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
Mutations 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
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