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 approachIdentification of novel diagnostic markers for sinonasal undifferentiated carcinoma
Takahashi Y, Gleber‐Netto F, Bell D, Roberts D, Xie T, Abdelmeguid AS, Pickering C, Myers JN, Hanna EY. Identification of novel diagnostic markers for sinonasal undifferentiated carcinoma. Head & Neck 2019, 41: 2688-2695. PMID: 30932264, DOI: 10.1002/hed.25748.Peer-Reviewed Original ResearchConceptsSinonasal squamous cell carcinomaSinonasal undifferentiated carcinomaUndifferentiated carcinomaDiagnostic markerNew diagnostic molecular markersSquamous cell carcinomaDistinct pathologic entityPotential therapeutic targetNovel diagnostic markerNew diagnostic markersSNSCC patientsNeuroendocrine featuresCell carcinomaHistopathologic markersSquamous lineagePathologic entityUndifferentiated tumorsAggressive cancerTumor specimensTherapeutic targetOncology panelUnsupervised cluster analysisCarcinomaPatientsMarkers
2016
Proteomic Profiling Identifies PTK2/FAK as a Driver of Radioresistance in HPV-negative Head and Neck Cancer
Skinner HD, Giri U, Yang L, Woo SH, Story MD, Pickering CR, Byers LA, Williams MD, El-Naggar A, Wang J, Diao L, Shen L, Fan YH, Molkentine DP, Beadle BM, Meyn RE, Myers JN, Heymach JV. Proteomic Profiling Identifies PTK2/FAK as a Driver of Radioresistance in HPV-negative Head and Neck Cancer. Clinical Cancer Research 2016, 22: 4643-4650. PMID: 27036135, PMCID: PMC5061056, DOI: 10.1158/1078-0432.ccr-15-2785.Peer-Reviewed Original ResearchConceptsHPV-negative HNSCC cell linesHPV-negative HNSCCHNSCC cell linesTargetable biomarkersHuman papillomavirusIndependent cohortCandidate biomarkersPoor disease-free survivalNeck squamous cell carcinomaBiomarker of radioresistanceDisease-free survivalSquamous cell carcinomaDisease-related mortalityMerit further evaluationCell linesFAK inhibitionG2-M arrestFocal adhesion kinaseAdvanced HNSCCWorse DFSCancer Genome AtlasCell carcinomaPharmacologic blockadeCancer subgroupsFAK overexpression
2015
Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients
Osman AA, Neskey DM, Katsonis P, Patel AA, Ward AM, Hsu TK, Hicks SC, McDonald TO, Ow TJ, Alves MO, Pickering CR, Skinner HD, Zhao M, Sturgis EM, Kies MS, El-Naggar A, Perrone F, Licitra L, Bossi P, Kimmel M, Frederick MJ, Lichtarge O, Myers JN. Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients. Cancer Research 2015, 75: 1205-1215. PMID: 25691460, PMCID: PMC4615655, DOI: 10.1158/0008-5472.can-14-2729.Peer-Reviewed Original ResearchConceptsNeck cancer patientsEvolutionary action scoreCancer patientsTP53 mutationsNeck squamous cell carcinomaSquamous cell carcinomaCisplatin-based therapyPlatinum-based therapySubset of headThird of casesNovel scoring systemSurvival benefitProspective evaluationCell carcinomaPlatinum responsePreclinical modelsTreatment selectionAction scoresScoring systemPatientsHNSCCTherapyCoding variantPredictive responseScores
2010
DNA Damage Drives an Activin A–Dependent Induction of Cyclooxygenase-2 in Premalignant Cells and Lesions
Fordyce C, Fessenden T, Pickering C, Jung J, Singla V, Berman H, Tlsty T. DNA Damage Drives an Activin A–Dependent Induction of Cyclooxygenase-2 in Premalignant Cells and Lesions. Cancer Prevention Research 2010, 3: 190-201. PMID: 20028875, PMCID: PMC2954106, DOI: 10.1158/1940-6207.capr-09-0229.Peer-Reviewed Original ResearchMeSH KeywordsActivinsAtaxia Telangiectasia Mutated ProteinsBlotting, WesternBreast NeoplasmsCarcinoma in SituCarcinoma, Ductal, BreastCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p16Cyclooxygenase 2DNA DamageDNA-Binding ProteinsEnzyme-Linked Immunosorbent AssayFemaleGene ExpressionGene Expression ProfilingHumansImmunohistochemistryNeoplasm ProteinsOligonucleotide Array Sequence AnalysisPrecancerous ConditionsProtein Serine-Threonine KinasesRetinoblastoma ProteinReverse Transcriptase Polymerase Chain ReactionSignal TransductionTelomereTelomeric Repeat Binding Protein 2Tumor Suppressor Protein p53Tumor Suppressor ProteinsConceptsCOX-2 expressionCyclooxygenase-2Activin AEpithelial cellsHigh COX-2 expressionPoor clinical outcomeCOX-2 inhibitionCOX-2 inhibitorsTumor-promoting phenotypeSynthesis of prostaglandinsDNA damageDependent inductionVariant human mammary epithelial cellsBreast epithelial cellsHuman mammary epithelial cellsGastrointestinal complicationsSystemic complicationsClinical outcomesDuctal carcinomaCell cycle arrestSitu lesionsChemopreventative agentMammary epithelial cellsCancer metastasisPremalignant cells