2012
A step towards treating KRAS-mutant NSCLC
Goldberg SB, Schlessinger J, Boyer JL, Herbst RS. A step towards treating KRAS-mutant NSCLC. The Lancet Oncology 2012, 14: 3-5. PMID: 23200176, DOI: 10.1016/s1470-2045(12)70528-4.Peer-Reviewed Original ResearchCombined MEK and VEGFR Inhibition in Orthotopic Human Lung Cancer Models Results in Enhanced Inhibition of Tumor Angiogenesis, Growth, and Metastasis
Takahashi O, Komaki R, Smith PD, Jürgensmeier JM, Ryan A, Bekele BN, Wistuba II, Jacoby JJ, Korshunova MV, Biernacka A, Erez B, Hosho K, Herbst RS, O'Reilly MS. Combined MEK and VEGFR Inhibition in Orthotopic Human Lung Cancer Models Results in Enhanced Inhibition of Tumor Angiogenesis, Growth, and Metastasis. Clinical Cancer Research 2012, 18: 1641-1654. PMID: 22275507, PMCID: PMC3306446, DOI: 10.1158/1078-0432.ccr-11-2324.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBenzimidazolesCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationDisease ProgressionHumansLung NeoplasmsMaleMiceMice, NudeMitogen-Activated Protein KinasesMolecular Targeted TherapyNeovascularization, PathologicPaclitaxelProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)QuinazolinesRas ProteinsReceptors, Vascular Endothelial Growth FactorXenograft Model Antitumor AssaysConceptsSignal-regulated kinase kinaseTumor cell proliferationCell proliferationReceptor tyrosine kinasesKinase kinaseAvailable MEK1/2 inhibitorHuman NSCLC cellsTyrosine kinaseVEGF receptor tyrosine kinasesERK phosphorylationNCI-H441MEK1/2 inhibitorApoptotic effectsAdjacent normal tissuesKinaseNSCLC cellsMEK inhibitionAntiangiogenic effectsSignalingOrthotopic human lung cancer modelAvailable potent inhibitorLung tumor growthPotent inhibitorTumor angiogenesisSelumetinib
2010
Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non-Small Cell Lung Cancer In Vitro and In Vivo
Meng J, Dai B, Fang B, Bekele BN, Bornmann WG, Sun D, Peng Z, Herbst RS, Papadimitrakopoulou V, Minna JD, Peyton M, Roth JA. Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non-Small Cell Lung Cancer In Vitro and In Vivo. PLOS ONE 2010, 5: e14124. PMID: 21124782, PMCID: PMC2993951, DOI: 10.1371/journal.pone.0014124.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBenzimidazolesCarcinoma, Non-Small-Cell LungCell CycleCell Line, TumorCell SurvivalDose-Response Relationship, DrugDrug SynergismFemaleHeterocyclic Compounds, 3-RingHumansLung NeoplasmsMiceMice, Inbred BALB CMice, NudeMitogen-Activated Protein Kinase KinasesProto-Oncogene Proteins c-aktSignal TransductionSurvival AnalysisTumor BurdenXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerCell lung cancerCombination of AZD6244Lung cancer cell linesCombination therapyLung cancerCancer cell linesTumor growthTumor tissueHuman non-small cell lung cancerLung cancer cell growthCell linesHuman lung cancer cell linesSingle drug treatmentSynergistic antitumor activityHuman lung tumorsAnimal survival timeMean animal survival timeCancer cell growthXenograft tumor growthP-AKT expressionLung tumorsDrug treatmentDrug combinationsSurvival time