grant
Pharmacodynamically directed targeted therapy for leukemia
Organization UNIVERSITY OF CINCINNATILocation CINCINNATI, UNITED STATESPosted 1 May 2025Deadline 30 Apr 2030
NIHUS FederalResearch GrantFY20255-Azadeoxycytidine5-deoxyazacytidineAML - Acute Myeloid LeukemiaAcute Myeloblastic LeukemiaAcute Myelocytic LeukemiaAcute Myelogenous LeukemiaAddressAdverse ExperienceAdverse eventAllogenicAntioncogene Protein p53AttentionBiological MarkersBloodBlood Precursor CellBlood Reticuloendothelial SystemCancersCell BodyCell DeathCellsCellular Tumor Antigen P53Cessation of lifeClinicClinical TrialsClinical Trials DesignDHOdehaseDNA mutationDNA seqDNA sequencingDNAseqDataDeathDecitabineDeoxyazacytidineDevelopmentDezocitidineDihydroorotate Dehydrogenase InhibitorDihydroorotate dehydrogenaseDihydroorotic Acid DehydrogenaseDiseaseDisease ProgressionDisorderDoseDrug KineticsEnzyme GeneEnzymesExtinctionFutureGenetic ChangeGenetic defectGenetic mutationHematologic CancerHematologic MalignanciesHematologic NeoplasmsHematological MalignanciesHematological NeoplasmsHematological TumorHematopoietic CancerHematopoietic Progenitor CellsHematopoietic stem cellsIFN-regulatory factor 3IRF-3 proteinIRF3IRF3 geneImmune Cell ActivationImmune mediated therapyImmunologically Directed TherapyImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunotherapyInnate Immune SystemInterferon Regulatory Factor 3KnowledgeLeadLegal patentMacrophageMalignant Hematologic NeoplasmMalignant NeoplasmsMalignant TumorMaximal Tolerated DoseMaximally Tolerated DoseMaximum Tolerated DoseMeasurementMediatingMitochondriaMonitorMutateMutationMφOhioOncoprotein p53OutcomeP53PK/PDPatentsPathway interactionsPatient outcomePatient-Centered OutcomesPatient-Focused OutcomesPatientsPb elementPerformancePhagocytosisPharmacodynamicsPharmacokineticsPhasePhase 1b/2 TrialPhase Ib/II TrialPhosphoprotein P53Phosphoprotein pp53Preclinical dataProtein TP53PublishingPyrimidineRefractoryRelapseSafetyScheduleSolid NeoplasmSolid TumorStressTP53TP53 geneTP53 mutated AMLTP53 mutated acute myeloid leukemiaTP53-mutant AMLTP53-mutant acute myeloid leukemiaTRP53TherapeuticTimeToxic effectToxicitiesTranslatingTreatment-related toxicityTumor CellTumor Protein p53Tumor Protein p53 GeneUniversitiesValidationXenograft Modelacute granulocytic leukemiaacute granulocytic leukemia cellacute myeloblastic leukemia cellacute myelocytic leukemia cellacute myelogenous leukemia cellacute myeloid leukemiaacute myeloid leukemia cellacute nonlymphocytic leukemia celladult leukemiabio-markersbiologic markerbiomarkerblood cell progenitorblood progenitorblood stem cellblood-forming stem cellchemotherapyclinical candidatedesigndesigningdetermine efficacydevelopmentaldihydro-orotate dehydrogenasedihydroorotatedisease subgroupsdisease subtypedisorder subtypedrug developmentefficacy analysisefficacy assessmentefficacy determinationefficacy evaluationefficacy examinationevaluate efficacyexamine efficacyexpression subtypesfirst in manfirst-in-humangenome mutationheavy metal Pbheavy metal leadhematopoietic progenitorhematopoietic stem progenitor cellhemopoietic progenitorhemopoietic stem cellimmune activationimmune suppressionimmune suppressive activityimmune suppressive functionimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapiesimmune-based treatmentsimmuno therapyimmunosuppressive activityimmunosuppressive functionimmunosuppressive responseimprovedin vivoin vivo Modelin vivo monitoringinnovateinnovationinnovativeleukemia treatmentleukemic therapymalignancymitochondrialmolecular sub-typesmolecular subsetsmolecular subtypesnecrocytosisneoplasm/cancerneoplastic cellnovelp53 Antigenp53 Genesp53 Tumor Suppressorpathwaypatient oriented outcomespharmacodynamic biomarkerpharmacodynamic markerpharmacokinetics and pharmacodynamicspharmacologicphase 1 evaluationphase 1 testingphase 1 trialphase 2 studyphase I evaluationphase I testingphase I trialphase II studypre-clinicalpre-clinical developmentpreclinicalpreclinical developmentpreclinical findingspreclinical informationprogenitor cell based therapyprogenitor cell therapyprogenitor cell treatmentprogenitor therapyprogenitor treatmentprogramsprotein p53relapse patientsresponsesmall moleculestem and progenitor cell therapystem cell based therapystem cell mediated therapystem cell therapeuticsstem cell therapystem cell treatmentstem cell-based therapeuticstem cell-based treatmentsynergismtargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic targettherapeutic toxicitytherapeutically effectivetherapy associated toxicitytherapy related toxicitytherapy toxicitytreatment toxicitytreatment-associated toxicitytumorvalidationsxenograft transplant modelxenotransplant model
Description preview
PROJECT SUMMARY
Acute Myeloid Leukemia (AML) is both the most common and deadliest adult leukemia. Even with the best
therapeutic approaches the majority of AML patients relapse and die of their disease. Our central hypothesis is
that the inability to therapeutically impact AML outcome is derived from the similarity of these tumor cells to
normal…
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