P1 - Intersection of Estrogen Receptor Signaling & EGF Receptor
P1 - Intersection of Estrogen Receptor Signaling & EGF Receptor
批准号:
7843710
负责人:
Jill M Siegfried
金额:
$27.47万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-05-12 至 2011-04-30
关键词:
A549AdenocarcinomaAgeAnimalsAntibodiesAreaAromataseAromatase InhibitorsCancer PatientCancer cell lineCell LineCell NucleusCell ProliferationCellsCharacteristicsClinicalClinical TrialsCollaborationsCombined Modality TherapyCytoplasmDataData AnalysesDevelopmentDiagnosisDiseaseDoctor of MedicineDoctor of PhilosophyEarly treatmentEffectivenessEnrollmentEnzymesEpidemiologic StudiesEpidermal Growth Factor ReceptorEpidermal Growth Factor Receptor Tyrosine Kinase InhibitorEpithelial CellsErlotinibEstrogen AntagonistsEstrogen Receptor alphaEstrogen Receptor betaEstrogen ReceptorsEstrogensFemaleFibroblastsFulvestrantFutureGefitinibGenomicsGrantHead and Neck CancerHead and neck structureHistologicHistologyHormonalHumanImmunohistochemistryIncidenceIndividualInstitutionInvestigationJointsKnowledgeLaboratoriesLengthLigandsLungLung NeoplasmsMalignant - descriptorMalignant neoplasm of lungMeasurableMembraneMinorityMolecular WeightMutationNon-Small-Cell Lung CarcinomaNormal tissue morphologyOutcomeParaffin EmbeddingPathway interactionsPatientsPhase I Clinical TrialsPhase II Clinical TrialsPhase III Clinical TrialsPlacebosPlayPostmenopausePre-Clinical ModelProductionProteinsPublishingReceptor ActivationReceptor SignalingReproduction sporesResearch PersonnelResearch Project GrantsResistanceRoleSex CharacteristicsSignal PathwaySignal TransductionSignaling MoleculeSmall Cell CarcinomaSmokerStagingStructure of parenchyma of lungSupportive careTestingTestosteroneTherapeuticTissuesTranslational ResearchTumor Cell LineTyrosine Kinase DomainTyrosine Kinase InhibitorUniversitiesUniversity of Pittsburgh Cancer InstituteVariantWomanWorkanastrozolebasec-erbB-1 Proto-Oncogenescancer cellcell typeclinically relevantdata sharinghead and neck cancer patientimprovedinhibitor/antagonistlung cancer preventionmalemenmutantnon-genomicnovelpre-clinicalprogramsprotein functionreceptorreceptor expressionresponsesexsmall moleculetumortumor growth
中文摘要
项目一将研究雌激素受体(ER)和表皮生长因子受体的假说
英文摘要
Project One will examine the hypothesis that estrogen receptor (ER) and epidermal growth factor receptor
(EGFR) activate proliferative signaling pathways in non-small cell lung cancer (NSCLC), and that these
signaling pathways overlap and interact. Based on results obtained in the first SPORE grant period, we
hypothesize that ER expression and signaling have functional significance in NSCLC and that co-inhibition of
ER and EGFR may show greater anti-tumor activity in NSCLC than inhibition of either pathway alone. Data
obtained in the first SPORE grant period suggest that there may be some sex differences in the ER pathway
in lung cancer, but that the ER pathway is also active in males. We will carry out this translational research
project targeting the ER and the EGFR in four specific aims: (1) Determine signaling molecules involved in
ER-EGFR pathway interactions in NSCLC cell lines; (2) Examine effectiveness of joint inhibition of the EREGFR
pathways on tumor growth compared to single therapy in NSCLC, using clinically relevant agents; (3)
Determine if aromatase, the enzyme that synthesizes estrogen, is present and functional in normal and
malignant lung cells and if an aromatase inhibitor has anti-tumor activity; and (4) Analyze ER and EGFR
pathway status in tissues obtained from NSCLC patients on clinical trials using combination therapy. Results
from these aims will demonstrate how the ER and EGFR signaling pathways interact and to what extent
ligand-dependent and ligand-independent ER signaling play a role in NSCLC proliferation. Results will also
determine whether inhibition of estrogen synthesis is a potentially effective therapeutic strategy for NSCLC.
