2022
Combined TRIP13 and Aurora Kinase Inhibition Induces Apoptosis in Human Papillomavirus-Driven Cancers.
Ghosh S, Mazumdar T, Xu W, Powell RT, Stephan C, Shen L, Shah PA, Pickering CR, Myers JN, Wang J, Frederick MJ, Johnson FM. Combined TRIP13 and Aurora Kinase Inhibition Induces Apoptosis in Human Papillomavirus-Driven Cancers. Clinical Cancer Research 2022, 28: 4479-4493. PMID: 35972731, PMCID: PMC9588713, DOI: 10.1158/1078-0432.ccr-22-1627.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAlphapapillomavirusApoptosisATPases Associated with Diverse Cellular ActivitiesAurora KinasesCell Cycle ProteinsFemaleHumansOncogene Proteins, ViralPapillomaviridaePapillomavirus E7 ProteinsPapillomavirus InfectionsRetinoblastoma ProteinUterine Cervical NeoplasmsConceptsHPV-positive cancer cellsInhibition-induced apoptosisAurora kinase inhibitorsAurora kinase inhibitionCancer cellsKinase inhibitionAbsence of RbViral oncoprotein E7Kinase inhibitorsMitotic exitAAA-ATPaseProtein degradationRb functionMechanisms of sensitivityPathway componentsTRIP13MAD2L1Extensive apoptosisCancer cell linesSquamous cancer cell linesApoptosisCell linesRetinoblastoma expressionBUB1BProtein expression correlatesp16 Represses DNA Damage Repair via a Novel Ubiquitin-Dependent Signaling Cascade
Molkentine DP, Molkentine JM, Bridges KA, Valdecanas DR, Dhawan A, Bahri R, Hefner AJ, Kumar M, Yang L, Abdelhakiem M, Pifer PM, Sandulache V, Sheth A, Beadle BM, Thames HD, Mason KA, Pickering CR, Meyn RE, Skinner HD. p16 Represses DNA Damage Repair via a Novel Ubiquitin-Dependent Signaling Cascade. Cancer Research 2022, 82: 916-928. PMID: 34965932, PMCID: PMC9136619, DOI: 10.1158/0008-5472.can-21-2101.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellCarrier ProteinsCyclin-Dependent Kinase Inhibitor p16DNA DamageDNA, ViralHead and Neck NeoplasmsHumansPapillomaviridaePapillomavirus InfectionsSignal TransductionSquamous Cell Carcinoma of Head and NeckTumor Suppressor ProteinsUbiquitinUbiquitin-Protein LigasesUbiquitin-Specific Peptidase 7ConceptsUbiquitin-specific protease 7DNA damage repairDamage repairHPV-positive tumorsTranscription factor Sp1Human papillomavirusFactor Sp1Neck squamous cell carcinoma cellsDNA-damaging therapiesRenders cellsHomologous recombinationSignaling cascadesHPV-negative diseaseSquamous cell carcinoma cellsHPV-negative counterpartsHPV-positive diseaseSquamous cell carcinomaUSP7 inhibitorsDNA damageHPV-negative HNSCCFunctional roleDegradation pathwayHPV positivityPathwayUndiscovered pathways
2021
Biology of the Radio- and Chemo-Responsiveness in HPV Malignancies
Spiotto MT, Taniguchi CM, Klopp AH, Colbert LE, Lin SH, Wang L, Frederick MJ, Osman AA, Pickering CR, Frank SJ. Biology of the Radio- and Chemo-Responsiveness in HPV Malignancies. Seminars In Radiation Oncology 2021, 31: 274-285. PMID: 34455983, PMCID: PMC8689584, DOI: 10.1016/j.semradonc.2021.02.009.Peer-Reviewed Original ResearchConceptsHPV-positive cancersPotential biological mechanismsHPV-positive cancer cellsHPV-negative cancersCancer cellsImproved clinical outcomesCancer stem cell subpopulationMultiple anatomic sitesHPV-negative cellsG2/M arrestBiological mechanismsHPV MalignanciesLocoregional controlOverall survivalClinical outcomesPreclinical observationsAnatomic sitesHypoxic tumor microenvironmentStem cell subpopulationCancerTumor microenvironmentCell subpopulationsRadiosensitive phaseImpaired DNA damage responseOxidative stress
2020
Identifying predictors of HPV‐related head and neck squamous cell carcinoma progression and survival through patient‐derived models
