2017
TBCRC 036: Window of opportunity clinical trial reveals adaptive kinome reprogramming in single and combination HER2-targeting in breast cancer (BrCa).
Angus S, Stuhlmiller T, Sciaky N, Chen X, Naim R, Tanioka M, Gallagher K, Forero A, Krop I, Thompson A, Murthy R, He X, Perou C, Earp S, Carey L, Johnson G. TBCRC 036: Window of opportunity clinical trial reveals adaptive kinome reprogramming in single and combination HER2-targeting in breast cancer (BrCa). Journal Of Clinical Oncology 2017, 35: 1027-1027. DOI: 10.1200/jco.2017.35.15_suppl.1027.Peer-Reviewed Original ResearchHER2 targetingOpportunity clinical trialAnti-HER2 drugsKinome reprogrammingKinase-targeted therapiesEligible patientsEvaluable ptsTyrosine kinaseImmune compartmentBreast surgeryHER2 inhibitionMultiplexed Inhibitor BeadsClinical trialsBreast cancerImmune responseSpecific receptor tyrosine kinasesBrCa cellsReceptor tyrosine kinasesTumor cellsKinome responsesHER2Distinct expressionKinase SykResistance mechanismsRNA sequencing
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
2013
Beyond trastuzumab and lapatinib: new options for HER2-positive breast cancer .
Zardavas D, Cameron D, Krop I, Piccart M. Beyond trastuzumab and lapatinib: new options for HER2-positive breast cancer . American Society Of Clinical Oncology Educational Book 2013, 33: e2-e11. PMID: 23714441, DOI: 10.1200/edbook_am.2013.33.e2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsChemotherapy, AdjuvantDrug Resistance, NeoplasmFemaleHumansLapatinibMolecular Targeted TherapyNeoadjuvant TherapyProtein Kinase InhibitorsQuinazolinesReceptor, ErbB-2Signal TransductionTrastuzumabTreatment OutcomeConceptsHER2-positive breast cancerDual HER2 blockadeAntibody-drug conjugatesHER2 blockadeBreast cancerMetastatic settingClinical trialsAnti-HER2 resistanceAnti-HER2 agentsLarge randomized trialsHER2-targeted agentsNew treatment optionsAggressive biologic behaviorMajor clinical issueImproved treatment outcomesNew therapeutic avenuesDevelopment of agentsAdjuvant settingNeoadjuvant settingAdvanced diseaseTrastuzumab-DM1Randomized trialsTreatment optionsBiologic rationaleHER2 inhibition