Results will further demonstrate how responses to combined ER and EGFR targeting in a clinical trial are
related to ER and EGFR signaling pathways in patients' tumors and whether combined therapy gives
superior clinical responses compared to targeting EGFR alone. We will also determine to what extent EGFR
with mutation in the tyrosine kinase domain differs from wild type EGFR in the integration of the ER and
EGFR pathways. Completion of these aims will provide a new paradigm for treatments targeting the ER in
NSCLC that could be applied to both men and women with this disease.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Role of hormone pathways in chemoprevention for high risk smokers
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批准号:9117501
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项目类别:
-
资助金额:$16.98万
-
财政年份:2015
-
负责人:Jill M Siegfried
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依托单位:
P1 - Intersection of Estrogen Receptor Signaling and EGF Receptor
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批准号:8092830
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项目类别:
-
资助金额:$27.47万
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财政年份:2010
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负责人:Jill M Siegfried
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依托单位:
SPORE in Lung Cancer
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批准号:7914675
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项目类别:
-
资助金额:$37.93万
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财政年份:2009
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负责人:Jill M Siegfried
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依托单位:
ADMINISTRATIVE CORE
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批准号:7088500
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项目类别:
-
资助金额:$11.18万
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财政年份:2006
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负责人:Jill M Siegfried
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依托单位:
INTERSECTION OF ESTROGEN RECEPTOR SIGNALING AND EPIDERMAL GROWTH FACTOR RECEPTOR
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批准号:7088489
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项目类别:
-
资助金额:$17.68万
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财政年份:2006
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负责人:Jill M Siegfried
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依托单位:
Therapeutic Mechanisms of Co-Targeting of EGFR and Src Family Kinases
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批准号:8541589
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项目类别:
-
资助金额:$26.94万
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财政年份:2004
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负责人:Jill M Siegfried
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依托单位:
Therapeutic Mechanisms of Co-Targeting of EGFR and Src Family Kinases
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批准号:7893352
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项目类别:
-
资助金额:$20.85万
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财政年份:2004
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负责人:Jill M Siegfried
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依托单位:
TARGETING EGFR AND GPCR SIGNALING IN SCCHN
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批准号:6990399
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项目类别:
-
资助金额:$20.54万
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财政年份:2004
-
负责人:Jill M Siegfried
-
依托单位:
Therapeutic Mechanisms of Co-Targeting of EGFR and Src Family Kinases
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批准号:8380699
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项目类别:
-
资助金额:$17.98万
-
财政年份:2004
-
负责人:Jill M Siegfried
-
依托单位:
Therapeutic Mechanisms of Co-Targeting of EGFR and Src Family Kinases
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批准号:8322147
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项目类别:
-
资助金额:$18.5万
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财政年份:2004
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负责人:Jill M Siegfried
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依托单位:
SPORE in Lung Cancer
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批准号:6514963
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项目类别:
-
资助金额:$257.98万
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财政年份:2001
-
负责人:Jill M Siegfried
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依托单位:
SPORE in Lung Cancer
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批准号:7843720
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项目类别:
-
资助金额:$215.63万
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财政年份:2001
-
负责人:Jill M Siegfried
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依托单位:
SPORE in Lung Cancer
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批准号:8334020
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项目类别:
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资助金额:$230.0万
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财政年份:2001
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负责人:Jill M Siegfried
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依托单位:
SPORE in Lung Cancer
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批准号:7078476
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项目类别:
-
资助金额:$222.07万
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财政年份:2001
-
负责人:Jill M Siegfried
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依托单位:
SPORE in Lung Cancer
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批准号:7495841
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项目类别:
-
资助金额:$2.6万
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财政年份:2001
-
负责人:Jill M Siegfried
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依托单位:
SPORE in Lung Cancer
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批准号:6759248
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项目类别:
-
资助金额:$242.89万
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财政年份:2001
-
负责人:Jill M Siegfried
-
依托单位:
SPORE in Lung Cancer
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批准号:7287654
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项目类别:
-
资助金额:$12.5万
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财政年份:2001
-
负责人:Jill M Siegfried
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依托单位:
SPORE in Lung Cancer
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批准号:7641494
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项目类别:
-
资助金额:$0.51万
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财政年份:2001
-
负责人:Jill M Siegfried
-
依托单位:
SPORE in Lung Cancer
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批准号:6643542
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项目类别:
-
资助金额:$251.61万
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财政年份:2001
-
负责人:Jill M Siegfried
-
依托单位:
SPORE in Lung Cancer
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批准号:6911700
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项目类别:
-
资助金额:$225.58万
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财政年份:2001
-
负责人:Jill M Siegfried
-
依托单位:
国内基金
海外基金
大肠癌发生机制的adenoma-adenocarcinoma pathway同serrated pathway的关系的研究
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批准号:30840003
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项目类别:专项基金项目
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资助金额:12.0万元
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批准年份:2008
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负责人:焦宇飞
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依托单位: