grant
The SIK2 Inhibitor GRN-300 Enhances PARP Inhibitor Sensitivity and Cytotoxic T-Cell Function in Ovarian Cancer
Organization UNIVERSITY OF TX MD ANDERSON CAN CTRLocation HOUSTON, UNITED STATESPosted 19 Sept 2023Deadline 31 Jul 2028
NIHUS FederalResearch GrantFY2025(IFN) α(IFN)-α(IFN)α(TNF)-αAbscissionAffectAlferonAnzataxAsotaxB cell differentiation factorB cell stimulating factor 2B-Cell Differentiation FactorB-Cell Differentiation Factor GeneB-Cell Differentiation Factor-2B-Cell Stimulatory Factor 2 GeneB-Cell Stimulatory Factor-2B7-H1BCDFBRCA 1/2BRCA1/2BSF-2BSF-2 GeneBSF2BSF2 GeneBeta Proprotein Interleukin 1Beta-2 Gene InterferonBindingBiopsyBloodBlood Reticuloendothelial SystemBone MarrowBone Marrow Reticuloendothelial SystemBristaxolCBDCACD11bCD25CD274CD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCR3ACachectinCancer ModelCancer cell lineCancerModelCancersCarboplatinCarboplatinoCell BodyCell FunctionCell PhysiologyCell ProcessCell-Mediated Lympholytic CellsCellsCellular FunctionCellular PhysiologyCellular ProcessChromatinClinicalClinical TrialsCo-StimulatorCostimulatorCytolytic T-CellCytotoxic T CellCytotoxic T-LymphocytesDNADNA DamageDNA Damage RepairDNA InjuryDNA RepairDNA Repair GeneDNA Repair InhibitionDNA Repair PathwayDNA mutationDNA repair proteinDNA replication forkDataDeoxyribonucleic AcidDiagnosisDoseDrug KineticsEXO1EXO1 exonucleaseEXO1 geneEnhancersEpidermal Thymocyte Activating FactorExcisionExhibitsExonuclease 1ExtirpationFANCD2FANCD2 proteinFLJ11330FOXP3FOXP3 geneFallopian Tube CancerFanconi anemia complementation group D2Forkhead Box P3FutureGene TranscriptionGenesGenetic ChangeGenetic TranscriptionGenetic defectGenetic mutationGoalsHDACHDAC ProteinsHDAC4HDAC4 geneHDAC5HDAC5 geneHDAC7HDAC7 histone deacetylaseHDACAHEX1HEX1 GeneHPGFHSF GeneHepatocyte Stimulatory Factor GeneHepatocyte-Stimulating FactorHeterograftHeterologous TransplantationHistone DeacetylaseHistone Deacetylase 4Histone Deacetylase 5Histone Deacetylase AHomologous Recombinational RepairHumanHybridoma Growth FactorHybridoma Growth Factor GeneIFN AlphaIFN αIFN-GammaIFN-beta 2IFN-gIFN-regulatory factor 3IFN-αIFN-γIFNB2IFNB2 GeneIFNGIFNaIFNαIFNγIL-1 betaIL-1 βIL-1-bIL-1βIL-2IL-6IL-6 GeneIL1-BetaIL1-βIL1B ProteinIL1F2IL1βIL2 ProteinIL2RIL2RAIL2RA geneIL6IL6 ProteinIL6 geneIRF-3 proteinIRF3IRF3 geneITGAMITGAM geneImmune InterferonImmune MarkersImmune mediated therapyImmunologic MarkersImmunologically Directed TherapyImmunomodulationImmunotherapyImpairmentInfiltrationInnate ImmunityInterferon Alfa-n3Interferon GammaInterferon Regulatory Factor 3Interferon Type IIInterferon-αInterleukin 1betaInterleukin 2Interleukin 2 PrecursorInterleukin 6 (Interferon, Beta 2) GeneInterleukin IIInterleukin-1 betaInterleukin-1βInterleukin-2Interleukin-6Interleukin-6 GeneInterleukine 2Interleukine 2 PrecursorInterleukine IIJM2KinasesLeukocyte InterferonLymphoblast InterferonLymphoblastoid InterferonLymphocyte Mitogenic FactorLytotoxicityMAC1AMDACCMGI-2MO1AMacrophage-Derived TNFMalignant CellMalignant NeoplasmsMalignant Ovarian NeoplasmMalignant Ovarian TumorMalignant TumorMalignant Tumor of the OvaryMalignant fallopian tube tumorMalignant neoplasm of fallopian tubeMalignant neoplasm of ovaryMaximal Tolerated DoseMaximally Tolerated DoseMaximum Tolerated DoseMediatingMiceMice MammalsMitogenic FactorModelingModern ManMolecularMolecular InteractionMonocyte-Derived TNFMorbidityMorbidity - disease rateMurineMusMuscle CellsMutationMyeloid Differentiation-Inducing ProteinMyeloid-derived suppressor cellsMyelosuppressionMyocytesNF-Kb-Activating Kinase GeneNamesNative ImmunityNatural ImmunityNon-Specific ImmunityNonspecific ImmunityNuclearNucleic Acid Regulator RegionsNucleic Acid Regulatory SequencesOrganoidsOutcomeOvarianOvary CancerPARP InhibitorPARP-1 inhibitorPARPiPBMCPD 1PD-1PD-L1PD1PDL-1PDX modelPaclitaxelPaclitaxel (Taxol)Pathway interactionsPatient derived xenograftPatientsPeripheral Blood