Facompre ND, Rajagopalan P, Sahu V, Pearson AT, Montone KT, James CD, Gleber‐Netto F, Weinstein GS, Jalaly J, Lin A, Rustgi AK, Nakagawa H, Califano JA, Pickering CR, White EA, Windle BE, Morgan IM, Cohen RB, Gimotty PA, Basu D. Identifying predictors of HPV‐related head and neck squamous cell carcinoma progression and survival through patient‐derived models. International Journal Of Cancer 2020, 147: 3236-3249. PMID: 32478869, PMCID: PMC7554059, DOI: 10.1002/ijc.33125.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsClass I Phosphatidylinositol 3-KinasesErbB ReceptorsExome SequencingFemaleGenetic Association StudiesHead and Neck NeoplasmsHumansMaleMiceMutationNeoplasm TransplantationPapillomaviridaePapillomavirus E7 ProteinsPapillomavirus InfectionsPatient-Specific ModelingPrognosisSquamous Cell Carcinoma of Head and NeckSurvival AnalysisTNF Receptor-Associated Factor 3ConceptsPatient-derived xenograftsTumor mutational burdenPreclinical modelsMutational burdenHuman papilloma virus-related headHigh tumor mutational burdenNeck squamous cell carcinomaSquamous cell carcinoma progressionNeck squamous cell carcinoma progressionInadequate preclinical modelsSquamous cell carcinomaDisease recurrence riskPatient-derived modelsLow engraftment rateWhole-exome sequencingViral oncogene functionPrognostic alterationsLocal progressionHPV- patientsCancer Genome AtlasCell carcinomaHPV casesPIK3CA mutationsEngraftment rateLethal outcome
2019
Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma
Haddad RI, Massarelli E, Lee JJ, Lin HY, Hutcheson K, Lewis J, Garden AS, Blumenschein GR, William WN, Pharaon RR, Tishler RB, Glisson BS, Pickering C, Gold KA, Johnson FM, Rabinowits G, Ginsberg LE, Williams MD, Myers J, Kies MS, Papadimitrakopoulou V. Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma. Annals Of Oncology 2019, 30: 471-477. PMID: 30596812, PMCID: PMC7360148, DOI: 10.1093/annonc/mdy549.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCetuximabCisplatinDocetaxelFemaleFluorouracilHumansInduction ChemotherapyMaleMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPaclitaxelPapillomaviridaePapillomavirus InfectionsProgression-Free SurvivalSquamous Cell Carcinoma of Head and NeckConceptsProgression-free survivalSquamous cell carcinomaHigh-risk groupNeck squamous cell carcinomaPrimary end pointInduction chemotherapyLocal therapyCell carcinomaC-TPFAdvanced headT stageHistorical controlsEnd pointPhase II clinical trialHuman papillomavirus (HPV) statusLow-risk groupEligible patientsMedian followWeekly paclitaxelLocoregional treatmentT3-4P16 statusClinical trialsRisk groupsHPV
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
2017
Distinct pattern of TP53 mutations in human immunodeficiency virus–related head and neck squamous cell carcinoma
Gleber‐Netto F, Zhao M, Trivedi S, Wang J, Jasser S, McDowell C, Kadara H, Zhang J, Wang J, William WN, Lee JJ, Nguyen ML, Pai SI, Walline HM, Shin DM, Ferris RL, Carey TE, Myers JN, Pickering CR, Consortium F. Distinct pattern of TP53 mutations in human immunodeficiency virus–related head and neck squamous cell carcinoma. Cancer 2017, 124: 84-94. PMID: 29053175, PMCID: PMC5785080, DOI: 10.1002/cncr.31063.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCadherinsCarcinoma, Squamous CellCase-Control StudiesCaspase 8Class I Phosphatidylinositol 3-KinasesCyclin D1Cyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18ErbB ReceptorsF-Box-WD Repeat-Containing Protein 7FemaleHead and Neck NeoplasmsHistone MethyltransferasesHistone-Lysine N-MethyltransferaseHIV InfectionsHLA-A AntigensHumansIn Situ HybridizationIntracellular Signaling Peptides and ProteinsKelch-Like ECH-Associated Protein 1LIM Domain ProteinsMaleMiddle AgedNF-E2-Related Factor 2Nuclear ProteinsPapillomaviridaePapillomavirus InfectionsProtein Serine-Threonine KinasesProto-Oncogene Proteins p21(ras)Receptor, Notch1Receptor, Notch2Receptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaSquamous Cell Carcinoma of Head and NeckTranscription FactorsTumor Suppressor Protein