JM-a CYT-1 and CYT-2 isoforms in transgenic mice reveals isoform-specific roles in mammary gland development and carcinogenesis. Breast Cancer Research 2014, 16: 501. PMID: 25516216, PMCID: PMC4303208, DOI: 10.1186/s13058-014-0501-z.Peer-Reviewed Original ResearchConceptsTerminal end budsBreast cancerRole of ErbB4Transgenic miceCYT-2 isoformsMammary glandKi-67-positive cellsNeoplastic mammary lesionsIsoform-specific rolesBetter therapeutic strategiesMammary gland morphologyEpidermal growth factor receptorMammary terminal end budsMammary ductal morphogenesisErbB4 CYT-2Mammary gland developmentTumor suppressor roleGrowth factor receptorPotential oncogenic functionEarly pregnancyCarcinogenic changesNovel oncogenic propertiesMammary lesionsWhole mount analysisErbB4 expressionSignificance of glioma-associated oncogene homolog 1 (GLI1)expression in claudin-low breast cancer and crosstalk with the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway
Colavito SA, Zou MR, Yan Q, Nguyen DX, Stern DF. Significance of glioma-associated oncogene homolog 1 (GLI1)expression in claudin-low breast cancer and crosstalk with the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway. Breast Cancer Research 2014, 16: 444. PMID: 25252859, PMCID: PMC4303124, DOI: 10.1186/s13058-014-0444-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBreast NeoplasmsCell Line, TumorCell MovementCell ProliferationClaudinsEpithelial-Mesenchymal TransitionFemaleGene ExpressionHeterocyclic Compounds, 2-RingHumansMice, Inbred NODMice, SCIDNeoplasm TransplantationNeoplastic Stem CellsNF-kappa BPromoter Regions, GeneticProtein BindingReceptor Cross-TalkRNA, MessengerSignal TransductionThiazolesTranscription FactorsZinc Finger Protein GLI1ConceptsGlioma-associated oncogene homolog 1Claudin-low cell linesBreast cancer stem cellsCancer stem cellsOncogene homolog 1Gli1 expressionBreast cancerClaudin-low breast cancer subtypeMetastatic breast cancer stem cellsNFκB pathwayCell linesClaudin-low breast cancerActivated B cells (NF-κB) pathwayClaudin-low subtypeHomolog 1Breast cancer subtypesMarkers of EMTB-cell pathwayNFκB subunit p65Stem cellsMesenchymal-like characteristicsPoor prognosisTreatment optionsOrthotopic xenograftsAggressive type
2013
Comparison of HER2 and Phospho-HER2 Expression between Biopsy and Resected Breast Cancer Specimens Using a Quantitative Assessment Method
Bai Y, Cheng H, Bordeaux J, Neumeister V, Kumar S, Rimm DL, Stern DF. Comparison of HER2 and Phospho-HER2 Expression between Biopsy and Resected Breast Cancer Specimens Using a Quantitative Assessment Method. PLOS ONE 2013, 8: e79901. PMID: 24278211, PMCID: PMC3836903, DOI: 10.1371/journal.pone.0079901.Peer-Reviewed Original ResearchConceptsCore needle biopsyBreast cancer casesResection specimensCancer casesHER2/neu overexpressionPrediction of responsePre-analytic variablesNeu overexpressionTumor resectionNeedle biopsyBreast cancerHER2 immunoreactivityRetrospective collectionHER2Drug trastuzumabClinical implicationsHER2 proteinQuantitative immunofluorescenceResectionPHER2Good responseFurther studiesBiopsyTrastuzumabImmunoreactivity
2009
Molecular Classification of Normal and Cancer Mammospheres.
