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Targeting BRCA1/2-deficient cancers with folate and vitamin C
Organization WEILL MEDICAL COLL OF CORNELL UNIVLocation NEW YORK, UNITED STATESPosted 1 Apr 2024Deadline 31 Mar 2026 ⚠️
NIHUS FederalResearch GrantFY20255,6,7,8-tetrahydrofolic acidActive OxygenAnti-OncogenesAntioncogenesAscorbic AcidAssayBRCA 1/2BRCA 1/2 mutationsBRCA deficientBRCA mutantsBRCA mutationsBRCA1BRCA1 Gene ProductBRCA1 ProteinBRCA1 geneBRCA1/2BRCA1/2 mutationsBRCA1/2mutBRCA2BRCA2 geneBRCAmutBioassayBiological AssayBloodBlood Reticuloendothelial SystemBody Weight decreasedBreastBreast CancerBreast Cancer 1 GeneBreast Cancer 1 Gene ProductBreast Cancer 2 GeneBreast Cancer PatientBreast Cancer Type 1 Susceptibility GeneBreast Cancer Type 1 Susceptibility ProteinBreast Cancer Type 2 Susceptibility GeneBreast Tumor PatientBreast-Ovarian Cancer ProteinCBDCACancer ModelCancer Suppressor GenesCancer TreatmentCancerModelCancersCarboplatinCarboplatinoCarcinogen-DNA AdductsCell BodyCell LineCellLineCellsCellular biologyCirculationClinical TrialsCrosslinkerDNADNA AdductsDNA DamageDNA Damage RepairDNA InjuryDNA Molecular BiologyDNA RepairDNA analysisDNA cross-linkDNA crosslinkDNA lesionDataDeoxyribonucleic AcidDiseaseDisorderDoseDrug KineticsEarly Onset Gene Breast Cancer 1Early Onset Gene Breast Cancer 2Early Onset Protein Breast Cancer 1EmerogenesFANCD1FolateFolic AcidFormaldehydeFormic AldehydeFoundationsGenerationsGenotoxinsGoalsHalf-LifeHereditary Breast Cancer 1Hereditary Breast Cancer 2ImmunohistochemistryImmunohistochemistry Cell/TissueImmunohistochemistry Staining MethodIn VitroIntermediary MetabolismKidneyKidney Urinary SystemLeadLytotoxicityMalignant Breast NeoplasmMalignant CellMalignant Neoplasm TherapyMalignant Neoplasm TreatmentMalignant NeoplasmsMalignant Ovarian NeoplasmMalignant Ovarian TumorMalignant TumorMalignant Tumor of the OvaryMalignant neoplasm of ovaryManipulation TherapyManipulative TherapiesMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMaximal Tolerated DoseMaximally Tolerated DoseMaximum Tolerated DoseMeasuresMetabolicMetabolic ProcessesMetabolismMethodsMethyl AldehydeMiceMice MammalsModelingMolecular BiologyMurineMusMutagensMutateNormal TissueNormal tissue morphologyOnco-Suppressor GenesOncogenes-Tumor SuppressorsOvarianOvary CancerOxomethaneOxygen RadicalsPatientsPb elementPharmacodynamicsPharmacokineticsPlayPoisonPre-Clinical ModelPreclinical ModelsPro-OxidantsPropertyPteroylglutamic AcidRNF53Reactive Oxygen SpeciesRecessive OncogenesResearchRoleStrains Cell LinesTechniquesTestingTetrahydrofolatesTherapeuticToxic ChemicalToxic SubstanceToxic effectToxicitiesToxinTreatment EfficacyTumor Suppressing GenesTumor Suppressor GenesUnscheduled DNA SynthesisVIT CVitamin CVitamin MVitaminsWeight LossWeight Reductionanalyze DNAanti-cancer therapyanticancer activitybody weight lossbrca 1 genebrca 2 genebrca genecancer cellcancer cell metabolismcancer metabolismcancer therapycancer-directed therapycell biologycell killingcheck point immunotherapycheck point inhibitor therapycheck point inhibitory therapycheck point therapycheckpoint immunotherapycheckpoint inhibitor therapycheckpoint inhibitory therapycheckpoint therapyclinical validationcrosslinkcultured cell linecytotoxiccytotoxicitydamage to kidneydetermine efficacyefficacy analysisefficacy assessmentefficacy determinationefficacy evaluationefficacy examinationefficacy studyevaluate efficacyexamine efficacygenotoxic agentheavy metal Pbheavy metal leadimmune check point therapyimmune checkpoint therapyin vivoindividuals with breast cancerinfrared microscopyintervention efficacykidney damagekidney dysfunctionmalignancymalignant breast tumormanual therapymetabolism measurementmetabolomicsmetabonomicsmutantmutations in BRCAneoplasm/cancernew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapeutic targetnew therapy approachesnew therapy targetnew treatment approachnew treatment strategynovelnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapeutic targetnovel therapy approachnovel therapy targetoncosuppressor geneovarian canceroxidationpatients with breast cancerperson with breast cancerrenalrenal damagerenal dysfunctionrepairrepairedsocial rolestandard of carestemsynergismtetrahydrofolic acidtetrahydropteroylglutamatetherapeutic efficacytherapy efficacytooltoxic compoundtreatment strategytumortumor cell metabolismtumor growthtumor metabolismvitamin Bcwt-loss
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Project Summary
BRCA1 and BRCA2 are tumor suppressor genes frequently inactivated in cancer, particularly in ovarian and
breast cancers. Despite recent advances in therapy, many patients with BRCA1/2-deficient cancers eventually
die of the disease and, therefore, new treatment options are needed. The goal of this proposal is to develop a
novel…
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