2018
CDKN2A/p16 deletion in head and neck cancer cells is associated with Cdk2 activation, replication stress, and vulnerability to Chk1 inhibition
Gadhikar MA, Zhang J, Shen L, Rao X, Wang J, Zhao M, Kalu NN, Johnson FM, Byers LA, Heymach J, Hittelman WN, Udayakumar D, Pandita RK, Pandita TK, Pickering CR, Redwood AB, Piwnica-Worms H, Schlacher K, Frederick MJ, Myers JN. CDKN2A/p16 deletion in head and neck cancer cells is associated with Cdk2 activation, replication stress, and vulnerability to Chk1 inhibition. Cancer Research 2018, 78: canres.2802.2017. PMID: 29229598, PMCID: PMC5811346, DOI: 10.1158/0008-5472.can-17-2802.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsApoptosisBiomarkers, TumorCarcinoma, Squamous CellCell ProliferationCheckpoint Kinase 1Cyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18DNA ReplicationEnzyme ActivationEnzyme InhibitorsHead and Neck NeoplasmsHumansS PhaseSequence DeletionTumor Cells, CulturedConceptsBiomarker-driven strategiesHNSCC patientsS-phase arrestEarly S-phase arrestCDKN2A/Neck squamous cell carcinoma cell linesSquamous cell carcinoma cell linesSingle-agent activityCell carcinoma cell linesCell linesHypersensitive cellsCarcinoma cell linesCdk2 activationHNSCC cellsDrug dosesCertain tumorsCancer ResCopy number lossCausative factorsHypersensitivityCHK inhibitorsPanel medianMonotherapyDrug ICReplication stress
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 Res
2015
Down‐regulation of malic enzyme 1 and 2: Sensitizing head and neck squamous cell carcinoma cells to therapy‐induced senescence
Woo SH, Yang LP, Chuang HC, Fitzgerald A, Lee HY, Pickering C, Myers JN, Skinner HD. Down‐regulation of malic enzyme 1 and 2: Sensitizing head and neck squamous cell carcinoma cells to therapy‐induced senescence. Head & Neck 2015, 38: e934-e940. PMID: 25994759, DOI: 10.1002/hed.24129.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellCell Line, TumorCellular SenescenceCyclin-Dependent Kinase Inhibitor p21Down-RegulationGene Expression Regulation, NeoplasticGene Knockdown TechniquesHead and Neck NeoplasmsHumansMalate DehydrogenaseMetforminRadiation, IonizingReactive Oxygen SpeciesTumor Suppressor Protein p53ConceptsTherapy-induced senescenceOverall survivalReactive oxygen speciesNeck squamous cell carcinomaSquamous cell carcinomaPoor overall survivalPotential therapeutic benefitHNSCC cell linesAntioxidant N-acetyl cysteineN-acetyl cysteinePoor outcomeCell carcinomaPatient outcomesHNSCC cellsGeneration of ROSTherapeutic benefitME2 expressionInduction of senescenceHNSCCP53 statusHigh expressionEnzyme expressionCell linesOxygen speciesOutcomes
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
Individualizing antimetabolic treatment strategies for head and neck squamous cell carcinoma based on TP53 mutational status
Sandulache VC, Skinner HD, Ow TJ, Zhang A, Xia X, Luchak JM, Wong L, Pickering CR, Zhou G, Myers JN. Individualizing antimetabolic treatment strategies for head and neck squamous cell carcinoma based on TP53 mutational status. Cancer 2011, 118: 711-721. PMID: 21720999, PMCID: PMC3188683, DOI: 10.1002/cncr.26321.Peer-Reviewed Original ResearchConceptsMitochondrial respirationGlycolytic dependenceHNSCC cellsAltered tumor cell metabolismGlycolytic inhibitionTumor suppressor geneTumor cell metabolismTP53 mutational statusMitochondrial reserveInhibition of respirationMetabolic shiftCell metabolismCellular resistanceSuppressor geneHNSCC cell linesMutational statusGlycolytic fluxCell linesRespirationNeck squamous cell carcinomaMutationsGlycolysisCellsClonogenic assayRadioresistance