2020
Acquired FGFR and FGF Alterations Confer Resistance to Estrogen Receptor (ER) Targeted Therapy in ER+ Metastatic Breast Cancer
Mao P, Cohen O, Kowalski KJ, Kusiel JG, Buendia-Buendia JE, Cuoco MS, Exman P, Wander SA, Waks AG, Nayar U, Chung J, Freeman S, Rozenblatt-Rosen O, Miller VA, Piccioni F, Root DE, Regev A, Winer EP, Lin NU, Wagle N. Acquired FGFR and FGF Alterations Confer Resistance to Estrogen Receptor (ER) Targeted Therapy in ER+ Metastatic Breast Cancer. Clinical Cancer Research 2020, 26: 5974-5989. PMID: 32723837, DOI: 10.1158/1078-0432.ccr-19-3958.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBreast NeoplasmsCell Line, TumorDrug Resistance, NeoplasmExome SequencingFemaleFibroblast Growth Factor 3FulvestrantGene Expression Regulation, NeoplasticHumansMCF-7 CellsMiddle AgedMutationNeoplasm MetastasisPiperazinesProtein Kinase InhibitorsPyridinesReceptor, Fibroblast Growth Factor, Type 1Receptor, Fibroblast Growth Factor, Type 2Receptors, EstrogenXenograft Model Antitumor AssaysConceptsMetastatic breast cancerEstrogen receptorBreast cancerFGFR pathwaySelective estrogen receptor degraderCDK4/6 inhibitor palbociclibBreast cancer cellsMAPK pathwayWhole-exome sequencingResistant cell linesMAPK pathway inhibitorsFulvestrant resistanceInhibitor palbociclibDrug combinationsFGFR inhibitorsTherapyPathway inhibitorMEK inhibitorsConfer resistanceCancer cellsCancerInsulin receptorGenes/pathwaysBiopsyCell lines
2018
Drug Resistance in HER2-Positive Breast Cancer Brain Metastases: Blame the Barrier or the Brain?
Kabraji S, Ni J, Lin NU, Xie S, Winer EP, Zhao JJ. Drug Resistance in HER2-Positive Breast Cancer Brain Metastases: Blame the Barrier or the Brain? Clinical Cancer Research 2018, 24: 1795-1804. PMID: 29437794, PMCID: PMC5899637, DOI: 10.1158/1078-0432.ccr-17-3351.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsAntineoplastic Combined Chemotherapy ProtocolsBlood-Brain BarrierBrain NeoplasmsBreast NeoplasmsClinical Studies as TopicDisease Models, AnimalDrug DevelopmentDrug Evaluation, PreclinicalDrug Resistance, NeoplasmFemaleHumansMiceModels, BiologicalReceptor, ErbB-2Translational Research, BiomedicalTreatment OutcomeXenograft Model Antitumor AssaysConceptsBreast cancer brain metastasesHER2-positive breast cancer brain metastasesTreatment of BCBMHER2-positive breast cancerHER2-targeting drugsInadequate drug penetrationBrain metastasis modelCancer brain metastasesCentral nervous systemClin Cancer ResDrug resistance mechanismsBrain metastasesFirst metastasisEffective therapyCommon siteBreast cancerMetastasis modelPharmacodynamic dataNervous systemTranslational research paradigmDrug penetrationCancer ResDrug sensitivityPatientsDrug development
2016
Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases
Ni J, Ramkissoon SH, Xie S, Goel S, Stover DG, Guo H, Luu V, Marco E, Ramkissoon LA, Kang YJ, Hayashi M, Nguyen QD, Ligon AH, Du R, Claus EB, Alexander BM, Yuan GC, Wang ZC, Iglehart JD, Krop IE, Roberts TM, Winer EP, Lin NU, Ligon KL, Zhao JJ. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nature Medicine 2016, 22: 723-726. PMID: 27270588, PMCID: PMC4938731, DOI: 10.1038/nm.4120.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAminopyridinesAnimalsAntineoplastic AgentsApoptosisBrain NeoplasmsBreast NeoplasmsCarrier ProteinsCaspase 3Cell Cycle ProteinsDNA RepairDrug Resistance, NeoplasmDrug Therapy, CombinationEukaryotic Initiation FactorsEverolimusFemaleGene Expression ProfilingGenomic InstabilityHumansImmunohistochemistryKi-67 AntigenMagnetic Resonance ImagingMechanistic Target of Rapamycin Complex 1MiceMice, SCIDMolecular Targeted TherapyMorpholinesMultiprotein ComplexesNeoplasm TransplantationPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsPhosphorylationReceptor, ErbB-2Remission InductionTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsBreast cancer brain metastasesCancer brain metastasesBrain metastasesHER2-positive breast cancer brain metastasesOrthotopic patient-derived xenograftsPI3KPatient-derived xenograftsDurable remissionsTherapeutic responseMouse modelCombined inhibitionCombination inhibitionMetastasisInhibitionRemissionXenograftsMiceResponse and resistance to BET bromodomain inhibitors in triple-negative breast cancer
Shu S, Lin CY, He HH, Witwicki RM, Tabassum DP, Roberts JM, Janiszewska M, Jin Huh S, Liang Y, Ryan J, Doherty E, Mohammed H, Guo H, Stover DG, Ekram MB, Peluffo G, Brown J, D’Santos C, Krop I, Dillon D, McKeown M, Ott C, Qi J, Ni M, Rao P, Duarte M, Wu S, Chiang C, Anders L, Young R, Winer E, Letai A, Barry W, Carroll J, Long H, Brown M, Shirley Liu X, Meyer C, Bradner J, Polyak K. Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature 2016, 529: 413-417. PMID: 26735014, PMCID: PMC4854653, DOI: 10.1038/nature16508.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAzepinesBinding, CompetitiveCasein Kinase IICell Cycle ProteinsCell Line, TumorCell ProliferationChromatinDrug Resistance, NeoplasmEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticGenome, HumanHumansMediator Complex Subunit 1MiceNuclear ProteinsPhosphorylationPhosphoserineProtein BindingProtein Phosphatase 2Protein Structure, TertiaryProteomicsTranscription FactorsTranscription, GeneticTriazolesTriple Negative Breast NeoplasmsXenograft Model Antitumor Assays
2015
PI3K-p110α mediates resistance to HER2-targeted therapy in HER2+, PTEN-deficient breast cancers
Wang Q, Liu P, Spangle JM, Von T, Roberts TM, Lin NU, Krop IE, Winer EP, Zhao JJ. PI3K-p110α mediates resistance to HER2-targeted therapy in HER2+, PTEN-deficient breast cancers. Oncogene 2015, 35: 3607-3612. PMID: 26500061, PMCID: PMC4846581, DOI: 10.1038/onc.2015.406.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesDrug Resistance, NeoplasmFemaleHumansLapatinibMammary Neoplasms, ExperimentalMice, KnockoutMolecular Targeted TherapyPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseQuinazolinesReceptor, ErbB-2Signal TransductionThiazolesTumor BurdenXenograft Model Antitumor AssaysConceptsBreast tumorsP110β inhibitorsHuman epidermal growth factor receptor 2 (HER2) amplificationP110α inhibitionPTEN lossInhibition of HER2Treatment of HER2Human cancersPI3K pathway activationPTEN-deficient breast cancersGenetic mouse modelsPI3K/Akt signalingPTEN-deficient tumorsPI3K/AktDual HER2Therapeutic regimenHER2 inhibitionPIK3CA mutationsTumor regressionBreast cancerMouse modelXenograft modelHER2Null tumorsHER2 activation