2023
HRAS Mutations Define a Distinct Subgroup in Head and Neck Squamous Cell Carcinoma
Coleman N, Marcelo K, Hopkins J, Khan N, Du R, Hong L, Park E, Balsara B, Leoni M, Pickering C, Myers J, Heymach J, Albacker L, Hong D, Gillison M, Le X. HRAS Mutations Define a Distinct Subgroup in Head and Neck Squamous Cell Carcinoma. JCO Precision Oncology 2023, 7: e2200211. PMID: 36603172, PMCID: PMC9928766, DOI: 10.1200/po.22.00211.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaMD Anderson Cancer CenterSquamous cell carcinomaAnderson Cancer CenterCo-occurring mutationsClinical courseSurvival outcomesCancer CenterCell carcinomaShorter disease-free survivalPoor clinic outcomePrimary definitive treatmentTherapeutic combination strategiesDisease-free survivalPoor clinical outcomePatient demographic informationImproved OSDefinitive treatmentMedian ageOverall survivalFoundation MedicineMale patientsClinical outcomesClinic outcomesTreatment response
2022
Clinical Trial Development in TP53-Mutated Locally Advanced and Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma
Rodriguez CP, Kang H, Geiger JL, Burtness B, Chung CH, Pickering CR, Fakhry C, Le QT, Yom SS, Galloway TJ, Golemis E, Li A, Shoop J, Wong S, Mehra R, Skinner H, Saba NF, Flores ER, Myers JN, Ford JM, Karchin R, Ferris RL, Kunos C, Lynn JM, Malik S. Clinical Trial Development in TP53-Mutated Locally Advanced and Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. Journal Of The National Cancer Institute 2022, 114: 1619-1627. PMID: 36053203, PMCID: PMC9745425, DOI: 10.1093/jnci/djac163.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaSquamous cell carcinomaClinical trialsCell carcinomaTrial designTP53 mutationsNational Clinical Trials NetworkMetastatic disease settingsClinical trial developmentClinical Trials NetworkNovel therapeutic approachesNational Cancer InstituteMetastatic headTP53-mutated tumorsWorse outcomesClinical studiesFrequent genetic eventTherapeutic approachesCancer InstituteTrial developmentBreakout groupsPatientsDisease settingsBiomarker integrationTrials Network
2021
Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function
Kumar M, Molkentine D, Molkentine J, Bridges K, Xie T, Yang L, Hefner A, Gao M, Bahri R, Dhawan A, Frederick MJ, Seth S, Abdelhakiem M, Beadle BM, Johnson F, Wang J, Shen L, Heffernan T, Sheth A, Ferris RL, Myers JN, Pickering CR, Skinner HD. Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function. Nature Communications 2021, 12: 6340. PMID: 34732714, PMCID: PMC8566594, DOI: 10.1038/s41467-021-26570-8.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsApoptosisBiomarkers, TumorBRCA1 ProteinCell Line, TumorCREB-Binding ProteinE1A-Associated p300 ProteinGain of Function MutationHistone AcetyltransferasesHomologous RecombinationHumansMaleMice, NudeMutationNeoplasmsProtein DomainsSquamous Cell Carcinoma of Head and NeckXenograft Model Antitumor AssaysWhole-exome Sequencing in Penile Squamous Cell Carcinoma Uncovers Novel Prognostic Categorization and Drug Targets Similar to Head and Neck Squamous Cell CarcinomaClinical Implications of WES in Penile Squamous Carcinoma
Chahoud J, Gleber-Netto FO, McCormick BZ, Rao P, Lu X, Guo M, Morgan MB, Chu RA, Martinez-Ferrer M, Eterovic AK, Pickering CR, Pettaway CA. Whole-exome Sequencing in Penile Squamous Cell Carcinoma Uncovers Novel Prognostic Categorization and Drug Targets Similar to Head and Neck Squamous Cell CarcinomaClinical Implications of WES in Penile Squamous Carcinoma. Clinical Cancer Research 2021, 27: 2560-2570. PMID: 33441293, DOI: 10.1158/1078-0432.ccr-20-4004.