Project 1: Increasing therapeutic efficacy in isocitrate dehydrongenase (IDH)–mutant acute myeloid leukemia (AML)
Project 1: Increasing therapeutic efficacy in isocitrate dehydrongenase (IDH)–mutant acute myeloid leukemia (AML)
批准号:
10474275
负责人:
Ross L Levine
金额:
$36.77万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-08-24 至 2026-06-30
关键词:
Acute Myelocytic LeukemiaAllelesBiological AssayChemotherapy-Oncologic ProcedureClinicalClinical ResearchClinical TrialsCombined Modality TherapyCore FacilityCoupledDevelopmentDiseaseDoseEnrollmentFLT3 geneFLT3 inhibitorGenesGenetic studyGenomicsGenotypeGoalsIn complete remissionInvestigationIsocitratesLeadMemorial Sloan-Kettering Cancer CenterModelingMolecularMutateMutationPathogenesisPathway interactionsPatientsRecurrenceRefractoryRelapseResearch Project GrantsResistanceRoleSamplingScienceSignal TransductionTestingTherapeuticTherapeutic TrialsTreatment EfficacyValidationbaseimproved outcomeinhibitorinhibitor therapyinsightleukemiamouse modelmutantnovelnovel therapeutic interventionnovel therapeuticspatient subsetspre-clinicalpreclinical studypreventprogramsrelapse patientsresistance mechanismresponsesmall moleculetargeted treatmenttherapy resistant
中文摘要
摘要
英文摘要
ABSTRACT
We and others have genetically and functionally characterized the contribution of recurrent somatic alterations
to acute myeloid leukemia (AML) pathogenesis, including IDH1/IDH2 mutations. This has led to novel insights
into AML pathogenesis and led to the identification and validation of IDH1/2 inhibitors as a therapeutic
approach in AML; the first small molecule IDH1 (ivosidenib) and IDH2 (enasidenib) inhibitors are now approved
for relapsed/refractory IDH1/2 mutant AML. However, not all patients respond to IDH1/2 inhibition and a subset
of patients relapse following responses to IDH inhibition. We will use preclinical studies and analysis of primary
samples from patients treated with IDH1/2 inhibitors to delineate molecular predictors of sensitivity and
resistance to IDH inhibitors, and to test new combination therapeutic approaches to increase therapeutic
efficacy in IDH1/2-mutant AML. This will include mechanism-based clinical trials in genetically defined subsets,
including a novel, mechanism-based clinical trial combining FLT3 and IDH1/2 inhibition in patients with
concurrent mutations. Project 1 will interact with all 3 other Leukemia SPORE research projects and will utilize
all core facilities in this program. Our collaborative efforts will include genomic interrogation of patient samples,
preclinical therapeutic and mechanistic studies, and clinical trials with extensive correlative science aimed to
nominate the best combination therapeutic approaches for AML patients with IDH1/2 mutations.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Assessing the Interplay Between Inflammatory Signaling and Epigenetic Dysregulation in Age-associated Clonal Hematopoiesis and Leukemia Initiation
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批准号:10291637
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项目类别:
-
资助金额:$53.8万
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财政年份:2021
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负责人:Ross L Levine
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依托单位:
Assessing the Interplay Between Inflammatory Signaling and Epigenetic Dysregulation in Age-associated Clonal Hematopoiesis and Leukemia Initiation
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批准号:10659254
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项目类别:
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资助金额:$51.55万
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财政年份:2021
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负责人:Ross L Levine
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依托单位:
Assessing the Interplay Between Inflammatory Signaling and Epigenetic Dysregulation in Age-associated Clonal Hematopoiesis and Leukemia Initiation
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批准号:10488271
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项目类别:
-
资助金额:$51.81万
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财政年份:2021
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负责人:Ross L Levine
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依托单位:
Developmental Research Program
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批准号:10474305
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项目类别:
-
资助金额:$7.33万
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财政年份:2021
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负责人:Ross L Levine
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依托单位:
Synergistic role of signaling and epigenetics in leukemic transformation
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批准号:10323022
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项目类别:
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资助金额:$105.6万
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财政年份:2017
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负责人:Ross L Levine
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依托单位:
Synergistic role of signaling and epigenetics in leukemic transformation
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批准号:10543794
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项目类别:
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资助金额:$105.6万
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财政年份:2017
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负责人:Ross L Levine
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依托单位:
Synergistic role of signaling and epigenetics in leukemic transformation
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批准号:10737736
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项目类别:
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资助金额:$106.2万
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财政年份:2017
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负责人:Ross L Levine
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依托单位:
Synergistic role of signaling and epigenetics in leukemic transformation
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批准号:10078940
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项目类别:
-
资助金额:$107.76万
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财政年份:2017
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负责人:Ross L Levine
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依托单位:
ECOG-ACRIN INTEGRATED LEUKEMIA TRANSLATIONAL RESEARCH CENTER
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批准号:9235262
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项目类别:
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资助金额:$60.0万
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财政年份:2014
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负责人:Ross L Levine
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依托单位:
ECOG-ACRIN INTEGRATED LEUKEMIA TRANSLATIONAL RESEARCH CENTER
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批准号:8605643
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项目类别:
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资助金额:$60.0万
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财政年份:2014
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负责人:Ross L Levine
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依托单位:
ECOG-ACRIN INTEGRATED LEUKEMIA TRANSLATIONAL RESEARCH CENTER
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批准号:9031084
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项目类别:
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资助金额:$60.0万
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财政年份:2014
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负责人:Ross L Levine
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依托单位:
Molecular Pathogenesis and Therapy of ET and PMF
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批准号:9185463
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项目类别:
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资助金额:$40.71万
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财政年份:2010
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负责人:Ross L Levine
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依托单位:
Molecular Pathogenesis and Therapy of ET and PMF
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批准号:8403844
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项目类别:
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资助金额:$40.63万
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财政年份:2010
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负责人:Ross L Levine
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依托单位:
Molecular Pathogenesis and Therapy of ET and PMF
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批准号:8208241
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项目类别:
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资助金额:$43.23万
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财政年份:2010
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负责人:Ross L Levine
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依托单位:
Molecular Pathogenesis and Therapy of ET and PMF
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批准号:8586237
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项目类别:
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资助金额:$41.93万
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财政年份:2010
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负责人:Ross L Levine
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依托单位:
Molecular Pathogenesis and Therapy of ET and PMF
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批准号:8097381
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项目类别:
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资助金额:$43.23万
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财政年份:2010
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负责人:Ross L Levine
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依托单位:
Dynamics of Tumor Stem Cells in Cancer Initiation, Therapy, and Resistance
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批准号:8119712
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项目类别:
-
资助金额:$48.73万
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财政年份:2008
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负责人:Ross L Levine
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依托单位:
High Throughput Screen for JAK2V617F Mutant Selective Inhibitors
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批准号:7522193
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项目类别:
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资助金额:$2.5万
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财政年份:2008
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负责人:Ross L Levine
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依托单位:
Dynamics of Tumor Stem Cells in Cancer Initiation, Therapy, and Resistance
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批准号:8326199
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项目类别:
-
资助金额:$47.5万
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财政年份:2008
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负责人:Ross L Levine
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依托单位:
Dynamics of Tumor Stem Cells in Cancer Initiation, Therapy, and Resistance
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批准号:7691280
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项目类别:
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资助金额:$51.4万
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财政年份:2008
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负责人:Ross L Levine
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依托单位:
海外基金