Agarwal S, Camp R, Lannin D, Halligan K, Stern D, Tuck D, Harris L, Rimm D. Molecular Classification of Normal and Cancer Mammospheres. Cancer Research 2009, 69: 501-501. DOI: 10.1158/0008-5472.sabcs-09-501.Peer-Reviewed Original ResearchCancer stem cellsPrimary tumorBreast cancerTumor cellsStem cellsAbsence of CD24Breast cancer specimensHuman breast cancerFine-needle aspirationNormal breast tissueExpression of CD44Tumor tissue samplesPutative stem cell markersCD44-positive cellsKey protein markersEx vivo cultureStem cell markersNovel drug targetsSpecific therapyTreatment successNeedle aspirationCancer specimensMyoepithelial markersBT-20Positive cells
2008
ErbB3 is required for ductal morphogenesis in the mouse mammary gland
Jackson-Fisher AJ, Bellinger G, Breindel JL, Tavassoli FA, Booth CJ, Duong JK, Stern DF. ErbB3 is required for ductal morphogenesis in the mouse mammary gland. Breast Cancer Research 2008, 10: r96. PMID: 19019207, PMCID: PMC2656891, DOI: 10.1186/bcr2198.Peer-Reviewed Original ResearchConceptsTerminal end budsMammary fat padEnd budsMammary budBreast cancerFat padDuctal outgrowthMammary glandHER2/neuHuman breast cancerSmooth muscle actinNormal mammary glandSections of glandsMammary ductal treeMouse mammary gland developmentMammary gland developmentErbB3 functionMouse mammary glandRole of ErbB3Lobuloalveolar developmentEpithelial areaErbB2/HER2/NeuPredictive valueMuscle actinTherapeutic resistanceERBB3/HER3 and ERBB2/HER2 Duet in Mammary Development and Breast Cancer
Stern DF. ERBB3/HER3 and ERBB2/HER2 Duet in Mammary Development and Breast Cancer. Journal Of Mammary Gland Biology And Neoplasia 2008, 13: 215. PMID: 18454306, PMCID: PMC6590701, DOI: 10.1007/s10911-008-9083-7.Peer-Reviewed Original ResearchConceptsBreast cancerCancer etiologyErbB3/HER3Breast cancer etiologyAdditional therapeutic opportunitiesEpidermal growth factor receptor familyGrowth factor receptor familyAkt-dependent pathwayFactor receptor familyMouse modelERBB2 amplificationNeuregulin-2Neuregulin-1Therapeutic opportunitiesTherapeutic toolMammary developmentRegulation of metabolismCancerReceptor familyAggressive propertiesTherapeutic compoundsErbB2ErbB3Eventual developmentEtiologyInfluence of Activation State of ErbB-2 (HER-2) on Response to Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil for Stage II, Node-Positive Breast Cancer: Study 8541 From the Cancer and Leukemia Group B
DiGiovanna MP, Stern DF, Edgerton S, Broadwater G, Dressler LG, Budman DR, Henderson IC, Norton L, Liu ET, Muss HB, Berry DA, Hayes DF, Thor AD. Influence of Activation State of ErbB-2 (HER-2) on Response to Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil for Stage II, Node-Positive Breast Cancer: Study 8541 From the Cancer and Leukemia Group B. Journal Of Clinical Oncology 2008, 26: 2364-2372. PMID: 18390970, PMCID: PMC6589994, DOI: 10.1200/jco.2007.13.6580.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCyclophosphamideDisease-Free SurvivalDose-Response Relationship, DrugDoxorubicinEnzyme ActivationFemaleFluorouracilGene DosageHumansImmunohistochemistryIn Situ Hybridization, FluorescenceLymphatic MetastasisNeoplasm StagingPhosphorylationReceptor, ErbB-2ConceptsLeukemia Group BAdjuvant cyclophosphamideErbB-2Breast cancerGroup BAnthracycline-based adjuvant chemotherapyNode-positive breast cancerAdverse prognostic factorSpecific chemotherapeutic agentsErbB-2 overexpressionActivation stateTumor tissue sectionsAdjuvant chemotherapyCAF doseCALGB 8541Fluorouracil chemotherapyPrognostic factorsAssessable casesFavorable outcomePatientsChemotherapeutic agentsStage IICancerDoseTissue sections
2006
Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4
Jackson-Fisher AJ, Bellinger G, Shum E, Duong JK, Perkins AS, Gassmann M, Muller W, Kent Lloyd KC, Stern DF. Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4. Oncogene 2006, 25: 5664-5672. PMID: 16652155, DOI: 10.1038/sj.onc.1209574.Peer-Reviewed Original ResearchConceptsClinical studiesMammary tumorsMammary glandSimilar latency periodHistology of tumorsLoss of ERBB4Epidermal growth factor receptorTumor suppressorGrowth factor receptorLung metastasesBreast cancerErbb4 allelesMMTV-NeuLatency periodNull miceTumorsReceptor tyrosine kinasesFactor receptorErbB4ErbB familyCancerMiceTyrosine kinaseTissue culture analysisGland
2005
Relationship of Epidermal Growth Factor Receptor Expression to ErbB-2 Signaling Activity and Prognosis in Breast Cancer Patients