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorCase-Control StudiesComputational BiologyDisease ManagementDisease SusceptibilityExome SequencingHumansMaleMiddle AgedMolecular Targeted TherapyMutationNeoplasm GradingNeoplasm StagingPenile NeoplasmsPrognosisSquamous Cell Carcinoma of Head and NeckConceptsPenile squamous cell carcinomaSquamous cell carcinomaCell carcinomaHuman papilloma virus testingNeck squamous cell carcinomaNotch pathway alterationsMutation signaturesTumor mutation burdenWorse overall survivalLimited treatment optionsWhole-exome sequencing analysisPenile squamous carcinomaPotential clinical implicationsMutational signaturesDefective DNA mismatch repairCancer Genome Atlas studyWhole-exome sequencingNovel druggable targetsDistinct mutational signaturesNormal penile tissuesOverall survivalWorse survivalHigh TMBSquamous carcinomaPenile tissue
2020
The mutational landscape of early‐ and typical‐onset oral tongue squamous cell carcinoma
Campbell BR, Chen Z, Faden DL, Agrawal N, Li RJ, Hanna GJ, Iyer NG, Boot A, Rozen SG, Vettore AL, Panda B, Krishnan NM, Pickering CR, Myers JN, Guo X, Kuhs K. The mutational landscape of early‐ and typical‐onset oral tongue squamous cell carcinoma. Cancer 2020, 127: 544-553. PMID: 33146897, PMCID: PMC7891879, DOI: 10.1002/cncr.33309.Peer-Reviewed Original ResearchConceptsOral tongue squamous cell carcinomaTongue squamous cell carcinomaSquamous cell carcinomaTongue cancerYounger patientsCell carcinomaTobacco useDriver genesOral tongue cancerPatient-related factorsCancer driver genesTongue cancer specimensAge of onsetMutational landscapeSomatic mutationsMutation signaturesYounger birth cohortsSomatic mutational burdenOlder patientsCancer Genome AtlasSmoking ratesMutational burdenCancer specimensMulticenter consortiumBirth cohortFunctionally impactful TP53 mutations are associated with increased risk of extranodal extension in clinically advanced oral squamous cell carcinoma
Gleber‐Netto F, Neskey D, de Mattos Costa A, Kataria P, Rao X, Wang J, Kowalski LP, Pickering CR, Dias‐Neto E, Myers JN. Functionally impactful TP53 mutations are associated with increased risk of extranodal extension in clinically advanced oral squamous cell carcinoma. Cancer 2020, 126: 4498-4510. PMID: 32797678, DOI: 10.1002/cncr.33101.Peer-Reviewed Original ResearchConceptsAdvanced oral squamous cell carcinomaOral squamous cell carcinomaExtranodal extensionSquamous cell carcinomaTP53 mutationsAncillary biomarkersCell carcinomaCancer Genome Atlas (TCGA) cohortPostoperative adjuvant therapyTP53 mutation statusWild-type TP53Adjuvant therapyCancer Genome AtlasCommon genetic eventClinicopathologic characteristicsClinical outcomesP53 protein functionPatient managementTreatment decisionsClinical challengeTherapeutic approachesPatientsMutation statusHeterogeneous groupIncreased chanceIdentifying 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
Disruption of TP63-miR-27a* Feedback Loop by Mutant TP53 in Head and Neck Cancer
Chari NS, Ivan C, Le X, Li J, Mijiti A, Patel AA, Osman AA, Peterson CB, Williams MD, Pickering CR, Caulin C, Myers JN, Calin GA, Lai SY. Disruption of TP63-miR-27a* Feedback Loop by Mutant TP53 in Head and Neck Cancer. Journal Of The National Cancer Institute 2019, 112: 266-277. PMID: 31124563, PMCID: PMC7073912, DOI: 10.1093/jnci/djz097.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesChromatin ImmunoprecipitationFeedback, PhysiologicalHead and Neck NeoplasmsHumansMicroRNAsMouth NeoplasmsMutationNeoplasm StagingPromoter Regions, GeneticSquamous Cell Carcinoma of Head and NeckSurvival RateTranscription FactorsTranscription, GeneticTumor Suppressor Protein p53Tumor Suppressor ProteinsConceptsMutant TP53Neck squamous cell carcinomaSquamous cell carcinomaHNSCC cell linesInhibits tumor growthEpidermal growth factor receptorFrequent eventRole of TP53PI3K pathwayGrowth factor receptorCancer Genome AtlasCell carcinomaNeck cancerHNSCC samplesPoor survivalEpidermal growth factorTumor growthVivo findingsTumor progressionPatient samplesTumor samplesTumor survivalTumor cellsNormal tissuesNovel target
