2017
A phase I study of PF-06647263, a novel EFNA4-ADC, in patients with metastatic triple negative breast cancer.
Garrido-Laguna I, Krop I, Burris H, Hamilton E, Braiteh F, Weise A, Abu-Khalaf M, Zopf C, Lakshminarayanan M, Holland J, Baffa R, Hong D, Hassan R. A phase I study of PF-06647263, a novel EFNA4-ADC, in patients with metastatic triple negative breast cancer. Journal Of Clinical Oncology 2017, 35: 2511-2511. DOI: 10.1200/jco.2017.35.15_suppl.2511.Peer-Reviewed Original ResearchTriple-negative breast cancerAdverse eventsNegative breast cancerExpansion cohortPartial responseBreast cancerMetastatic triple-negative breast cancerAnti-drug antibody developmentCommon adverse eventsDuration of treatmentAnti-tumor activityVivo preclinical studiesQ3w scheduleQW scheduleRECIST responseAdvanced malignanciesMucosal inflammationObjective responseDose escalationTNBC patientsTumor regressionTNBC modelsPreclinical studiesCommon treatmentPK data
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