DiGiovanna MP, Stern DF, Edgerton SM, Whalen SG, Moore D, Thor AD. Relationship of Epidermal Growth Factor Receptor Expression to ErbB-2 Signaling Activity and Prognosis in Breast Cancer Patients. Journal Of Clinical Oncology 2005, 23: 1152-1160. PMID: 15718311, DOI: 10.1200/jco.2005.09.055.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptor expressionGrowth factor receptor expressionBreast cancer patientsBreast cancerHuman breast cancerFactor receptor expressionErbB-2Cancer patientsReceptor expressionEGFR expressionEarly-stage breast cancerAdverse prognostic valueErbB-2 phosphorylationFirst clinical evidenceInvasive breast cancerPrognosis of patientsPercent of tumorsParaffin tumor sectionsErbB-2 activationErbB-2 overexpressionLigand-dependent mechanismTreatment of tumorsClinical evidencePrognostic valueShorter survivalPhosphorylated/Activated HER2 as a Marker of Clinical Resistance to Single Agent Taxane Chemotherapy for Metastatic Breast Cancer
Modi S, DiGiovanna MP, Lu Z, Moskowitz C, Panageas KS, Van Poznak C, Hudis CA, Norton L, Tan L, Stern DF, Carter D, Seidman AD. Phosphorylated/Activated HER2 as a Marker of Clinical Resistance to Single Agent Taxane Chemotherapy for Metastatic Breast Cancer. Cancer Investigation 2005, 23: 483-487. PMID: 16203655, DOI: 10.1080/07357900500201301.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerSingle-agent taxane therapyTaxane therapyP-HER2Clinical benefitBreast cancerClinical resistanceSingle-agent taxane chemotherapyUnique predictive informationChi-squared analysisTaxane chemotherapyClinical outcomesClinical progressionTaxane monotherapyHER2 statusClinical trialsPhosphorylated HER2Tumor specimensFunctional assessmentHER2TherapyMonoclonal antibodiesImmunohistochemistrySquared analysisProgression
2003
Gene expression profiling of ErbB receptor and ligand-dependent transcription
Amin DN, Perkins AS, Stern DF. Gene expression profiling of ErbB receptor and ligand-dependent transcription. Oncogene 2003, 23: 1428-1438. PMID: 14973552, DOI: 10.1038/sj.onc.1207257.Peer-Reviewed Original ResearchConceptsGene expression profilingExpression profilingInfluences gene transcriptionLigand-dependent transcriptionLigand-independent activationTranscriptional targetsGene transcriptionBreast cancerGene expressionMolecular mechanismsSame cell lineReceptor homodimersOligonucleotide arraysBreast cancer cellsUnidentified targetsErbB receptorsOverexpression of ErbB2GenesCancer cellsCell linesTranscriptionErbB4 receptorsErbB2ErbBClinical outcomesErbBs in mammary development
Stern DF. ErbBs in mammary development. Experimental Cell Research 2003, 284: 89-98. PMID: 12648468, DOI: 10.1016/s0014-4827(02)00103-9.Peer-Reviewed Original ResearchConceptsMammary developmentHuman mammary carcinomaCancer therapyHER2/neuNormal mammary developmentEpidermal growth factor receptorGrowth factor receptorMammary carcinomaBreast cancerErbB2/HER2/NeuRational targetReceptor tyrosine kinasesFactor receptorReceptorsErbB familyTherapyTyrosine kinaseFrequent selectionErbBCarcinomaEtiologyCancerMiceNeu
2000
Activation (tyrosine phosphorylation) of ErbB-2 (HER-2/neu): a study of incidence and correlation with outcome in breast cancer.
Thor AD, Liu S, Edgerton S, Moore D, Kasowitz KM, Benz CC, Stern DF, DiGiovanna MP. Activation (tyrosine phosphorylation) of ErbB-2 (HER-2/neu): a study of incidence and correlation with outcome in breast cancer. Journal Of Clinical Oncology 2000, 18: 3230-9. PMID: 10986055, DOI: 10.1200/jco.2000.18.18.3230.Peer-Reviewed Original ResearchConceptsBreast cancerErbB-2 expressionPrognostic valueErbB-2Node-positive breast cancerNode-positive patientsPositive lymph nodesDisease-specific survivalPrimary breast cancerAdditional prognostic valueInvasive breast cancerNode-positive casesBreast cancer patientsSignificant prognostic valueStudy of incidenceArchival breast cancer samplesErbB-2-positive cellsBreast cancer samplesBreast cancer cellsInvasive breast cancer cellsIdentification of casesLymph nodesPatient groupPoor prognosisCancer patientsTyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases
Stern D. Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases. Breast Cancer Research 2000, 2: 176. PMID: 11250707, PMCID: PMC138772, DOI: 10.1186/bcr51.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBiomarkersBreast NeoplasmsEpidermal Growth FactorErbB ReceptorsFemaleGene AmplificationGene Expression Regulation, DevelopmentalGene Expression Regulation, NeoplasticGenes, erbBHumansProtein-Tyrosine KinasesReceptor, ErbB-2Signal TransductionTranscriptional ActivationTransforming Growth FactorsTrastuzumabConceptsBreast cancerErbB family receptor tyrosine kinasesReceptor tyrosine kinasesHER2/neuTyrosine kinaseEpidermal growth factor receptorGrowth factor receptorClinical trialsSteroid receptorsTherapeutic antibodiesErbB-2Factor receptorReceptorsCancerPhysiological regulatorSignificant subsetFamily membersKinaseOptimal useNeuHormoneTrialsAntibodiesHerceptin