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
2020
Functionally 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 chance
2015
Evolutionary 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 mutationsPatientsTumorsEvolutionary 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 responseScoresComprehensive genomic characterization of head and neck squamous cell carcinomas
Lawrence M, Sougnez C, Lichtenstein L, Cibulskis K, Lander E, Gabriel S, Getz G, Ally A, Balasundaram M, Birol I, Bowlby R, Brooks D, 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, Gordon 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, Hong Fan Y, Liu J, Wang K, Todd Auman J, Balu S, Bodenheimer T, Buda E, Neil Hayes D, Hoadley K, Hoyle A, Jefferys S, Jones C, Kimes P, Liu Y, 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, Sekhar 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, Sougnez C, Gabriel S, Lawrence M, 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, Arman Aksoy B, Dresdner G, Gao J, Gross B, Jacobsen A, Reva B, Schultz N, Onur 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, Averett Byers L, Califano J, Carey T, Chen Z, Cheng H, Chiosea S, Cohen E, Diergaarde B, Marie Egloff A, El-Naggar A, Ferris R, Frederick M, Grandis J, Guo Y, Haddad R, Hammerman P, Harris T, Neil Hayes D, Hui A, Jack Lee J, Lippman S, Liu F, McHugh J, Myers J, Kwok Shing 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, Leraas K, 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, Mills Shaw K, Ozenberger B, Sheth M, Sofia H, Tarnuzzer R, Wang Z, Yang L, Claude 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, William W, 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, Neil Hayes D, Hayward M, Huang M, Kimryn Rathmell W, Salazar A, Shockley W, Shores C, Thorne L, Weissler M, Wrenn S, Zanation A, Chiosea S, Diergaarde B, Marie Egloff A, Ferris R, Romkes M, Seethala R, Brown B, Guo Y, Pham M, Yarbrough W. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015, 517: 576-582. PMID: 25631445, PMCID: PMC4311405, DOI: 10.1038/nature14129.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellDNA Copy Number VariationsDNA, NeoplasmFemaleGene Expression Regulation, NeoplasticGenome, HumanGenomicsHead and Neck NeoplasmsHumansMaleMolecular Targeted TherapyMutationOncogenesRNA, NeoplasmSignal TransductionSquamous Cell Carcinoma of Head and NeckTranscription FactorsConceptsNeck squamous cell carcinomaSquamous cell carcinomaCell carcinomaCopy number alterationsMutations of HRASFavorable clinical outcomeFrequent copy number alterationsComprehensive genomic characterizationNumber alterationsFunction TP53 mutationsCancer Genome AtlasSomatic genomic alterationsClinical outcomesLaryngeal tumorsOral cavityFunction alterationsTP53 mutationsCandidate alterationsOncogene PIK3CALoss of TRAF3Novel alterationsCDKN2A inactivationGenome AtlasGenomic alterationsDomain mutations
2014
Sequencing HNC: Emergence of Notch Signaling
Pickering C, Ow T, Myers J. Sequencing HNC: Emergence of Notch Signaling. Current Cancer Research 2014, 303-323. DOI: 10.1007/978-1-4614-8815-6_15.ChaptersTumor suppressor geneSuppressor geneImportant tumor suppressor geneRecent sequencing studiesNeck cancer progressionIdentification of mutationsBiology of headSurprising new findingsNotch signalingGene Notch1Notch pathwaySequencing studiesCancer progressionGenomic abnormalitiesChromosomal alterationsMutationsGenesNotch1PathwayFrequent eventNew lightNeck cancerSignalingBiologyTP53 mutations
2013
Chk1/2 Inhibition Overcomes the Cisplatin Resistance of Head and Neck Cancer Cells Secondary to the Loss of Functional p53
Gadhikar MA, Sciuto MR, Alves MV, Pickering CR, Osman AA, Neskey DM, Zhao M, Fitzgerald AL, Myers JN, Frederick MJ. Chk1/2 Inhibition Overcomes the Cisplatin Resistance of Head and Neck Cancer Cells Secondary to the Loss of Functional p53. Molecular Cancer Therapeutics 2013, 12: 1860-1873. PMID: 23839309, PMCID: PMC3955083, DOI: 10.1158/1535-7163.mct-13-0157.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Squamous CellCell Line, TumorCellular SenescenceCheckpoint Kinase 1Checkpoint Kinase 2CisplatinDNA DamageDrug Resistance, NeoplasmHead and Neck NeoplasmsHumansMitosisMolecular Targeted TherapyMutationProtein Kinase InhibitorsProtein KinasesSignal TransductionThiophenesTumor Suppressor Protein p53UreaConceptsHNSCC cellsCisplatin resistanceAdvanced stage squamous cell carcinomaStage squamous cell carcinomaSquamous cell carcinomaTreatment of HNSCCP53 mutant tumorsLoss of TP53Neck cancer cellsWild-type TP53Multimodality therapyStandard therapyTreatment failureCell carcinomaPreclinical dataHNSCC tumorsTherapeutic advantageTP53 mutationsP53 mutationsTargeted inhibitionPersonalized approachHNSCCP53-deficient cellsKinase inhibitorsSynthetic lethal manner
2011
Disruptive TP53 Mutation Is Associated with Aggressive Disease Characteristics in an Orthotopic Murine Model of Oral Tongue Cancer
Sano D, Xie TX, Ow TJ, Zhao M, Pickering CR, Zhou G, Sandulache VC, Wheeler DA, Gibbs RA, Caulin C, Myers JN. Disruptive TP53 Mutation Is Associated with Aggressive Disease Characteristics in an Orthotopic Murine Model of Oral Tongue Cancer. Clinical Cancer Research 2011, 17: 6658-6670. PMID: 21903770, PMCID: PMC3207013, DOI: 10.1158/1078-0432.ccr-11-0046.Peer-Reviewed Original ResearchConceptsDisruptive TP53 mutationsCervical lymph node metastasisOral tongue cancerLymph node metastasisOrthotopic murine modelHNSCC cell linesTP53 mutationsNode metastasisTongue cancerMurine modelCell linesTumor growthNeck squamous cell carcinoma cell linesSquamous cell carcinoma cell linesAggressive disease characteristicsCell carcinoma cell linesFaster tumor growthPoor patient outcomesP53 protein expressionTP53 mutation statusBehavior of tumorsWild-type TP53Western blot analysisOral tongueShorter survival