2018
Mutation allele frequency threshold does not affect prognostic analysis using next-generation sequencing in oral squamous cell carcinoma
Ma J, Fu Y, Tu YY, Liu Y, Tan YR, Ju WT, Pickering CR, Myers JN, Zhang ZY, Zhong LP. Mutation allele frequency threshold does not affect prognostic analysis using next-generation sequencing in oral squamous cell carcinoma. BMC Cancer 2018, 18: 758. PMID: 30041611, PMCID: PMC6057048, DOI: 10.1186/s12885-018-4481-8.Peer-Reviewed Original ResearchConceptsOral squamous cell carcinomaSquamous cell carcinomaPrognostic analysisOSCC patientsCell carcinomaMethodsForty-six patientsClinical outcome analysisNext-generation sequencingAllele frequency thresholdWild-type genotypeParaffin-embedded tissuesNon-synonymous mutationsAllele frequenciesClinical outcomesOutcome analysisPatientsPanel of cancerType genotypeSignificant differencesCarcinomaFrequency thresholdNotch1CDKN2AMutationsCASP8Comprehensive 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 arrestHigh-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma
Sandulache VC, Michikawa C, Kataria P, Gleber-Netto FO, Bell D, Trivedi S, Rao X, Wang J, Zhao M, Jasser S, Myers JN, Pickering CR. High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma. Clinical Cancer Research 2018, 24: 1727-1733. PMID: 29330202, PMCID: PMC5884733, DOI: 10.1158/1078-0432.ccr-17-0721.Peer-Reviewed Original ResearchConceptsOral cavity squamous cell carcinomaExtranodal extensionPrimary tumorDisease-free survivalPoor prognostic factorProspective clinical trialsSquamous cell carcinomaAggressive biological phenotypeClin Cancer ResHigh-risk mutationsPersonalized treatment decisionsWild-type TP53ENE statusOSCC dataPN0 tumorsCancer Genome AtlasLymph nodesPrognostic factorsClinical outcomesInstitutional cohortCell carcinomaClinical trialsPoor survivalTreatment decisionsTreatment selectionThe Integrated Genomic Landscape of Thymic Epithelial Tumors
Radovich M, Pickering CR, Felau I, Ha G, Zhang H, Jo H, Hoadley KA, Anur P, Zhang J, McLellan M, Bowlby R, Matthew T, Danilova L, Hegde AM, Kim J, Leiserson MDM, Sethi G, Lu C, Ryan M, Su X, Cherniack AD, Robertson G, Akbani R, Spellman P, Weinstein JN, Hayes DN, Raphael B, Lichtenberg T, Leraas K, Zenklusen JC, Network T, Ally A, Appelbaum E, Auman J, Balasundaram M, Balu S, Behera M, Beroukhim R, Berrios M, Blandino G, Bodenheimer T, Bootwalla M, Bowen J, Brooks D, Carcano F, Carlsen R, Carvalho A, Castro P, Chalabreysse L, Chin L, Cho J, Choe G, Chuah E, Chudamani S, Cibulskis C, Cope L, Cordes M, Crain D, Curley E, Defreitas T, Demchok J, Detterbeck F, Dhalla N, Dienemann H, Edenfield W, Facciolo F, Ferguson M, Frazer S, Fronick C, Fulton L, Fulton R, Gabriel S, Gardner J, Gastier-Foster J, Gehlenborg N, Gerken M, Getz G, Heiman D, Hobensack S, Holbrook A, Holt R, Hoyle A, Hutter C, Ittmann M, Jefferys S, Jones C, Jones S, Kasaian K, Kim J, Kimes P, Lai P, Laird P, Lawrence M, Lin P, Liu J, Lolla L, Lu Y, Ma Y, Maglinte D, Mallery D, Mardis E, Marra M, Martin J, Mayo M, Meier S, Meister M, Meng S, Meyerson M, Mieczkowski P, Miller C, Mills G, Moore R, Morris S, Mose L, Muley T, Mungall A, Mungall K, Naresh R, Newton Y, Noble M, Owonikoko T, Parker J, Paulaskis J, Penny R, Perou C, Perrin C, Pihl T, Radenbaugh A, Ramalingam S, Ramirez N, Rieker R, Roach J, Sadeghi S, Saksena G, Schein J, Schmidt H, Schumacher S, Shelton C, Shelton T, Shi Y, Shih J, Sica G, Silveira H, Simons J, Sipahimalani P, Skelly T, Sofia H, Soloway M, Stuart J, Sun Q, Tam A, Tan D, Tarnuzzer R, Thiessen N, Van Den Berg D, Vasef M, Veluvolu U, Voet D, Walter V, Wan Y, Wang Z, Warth A, Weis C, Weisenberger D, Wilkerson M, Wise L, Wong T, Wu H, Wu Y, Yang L, Zhang J, Zmuda E, Fujimoto J, Scapulatempo-Neto