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
2009
A phase II study of oral enzastaurin in patients with metastatic breast cancer previously treated with an anthracycline and a taxane containing regimen
Mina L, Krop I, Zon RT, Isakoff SJ, Schneider CJ, Yu M, Johnson C, Vaughn LG, Wang Y, Hristova-Kazmierski M, Shonukan OO, Sledge GW, Miller KD. A phase II study of oral enzastaurin in patients with metastatic breast cancer previously treated with an anthracycline and a taxane containing regimen. Investigational New Drugs 2009, 27: 565. PMID: 19214387, DOI: 10.1007/s10637-009-9220-1.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerPhase II studyPI3K/AktII studyBreast cancerGrade 3/4 hematologic toxicitiesMedian progression-free survivalGrade 3 nonhematologic toxicityHuman epidermal growth factor 2Epidermal growth factor 2Prior trastuzumab therapyCycles of therapySolid Tumors criteriaProgression-free survivalResponse Evaluation CriteriaBreast cancer pathogenesisSerine-threonine kinase inhibitorMBC progressionOral enzastaurinPrior anthracyclineEligible patientsHematologic toxicityMeasurable diseaseNonhematologic toxicityPrior regimens