2019
PDK1 Mediates NOTCH1-Mutated Head and Neck Squamous Carcinoma Vulnerability to Therapeutic PI3K/mTOR Inhibition
Sambandam V, Frederick MJ, Shen L, Tong P, Rao X, Peng S, Singh R, Mazumdar T, Huang C, Li Q, Pickering CR, Myers JN, Wang J, Johnson FM. PDK1 Mediates NOTCH1-Mutated Head and Neck Squamous Carcinoma Vulnerability to Therapeutic PI3K/mTOR Inhibition. Clinical Cancer Research 2019, 25: 3329-3340. PMID: 30770351, PMCID: PMC6548600, DOI: 10.1158/1078-0432.ccr-18-3276.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Line, TumorCell ProliferationCRISPR-Cas SystemsDisease Models, AnimalDose-Response Relationship, DrugGene EditingGene ExpressionGene Knockdown TechniquesHumansLoss of Function MutationMicePhosphatidylinositol 3-KinasesProtein Kinase InhibitorsPyruvate Dehydrogenase Acetyl-Transferring KinaseReceptor, Notch1Signal TransductionSquamous Cell Carcinoma of Head and NeckTOR Serine-Threonine KinasesConceptsPI3K/mTOR inhibitorPI3K/mTOR inhibitionPI3K/mTOR pathway inhibitorsMTOR pathway inhibitorsHNSCC cell linesMTOR inhibitorsMTOR inhibitionCell linesPathway inhibitorNeck squamous cell carcinomaDrug-sensitive cell linesClinical response ratePI3K/mTOR pathwaySquamous cell carcinomaBiomarkers of responseOrthotopic xenograft modelCell carcinomaTumor sizeXenograft modelHNSCCSingle agentPDK1 overexpressionResponse rateMolecular vulnerabilitiesPharmacogenomic approach
2017
Integrative Analysis Identifies a Novel AXL–PI3 Kinase–PD-L1 Signaling Axis Associated with Radiation Resistance in Head and Neck Cancer
Skinner HD, Giri U, Yang LP, Kumar M, Liu Y, Story MD, Pickering CR, Byers LA, Williams MD, Wang J, Shen L, Yoo SY, Fan YH, Molkentine DP, Beadle BM, Meyn RE, Myers JN, Heymach JV. Integrative Analysis Identifies a Novel AXL–PI3 Kinase–PD-L1 Signaling Axis Associated with Radiation Resistance in Head and Neck Cancer. Clinical Cancer Research 2017, 23: 2713-2722. PMID: 28476872, PMCID: PMC5457365, DOI: 10.1158/1078-0432.ccr-16-2586.Peer-Reviewed Original ResearchMeSH KeywordsAgedAxl Receptor Tyrosine KinaseB7-H1 AntigenBiomarkers, TumorCarcinoma, Squamous CellCell Line, TumorFemaleGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHumansLymphocytes, Tumor-InfiltratingMaleMiddle AgedPapillomaviridaePhosphatidylinositol 3-KinasesProteomicsProto-Oncogene ProteinsRadiation ToleranceReceptor Protein-Tyrosine KinasesRNA, MessengerSignal TransductionConceptsPD-L1HPV-negative HNSCC tumorsNeck squamous cell carcinomaCell linesHPV-negative HNSCC cell linesLocal failureLocal treatment failurePD-L1 axisPD-L1 expressionTumor-infiltrating lymphocytesSquamous cell carcinomaHuman papilloma virusLow expression groupActivation of AxlHNSCC cell linesClin Cancer ResNegative cell linesTreatment failureCell carcinomaPapilloma virusHNSCC tumorsExpression groupMultivariate analysisMRNA expression analysisPI3-kinase
2012
Lessons learned from next‐generation sequencing in head and neck cancer
Loyo M, Li RJ, Bettegowda C, Pickering CR, Frederick MJ, Myers JN, Agrawal N. Lessons learned from next‐generation sequencing in head and neck cancer. Head & Neck 2012, 35: 454-463. PMID: 22907887, PMCID: PMC3715072, DOI: 10.1002/hed.23100.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellClass I Phosphatidylinositol 3-KinasesCyclin-Dependent Kinase Inhibitor p16DNA Mutational AnalysisGenetic Predisposition to DiseaseHead and Neck NeoplasmsHumansMutationPhosphatidylinositol 3-KinasesProto-Oncogene Proteins p21(ras)Receptor, Notch1Squamous Cell Carcinoma of Head and NeckTumor Suppressor Protein p53ConceptsNeck cancerSquamous cell carcinomaNext-generation sequencingPotential therapeutic interventionsCell carcinomaHuman papillomavirusClinical correlationTherapeutic interventionsCancerCommon mutationsMutation patternsCurrent reviewMutational spectrumNotch1Whole exome captureCellular pathwaysHead