C, Moreira A, Hwang D, Huang J, Marino M, Korst R, Giaccone G, Gokmen-Polar Y, Badve S, Rajan A, Ströbel P, Girard N, Tsao M, Marx A, Tsao A, Loehrer P. The Integrated Genomic Landscape of Thymic Epithelial Tumors. Cancer Cell 2018, 33: 244-258.e10. PMID: 29438696, PMCID: PMC5994906, DOI: 10.1016/j.ccell.2018.01.003.Peer-Reviewed Original ResearchConceptsThymic epithelial tumorsEpithelial tumorsWorld Health Organization (WHO) histological subtypeAutoimmune disease myasthenia gravisDisease myasthenia gravisMuscle autoantigensThymic carcinomaMyasthenia gravisAutoimmune diseasesHistological subtypesAdult malignanciesTumoral overexpressionMarked prevalenceTumorsThymomaSubtypesEnrichment of mutationsGenomic landscapeBiological effectsGenomic hallmarksMolecular linkUnique associationAssociationMulti-platform analysisGravis
2017
Replication Stress Leading to Apoptosis within the S-phase Contributes to Synergism between Vorinostat and AZD1775 in HNSCC Harboring High-Risk TP53 Mutation
Tanaka N, Patel AA, Tang L, Silver NL, Lindemann A, Takahashi H, Jaksik R, Rao X, Kalu NN, Chen TC, Wang J, Frederick MJ, Johnson F, Gleber-Netto FO, Fu S, Kimmel M, Wang J, Hittelman WN, Pickering CR, Myers JN, Osman AA. Replication Stress Leading to Apoptosis within the S-phase Contributes to Synergism between Vorinostat and AZD1775 in HNSCC Harboring High-Risk TP53 Mutation. Clinical Cancer Research 2017, 23: 6541-6554. PMID: 28790110, PMCID: PMC5724758, DOI: 10.1158/1078-0432.ccr-17-0947.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCarcinoma, Squamous CellCell Cycle ProteinsCell Line, TumorCell ProliferationDNA DamageDNA ReplicationDrug SynergismFemaleHead and Neck NeoplasmsHistone Deacetylase InhibitorsHumansHydroxamic AcidsMiceMutationNuclear ProteinsPhosphorylationProtein-Tyrosine KinasesPyrazolesPyrimidinesPyrimidinonesRisk FactorsS PhaseSquamous Cell Carcinoma of Head and NeckTumor Suppressor Protein p53VorinostatConceptsOrthotopic mouse modelHNSCC cellsOral cancerMouse modelNeck squamous cell carcinomaSquamous cell carcinomaCombination of vorinostatProlongs animal survivalHNSCC cell linesClin Cancer ResClonogenic survival assaysAdvanced HNSCCAdvanced headStandard therapyCell carcinomaCure rateEffective therapyClinical investigationCell cycleP53 mutationsTumor growthVorinostatAnimal survivalAZD1775Cancer ResComprehensive Genomic Profiling of Metastatic Squamous Cell Carcinoma of the Anal Canal
Morris V, Rao X, Pickering C, Foo WC, Rashid A, Eterovic K, Kim T, Chen K, Wang J, Shaw K, Eng C. Comprehensive Genomic Profiling of Metastatic Squamous Cell Carcinoma of the Anal Canal. Molecular Cancer Research 2017, 15: 1542-1550. PMID: 28784613, PMCID: PMC5991496, DOI: 10.1158/1541-7786.mcr-17-0060.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAnimalsAnus NeoplasmsCarcinoma, Squamous CellClass I Phosphatidylinositol 3-KinasesDNA-Binding ProteinsExome SequencingFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiceMiddle AgedMutationNeoplasm MetastasisNeoplasm ProteinsNeoplasm TransplantationPapillomavirus InfectionsPatient-Specific ModelingTumor Suppressor Protein p53ConceptsMetastatic SCCAHuman papillomavirusMutation burdenPatient-derived xenograft modelsAvailable frozen tissueDistinct tumor subpopulationsAnti-EGFR treatmentTumor mutation burdenRare gastrointestinal malignancySquamous cell carcinomaNovel therapeutic approachesComprehensive molecular profilingLow mutation burdenComprehensive genomic characterizationMajority of casesWhole-exome sequencingGene mutation frequencyGastrointestinal malignanciesAdditional patientsAnal canalAnnual incidenceValidation cohortCell carcinomaStandard treatmentPrior infectionPrevalence of promoter mutations in the TERT gene in oral cavity squamous cell carcinoma
