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
2018
Comprehensive pharmacogenomic profiling of human papillomavirus-positive and -negative squamous cell carcinoma identifies sensitivity to aurora kinase inhibition in KMT2D mutants
Kalu NN, Mazumdar T, Peng S, Tong P, Shen L, Wang J, Banerjee U, Myers JN, Pickering CR, Brunell D, Stephan CC, Johnson FM. Comprehensive pharmacogenomic profiling of human papillomavirus-positive and -negative squamous cell carcinoma identifies sensitivity to aurora kinase inhibition in KMT2D mutants. Cancer Letters 2018, 431: 64-72. PMID: 29807113, DOI: 10.1016/j.canlet.2018.05.029.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisArea Under CurveAurora Kinase ABenzamidesBiomarkersCarcinoma, Squamous CellCell CycleCell LineCell ProliferationDNA-Binding ProteinsDrug Evaluation, PreclinicalFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiceMutationNeoplasm ProteinsNeoplasm TransplantationPapillomaviridaePapillomavirus InfectionsPharmacogeneticsPyrazolesUterine Cervical NeoplasmsConceptsAurora kinase inhibitorsDrug sensitivityWild-type cellsPolo-like kinasesInhibitor-induced apoptosisHigh-throughput drug screensNeck squamous cell carcinomaKinase inhibitorsHPV-negative cell linesSquamous cell carcinomaEffective drug classAurora kinase inhibitionG2-M arrestAurora kinasesHistone deacetylaseAurora inhibitorsCervical cancerTumor sizeCell carcinomaHuman papillomavirusCancer DatabaseDrug classesPharmacogenomic profilingXenograft modelM arrest