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Mechanisms and Targeted Therapy of NRF2-high Esophageal Squamous Cell Carcinoma
Organization CORIELL INSTITUTE FOR MEDICAL RESEARCHLocation CAMDEN, UNITED STATESPosted 1 Jun 2020Deadline 31 Dec 2025 ⚠️
NIHUS FederalResearch GrantFY20251-Phosphatidylinositol 3-Kinase3-D3-Dimensional3DAffectAnabolismAnimal ModelAnimal Models and Related StudiesAntioncogene Protein p53ApoptosisApoptosis PathwayArchitectureAutomobile DrivingBasal Transcription FactorBasal transcription factor genesBiochemistryBiologic ModelsBiological ChemistryBiological ModelsBiologyBody TissuesCDK4ICDKN2CDKN2 GenesCDKN2ACDKN2A geneCMM2CUL3CUL3 geneCancer CauseCancer EtiologyCancersCarcinoma CellCell BodyCell Communication and SignalingCell LineCell SignalingCell modelCellLineCellsCellular Tumor Antigen P53Cellular biologyCellular modelCessation of lifeClinicCyclin-Dependent Kinase Inhibitor 2A GeneDNA mutationDaraprimDataData SetDeathDevelopmentDiagnosisDrug Metabolic DetoxicationDrug Metabolic DetoxificationDrug ScreeningEngineering / ArchitectureEpithelial CellsEpitheliumEsophageal Epidermoid CarcinomaEsophageal SCCEsophageal Squamous Cell CarcinomaEsophagusEventExperimental ModelsExpression ProfilingFutureGene TranscriptionGeneral Transcription Factor GeneGeneral Transcription FactorsGeneralized GrowthGenesGeneticGenetic ChangeGenetic TranscriptionGenetic defectGenetic mutationGrowthHeterograftHeterologous TransplantationHumanHyperactivityHyperplasiaHyperplasticINK4INK4AIn VitroIntermediary MetabolismIntracellular Communication and SignalingKIAA0617KinasesLesionLoxP-flanked alleleLungLung Respiratory SystemMTS1MTS1 GenesMalignant Epithelial CellMalignant NeoplasmsMalignant TumorMalignant Tumor of the LungMalignant neoplasm of lungMetabolic Drug DetoxicationsMetabolic GlycosylationMetabolic ProcessesMetabolismMetabolism of Toxic AgentsMetastasisMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic TumorMiceMice MammalsModel SystemModelingModern ManMolecularMultiomic DataMurineMusMutateMutationNeoplasm MetastasisNormal CellOncogenicOncoprotein p53OrganoidsP53PI-3 KinasePI-3K/AKTPI3-KinasePI3CGPI3K-AlphaPI3K/AKTPI3KGammaPI3kPIK3PIK3-AlphaPIK3CAPIK3CA genePIK3CGPIK3CG genePathway interactionsPatientsPharmacological StudyPharmacologyPharmacology StudyPhasePhenotypePhosphatidylinositol 3-KinasePhosphatidylinositol 3-Kinase, Catalytic, 110-kD, AlphaPhosphatidylinositol 3-Kinase, Catalytic, AlphaPhosphatidylinositol-3-OH KinasePhosphoinositide 3-HydroxykinasePhosphoprotein P53Phosphoprotein pp53Phosphotransferase GenePhosphotransferasesPreventiveProgrammed Cell DeathProliferatingProtein TP53ProteomicsPtdIns 3-KinasePulmonary CancerPulmonary malignant NeoplasmPyrimethaminePyruvate KinaseRNA ExpressionRNA SeqRNA sequencingRNAseqRecurrenceRecurrentRegulationReportingResearchSCC of the EsophagusSecondary NeoplasmSecondary TumorSignal PathwaySignal TransductionSignal Transduction SystemsSignalingSquamous Cell Carcinoma of the EsophagusStaining methodStainsStrains Cell LinesStressSurvey InstrumentSurveysSurvival RateTP16TP53TP53 geneTRP53TSG9ATamoxifenTestingTherapeuticTherapeutic AgentsTissue ArraysTissue ChipTissue GrowthTissue MicroarrayTissuesTranscriptionTranscription Factor Proto-OncogeneTranscription factor genesTranslatingTransphosphorylasesTumor PromotersTumor Protein p53Tumor Protein p53 GeneType I Phosphatidylinositol KinaseType III Phosphoinositide 3-KinaseUnited StatesValidationWorkXenograftXenograft procedureXenotransplantationadvanced diseaseadvanced illnessbiological signal transductionbiosynthesiscancer metastasiscancer progressioncancer typecell biologycultured cell linedesigndesigningdetoxificationdevelopmentaldifferential expressiondifferentially expresseddrivingempowermentexperimentexperimental researchexperimental studyexperimentsfloxedfloxed allelegene locusgenetic locusgenome mutationgenomic locationgenomic locusglycosylationin vivoinhibitorinsightlife spanlifespanlung cancermalignancymembermetabolism measurementmetabolomicsmetabonomicsmodel of animalmultiple omic dataneoplasm progressionneoplasm/cancerneoplastic progressionnew drug targetnew drug treatmentsnew druggable targetnew drugsnew pharmacological therapeuticnew pharmacotherapy targetnew therapeutic targetnew therapeuticsnew therapynew therapy targetnext generation therapeuticsnovelnovel drug targetnovel drug treatmentsnovel druggable targetnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel pharmacotherapy targetnovel therapeutic targetnovel therapeuticsnovel therapynovel therapy targetontogenyp110-Alphap14ARFp16 Genesp16INK4 Genesp16INK4A Genesp16INK4ap53 Antigenp53 Genesp53 Tumor Suppressorpathwaypharmacologicphosphoenol transphosphorylasephosphoenolpyruvate kinaseprogramsprotein p53responsesmall molecular inhibitorsmall moleculesmall molecule inhibitorsynergismtargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic evaluationtherapeutic testingthree dimensionaltranscription factortranscriptional differencestranscriptome sequencingtranscriptomic sequencingtumor cell metastasistumor progressionvalidationsxeno-transplantxeno-transplantation
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Description preview
This multiple-PI R01 proposal is designed to incorporate genetic and pharmacological approaches to
understand the mechanisms of NRF2 hyperactivation in ESCC and to develop targeted therapy for Nrf2high
ESCC. We believe Nrf2 and kinases are functionally interrelated, and thus cooperatively contribute to ESCC.
In this proposal, we aim to…
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