Mononuclear CellPeritonealPharmacodynamicsPharmacokineticsPhasePhase 1a TrialPhase 1b TrialPhase Ia TrialPhase Ib TrialPhosphorylationPhosphotransferase GenePhosphotransferasesPlasmacytoma Growth FactorPlayPoly(ADP-ribose) Polymerase InhibitorPoly(ADP-ribose) polymerase 1 inhibitorPraxelPreinterleukin 1 BetaPrimary NeoplasmPrimary TumorProgrammed Cell Death 1 Ligand 1Programmed Death Ligand 1Progression-Free SurvivalsProtein PhosphorylationRNA ExpressionRNA SeqRNA sequencingRNAseqRecombination RepairRecurrenceRecurrentRegulatory RegionsRegulatory T-LymphocyteRelapseRemovalResistanceResistance developmentResistant developmentSCURFINSafetySamplingSecond LookSecond Look SurgerySiteSodium ChlorideStimulator of Interferon GenesSubcellular ProcessSurgical RemovalSurgical RevisionT cell growth factorT cell infiltrationT-Cell Growth FactorT-Cell Stimulating FactorT-CellsT-LymphocyteT2KT8 CellsT8 LymphocytesTBK1TBK1 geneTCGFRTGF-Beta 1TGF-Beta1TGFBTGFB1TGFB1 geneTNFTNF ATNF AlphaTNF geneTNF-αTNFATNFαTaxolTaxol ATaxol KonzentratTestingThymocyte Stimulating FactorToxic effectToxicitiesTranscriptionTransforming Growth Factor Beta 1TransphosphorylasesTregTumor Necrosis FactorTumor Necrosis Factor-alphaUniversity of Texas M D Anderson Cancer CenterUniversity of Texas MD Anderson Cancer CenterUnscheduled DNA SynthesisWomanXenograftXenograft ModelXenograft procedureXenotransplantationadaptive immunityanti-cancer immunotherapyanti-tumor immune responseanticancer immunotherapybrca genecGAMP STINGcGAMP-STINGcGAMP/STINGcGAS/STINGcancer cellcancer immunotherapycancer typecheck point blockadecheckpoint blockadechemotherapyclinical developmentcohortconventional therapyconventional treatmentcyclic GMP-AMP synthase/STINGcytokinecytotoxicitydeveloping resistanceeffective therapyeffective treatmentexperiencegenetic regulatory elementgenome mutationhExoIhomologous recombinationhomologous recombination deficiencyhomologous recombination repair deficiencyhuman HDAC5 proteinhuman NY-CO-9 proteinhuman histone deacetylase 5immune check point blockadeimmune checkpoint blockadeimmune modulationimmune regulationimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based biomarkersimmune-based cancer therapiesimmune-based therapiesimmune-based treatmentsimmuno therapyimmunologic reactivity controlimmunological biomarkersimmunological markersimmunomodulatoryimmunoregulationimmunoregulatoryimmunosuppressive myeloid cellsimmunotherapy for cancerimmunotherapy of cancerimprovedinhibiting antibodyinhibitorinterferon beta 2killer T celllFN-GammamHDAC7mRNA Expressionmalignancymortalitymouse modelmurine modelmyeloid suppressor cellsmyeloid-derived suppressive cellsnamenamednamingneoplasm/cancernovelovarian cancerpathwaypatient derived xenograft modelphase 1 trialphase I trialpre-clinical studypreclinical studypreventpreventingprimary outcomeprogrammed cell death 1programmed cell death ligand 1programmed cell death protein 1programmed cell death protein ligand 1programmed death 1protein death-ligand 1rad2 nuclease family member, homolog of S. cerevisiae exonuclease 1recombinational repairregulatory T-cellsrepairrepairedreplication forkresectionresistantresponserestorationsaltsalt-inducible kinasesle2suppressive myeloid cellssystemic lupus erythematosus susceptibility 2targeted agenttherapeutic outcometherapy outcomethymus derived lymphocytetranscriptome sequencingtranscriptomic sequencingtransforming growth factor beta1tumorxeno-transplantxeno-transplantationxenograft transplant modelxenotransplant model
Description preview
Ovarian cancer remains a major cause of morbidity and mortality, affecting nearly 300,000 women globally each year. Poor outcomes are primarily driven by delayed diagnosis and the development of resistance to standard chemotherapy with carboplatin and paclitaxel. In the previous SPORE cycle, we developed and initiated a firstin-human clinical…
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