MEK Inhibitor PD-0325901 Overcomes Resistance to PI3K/mTOR Inhibitor PF-5212384 and Potentiates Antitumor Effects in Human Head and Neck Squamous Cell Carcinoma
Mohan S, Vander Broek R, Shah S, Eytan D, Pierce M, Carlson S, Coupar J, Zhang J, Cheng H, Chen Z, Van Waes C. MEK Inhibitor PD-0325901 Overcomes Resistance to PI3K/mTOR Inhibitor PF-5212384 and Potentiates Antitumor Effects in Human Head and Neck Squamous Cell Carcinoma. Clinical Cancer Research 2015, 21: 3946-3956. PMID: 25977343, PMCID: PMC4558307, DOI: 10.1158/1078-0432.ccr-14-3377.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBenzamidesCarcinoma, Squamous CellCell Line, TumorCell ProliferationCell SurvivalCell Transformation, NeoplasticCytokinesDiphenylamineDisease Models, AnimalDrug Resistance, NeoplasmDrug SynergismGene ExpressionGenes, ReporterHead and Neck NeoplasmsHumansInflammation MediatorsMitogen-Activated Protein Kinase KinasesMorpholinesNF-kappa BPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Kinase InhibitorsSignal TransductionSquamous Cell Carcinoma of Head and NeckTOR Serine-Threonine KinasesTranscription Factor AP-1Transcriptional ActivationTriazinesXenograft Model Antitumor AssaysMEK Inhibitor PD-0325901 Overcomes Resistance to CK2 Inhibitor CX-4945 and Exhibits Anti-Tumor Activity in Head and Neck Cancer
Bian Y, Han J, Kannabiran V, Mohan S, Cheng H, Friedman J, Zhang L, VanWaes C, Chen Z. MEK Inhibitor PD-0325901 Overcomes Resistance to CK2 Inhibitor CX-4945 and Exhibits Anti-Tumor Activity in Head and Neck Cancer. International Journal Of Biological Sciences 2015, 11: 411-422. PMID: 25798061, PMCID: PMC4366640, DOI: 10.7150/ijbs.10745.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzamidesBlotting, WesternCasein Kinase IICell Line, TumorDiphenylamineFemaleFlow CytometryHead and Neck NeoplasmsHumansJNK Mitogen-Activated Protein KinasesMiceMice, Inbred BALB CMice, SCIDNaphthyridinesNF-kappa BPhenazinesProto-Oncogene Proteins c-fosTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsAnti-tumor activityMEK inhibitor PD-0325901PD-901CK2 inhibitor CXModest anti-tumor activityNeck squamous cell carcinomaPD-0325901Cell linesSignificant anti-tumor effectHuman HNSCC cell linesUM-SCC cell linesP-AKT T308Squamous cell carcinomaIL-8 activityFurther clinical investigationAnti-tumor effectsHNSCC cell linesDNA flow cytometryAP-1 pathwayDrug resistance mechanismsExhibit anti-tumor activityResistance mechanismsUM-SCC1Cell carcinomaNeck cancer