p53Tumor Suppressor ProteinsConceptsHuman immunodeficiency virus-infected individualsHuman immunodeficiency virus (HIV) infectionNeck squamous cell carcinomaHuman papillomavirus (HPV) statusImmunodeficiency virus infectionVirus-infected individualsSquamous cell carcinomaSample of HIVTP53 mutation frequencyHNSCC patientsCell carcinomaHistopathological differencesPolymerase chain reactionIon Reporter softwareP16 immunostainingDistinct biologyVirus infectionHigh incidenceHIVHNSCCMultiplex polymerase chain reactionDistinct patternsHIV virusTumor samplesTP53 geneIntegrative 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
2015
Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas
Wang Y, Springer S, Mulvey CL, Silliman N, Schaefer J, Sausen M, James N, Rettig EM, Guo T, Pickering CR, Bishop JA, Chung CH, Califano JA, Eisele DW, Fakhry C, Gourin CG, Ha PK, Kang H, Kiess A, Koch WM, Myers JN, Quon H, Richmon JD, Sidransky D, Tufano RP, Westra WH, Bettegowda C, Diaz LA, Papadopoulos N, Kinzler KW, Vogelstein B, Agrawal N. Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Science Translational Medicine 2015, 7: 293ra104. PMID: 26109104, PMCID: PMC4587492, DOI: 10.1126/scitranslmed.aaa8507.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaOral cavity cancerSquamous cell carcinomaTumor DNACell carcinomaOral cavityDetection of HNSCCLate-stage diseaseFraction of patientsPlasma of patientsTumor-specific DNASomatic mutationsHNSCC patientsPatientsValuable biomarkerClinical diagnosisHuman papillomavirus genesCancerSalivaCarcinomaRecurrenceBiomarkersHPVOropharynxHNSCC
2014
Characterization of HPV and host genome interactions in primary head and neck cancers
Parfenov M, Pedamallu CS, Gehlenborg N, Freeman SS, Danilova L, Bristow CA, Lee S, Hadjipanayis AG, Ivanova EV, Wilkerson MD, Protopopov A, Yang L, Seth S, Song X, Tang J, Ren X, Zhang J, Pantazi A, Santoso N, Xu AW, Mahadeshwar H, Wheeler DA, Haddad RI, Jung J, Ojesina AI, Issaeva N, Yarbrough WG, Hayes DN, Grandis JR, El-Naggar AK, Meyerson M, Park PJ, Chin L, Seidman JG, Hammerman PS, Kucherlapati R, Ally A, Balasundaram M, Birol I, Bowlby R, Butterfield Y, Carlsen R, Cheng D, Chu A, Dhalla N, Guin R, Holt R, Jones S, Lee D, Li H, Marra M, Mayo M, Moore R, Mungall A, Robertson A, Schein J, Sipahimalani P, Tam A, Thiessen N, Wong T, Protopopov A, Santoso N, Lee S, Parfenov M, Zhang J, Mahadeshwar H, Tang J, Ren X, Seth S, Haseley P, Zeng D, Yang L, Xu A, Song X, Pantazi A, Bristow C, Hadjipanayis A, Seidman J, Chin L, Park P, Kucherlapati R, Akbani R, Casasent T, Liu W, Lu Y, Mills G, Motter T, Weinstein J, Diao L, Wang J, Fan Y, Liu J, Wang K, Auman J, Balu S, Bodenheimer T, Buda E, Hayes D, Hoadley K, Hoyle A, Jefferys S, Jones C, Kimes P, Marron J, Meng S, Mieczkowski P, Mose L, Parker J, Perou C, Prins J, Roach J, Shi Y, Simons J, Singh D, Soloway M, Tan D, Veluvolu U, Walter V, Waring S, Wilkerson M, Wu J, Zhao N, Cherniack A, Hammerman P, Tward A, Pedamallu C, Saksena G, Jung J, Ojesina A, Carter S, Zack T, Schumacher S, Beroukhim R, Freeman S, Meyerson M, Cho J, Chin L, Getz G, Noble M, DiCara D, Zhang H, Heiman D, Gehlenborg N, Voet D, Lin P, Frazer S, Stojanov P, Liu Y, Zou L, Kim J, Lawrence M, Sougnez C, Lichtenstein L, Cibulskis K, Lander E, Gabriel S, Muzny D, Doddapaneni H, Kovar C, Reid J, Morton D, Han Y, Hale W, Chao H, Chang K, Drummond J, Gibbs R, Kakkar N, Wheeler D, Xi L, Ciriello G, Ladanyi M, Lee W, Ramirez R, Sander C, Shen R, Sinha R, Weinhold N, Taylor B, Aksoy B, Dresdner G, Gao J, Gross B, Jacobsen A, Reva B, Schultz N, Sumer S, Sun Y, Chan T, Morris L, Stuart J, Benz S, Ng S, Benz C, Yau C, Baylin S, Cope L, Danilova L, Herman J, Bootwalla M, Maglinte D, Laird P, Triche T, Weisenberger D, Van Den Berg D, Agrawal N, Bishop J, Boutros P, Bruce J, Byers L, Califano