2021
HER2CLIMB-04: Phase 2 open label trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ unresectable locally advanced or metastatic breast cancer with and without brain metastases (trial in progress).
Krop I, Ramos J, Zhang C, Hamilton E. HER2CLIMB-04: Phase 2 open label trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ unresectable locally advanced or metastatic breast cancer with and without brain metastases (trial in progress). Journal Of Clinical Oncology 2021, 39: tps1097-tps1097. DOI: 10.1200/jco.2021.39.15_suppl.tps1097.Peer-Reviewed Original ResearchHuman epidermal growth factor receptor 2Metastatic breast cancerProgression-free survivalDisease control rateDuration of responseBrain metastasesOverall survivalT-DXdEpidermal growth factor receptorRECIST v1.1Metastatic settingTrastuzumab deruxtecanBreast cancerOpen-label phase 2 trialPhase 2 open-label trialSmall molecule tyrosine kinase inhibitorsTopoisomerase I inhibitor payloadTreatment of HER2Epidermal growth factor receptor 2Molecule tyrosine kinase inhibitorsHuman epidermal growth factor receptorActive brain metastasesCombination of tucatinibSolid Tumors v1.1Objective response rate
2015
The Evolving Landscape of HER2 Targeting in Breast Cancer
Moasser MM, Krop IE. The Evolving Landscape of HER2 Targeting in Breast Cancer. JAMA Oncology 2015, 1: 1154. PMID: 26204261, DOI: 10.1001/jamaoncol.2015.2286.Peer-Reviewed Original ResearchConceptsTreatment of HER2Breast cancerImmunologic effectorsHER2 targetingSubstantial single-agent activityHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Value of HER2Lines of therapyGrowth factor receptor 2Single-agent activityLate-stage diseaseStage of diseaseUseful predictive biomarkerHER2 inhibitor lapatinibFactor receptor 2Variety of cytotoxicModest efficacyTrastuzumab resistancePredictive biomarkersCell surface expressionImmunologic activityInhibitor lapatinibReceptor 2Advanced stagePI3K-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