Chang K, Wang C, Pickering CR, Huang Y, Tsai C, Tsang N, Kao H, Cheng M, Myers JN. Prevalence of promoter mutations in the TERT gene in oral cavity squamous cell carcinoma. Head & Neck 2017, 39: 1131-1137. PMID: 28230921, DOI: 10.1002/hed.24728.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overCarcinoma, Squamous CellCohort StudiesDisease ProgressionDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMaleMiddle AgedMouth NeoplasmsMutationPrevalencePromoter Regions, GeneticReal-Time Polymerase Chain ReactionRetrospective StudiesRisk AssessmentStatistics, NonparametricSurvival AnalysisTaiwanTelomeraseConceptsOral cavity squamous cell carcinomaSquamous cell carcinomaTERT promoter mutationsAdjacent normal tissuesPromoter mutationsSomatic TERT promoter mutationsNormal tissuesC228T mutationTelomerase reverse transcriptase (TERT) promoterT mutationSCC tumor tissuesHuman telomerase reverse transcriptase (hTERT) promoterC250T mutationsReverse transcriptase promoterCell carcinomaSCC tumorsC228TTumor tissueTERT activityBetel nutTERT promoterTissuePresent studyMutationsSanger methodMutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors
Zhang M, Singh R, Peng S, Mazumdar T, Sambandam V, Shen L, Tong P, Li L, Kalu NN, Pickering CR, Frederick M, Myers JN, Wang J, Johnson FM. Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors. Cancer Letters 2017, 392: 71-82. PMID: 28126323, PMCID: PMC5404895, DOI: 10.1016/j.canlet.2017.01.024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisCarcinoma, Squamous CellCell Cycle ProteinsCell Line, TumorCell ProliferationCheckpoint Kinase 1Checkpoint Kinase 2Dose-Response Relationship, DrugG2 Phase Cell Cycle CheckpointsGenotypeHead and Neck NeoplasmsHumansLIM Domain ProteinsMice, NudeMolecular Targeted TherapyMutationNuclear ProteinsPhenotypeProtein Kinase InhibitorsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene ProteinsPteridinesPyrazolesPyrimidinesPyrimidinonesRas ProteinsRNA InterferenceSignal TransductionSmad4 ProteinSquamous Cell Carcinoma of Head and NeckThiophenesTime FactorsTransfectionTumor BurdenUreaXenograft Model Antitumor AssaysConceptsPolo-like kinase 1Cell linesLIM protein AjubaHNSCC cell linesInhibitor-induced apoptosisProtein expressionCell cycle inhibitorsCell cycle arrestKnockdown of PLK1Neck squamous cell carcinomaAjubaExogenous expressionNeck squamous cell carcinoma (HNSCC) tumorsSquamous cell carcinoma tumorsKinase 1HNSCC mouse modelSquamous cell carcinomaSubstrate inhibitionHigher drug dosesPotential candidate biomarkersGenomic alterationsMitotic inhibitorsPLK1 inhibitionSensitive cell linesMutations
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 genesCancerSalivaCarcinomaRecurrenceBiomarkersHPVOropharynxHNSCCEvolutionary 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 responseScoresEvolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer
Neskey DM, Osman AA, Ow TJ, Katsonis P, McDonald T, Hicks SC, Hsu TK, Pickering CR, Ward A, Patel A, Yordy JS, Skinner HD, Giri U, Sano D, Story MD, Beadle BM, El-Naggar AK, Kies MS, William WN, Caulin C, Frederick M, Kimmel M, Myers JN, Lichtarge O. Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer. Cancer Research 2015, 75: 1527-1536. PMID: 25634208, PMCID: PMC4383697, DOI: 10.1158/0008-5472.can-14-2735.Peer-Reviewed Original ResearchConceptsTP53 mutationsDistant metastasisP53 mutationsNeck squamous cell carcinomaSquamous cell carcinomaPoor survival outcomesAggressive tumor behaviorEvolutionary action scoreHigh-risk mutationsLung metastasesPrognostic significanceSurvival outcomesCell carcinomaNeck cancerClinical prognosisHigh incidenceLower riskTumor behaviorDecreased survivalKey cellular pathwaysTumor cellsMetastasisRisk mutationsPatientsTumorsComprehensive genomic characterization of head and neck squamous cell carcinomas
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