J, Carey T, Chen Z, Cheng H, Chiosea S, Cohen E, Diergaarde B, Egloff A, El-Naggar A, Ferris R, Frederick M, Grandis J, Guo Y, Haddad R, Hammerman P, Harris T, Hayes D, Hui A, Lee J, Lippman S, Liu F, McHugh J, Myers J, Ng P, Perez-Ordonez B, Pickering C, Prystowsky M, Romkes M, Saleh A, Sartor M, Seethala R, Seiwert T, Si H, Tward A, Van Waes C, Waggott D, Wiznerowicz M, Yarbrough W, Zhang J, Zuo Z, Burnett K, Crain D, Gardner J, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton C, Shelton T, Sherman M, Yena P, Black A, Bowen J, Frick J, Gastier-Foster J, Harper H, Lichtenberg T, Ramirez N, Wise L, Zmuda E, Baboud J, Jensen M, Kahn A, Pihl T, Pot D, Srinivasan D, Walton J, Wan Y, Burton R, Davidsen T, Demchok J, Eley G, Ferguson M, Shaw K, Ozenberger B, Sheth M, Sofia H, Tarnuzzer R, Wang Z, Yang L, Zenklusen J, Saller C, Tarvin K, Chen C, Bollag R, Weinberger P, Golusiński W, Golusiński P, Ibbs M, Korski K, Mackiewicz A, Suchorska W, Szybiak B, Wiznerowicz M, Burnett K, Curley E, Gardner J, Mallery D, Penny R, Shelton T, Yena P, Beard C, Mitchell C, Sandusky G, Agrawal N, Ahn J, Bishop J, Califano J, Khan Z, Bruce J, Hui A, Irish J, Liu F, Perez-Ordonez B, Waldron J, Boutros P, Waggott D, Myers J, Lippman S, Egea S, Gomez-Fernandez C, Herbert L, Bradford C, Carey T, Chepeha D, Haddad A, Jones T, Komarck C, Malakh M, McHugh J, Moyer J, Nguyen A, Peterson L, Prince M, Rozek L, Sartor M, Taylor E, Walline H, Wolf G, Boice L, Chera B, Funkhouser W, Gulley M, Hackman T, Hayes D, Hayward M, Huang M, Rathmell W, Salazar A, Shockley W, Shores C, Thorne L, Weissler M, Wrenn S, Zanation A, Chiosea S, Diergaarde B, Egloff A, Ferris R, Romkes M, Seethala R, Brown B, Guo Y, Pham M, Yarbrough W. Characterization of HPV and host genome interactions in primary head and neck cancers. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 15544-15549. PMID: 25313082, PMCID: PMC4217452, DOI: 10.1073/pnas.1416074111.Peer-Reviewed Original ResearchConceptsHuman genomeNeck cancerHigh-risk HPV types 16Next-generation RNAViral gene expressionMRNA transcript abundanceHPV types 16Genic regionsSubset of headGenome interactionsDNA copy numberIntrachromosomal rearrangementsTranscript abundanceDNA methylationStatistical enrichmentHost genomeHuman papillomavirus sequencesIntegration eventsGenomeGene expressionViral oncoproteinsCopy numberHPV infectionViral genomeClinical features
2011
Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1
Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, Xie TX, Zhang J, Wang J, Zhang N, El-Naggar AK, Jasser SA, Weinstein JN, Treviño L, Drummond JA, Muzny DM, Wu Y, Wood LD, Hruban RH, Westra WH, Koch WM, Califano JA, Gibbs RA, Sidransky D, Vogelstein B, Velculescu VE, Papadopoulos N, Wheeler DA, Kinzler KW, Myers JN. Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1. Science 2011, 333: 1154-1157. PMID: 21798897, PMCID: PMC3162986, DOI: 10.1126/science.1206923.Peer-Reviewed Original ResearchMeSH KeywordsCarcinomaCarcinoma, Squamous CellCell Cycle ProteinsCodon, NonsenseExonsF-Box ProteinsF-Box-WD Repeat-Containing Protein 7Gene DosageGenes, p53Genes, Tumor SuppressorHead and Neck NeoplasmsHumansINDEL MutationMutationMutation, MissenseNeoplasms, Squamous CellOligonucleotide Array Sequence AnalysisOncogenesPapillomaviridaePapillomavirus InfectionsReceptor, Notch1Sequence Analysis, DNASmokingSquamous Cell Carcinoma of Head and NeckUbiquitin-Protein LigasesConceptsNeck squamous cell carcinomaSquamous cell carcinomaCell carcinomaHuman papillomavirusHPV-positive tumorsWhole-exome sequencingMore mutationsPrimary tumorCommon cancerMultiple tumorsTobacco useTumor typesTumorsTumor suppressor geneExome sequencingGene copy number analysisNotch1Copy number analysisPatientsCarcinomaInactivating mutationCancerSuppressor geneMutationsGenetic origin