Biologic Factors in Triple-Negative Breast Cancer Health Disparities
Biologic Factors in Triple-Negative Breast Cancer Health Disparities
批准号:
9152251
负责人:
Richard Joseph Pietras
金额:
$12.41万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
AccountingAddressAfrican AmericanAgonistAmphiregulinApoptosisAreaBiological FactorsBiological MarkersBiopsy SpecimenBreast Cancer CellBreast Cancer cell lineCancer BiologyCancer BurdenCancer CenterCancer PrognosisCaucasiansCell LineCell ProliferationCellsCessation of lifeClinicClinicalClinical TrialsCollectionDataDiseaseERBB2 geneEndocrineEstrogen Receptor alphaEstrogen Receptor betaEstrogen ReceptorsEthnic OriginEthnic groupExhibitsFacultyFutureGenesGoalsGrowthHispanicsHormonesHumanImmunodeficient MouseImplantIn VitroIndividualInsulin-Like Growth Factor IILaboratoriesLigand BindingLigandsLinkMalignant NeoplasmsMedical StudentsMentorsMessenger RNAMetabolicMolecularNeoplasm MetastasisNude MiceOutcomePDCD1LG1 genePathologicPathway interactionsPatientsPhenotypePre-Clinical ModelProgesterone ReceptorsProtein IsoformsRaceReceptor GeneRelapseReportingResearchResearch PriorityResearch TrainingRiskRoleSignal PathwaySignal TransductionSomatotropinSpecimenTissue MicroarrayTranslatingTumor PromotionUnderserved PopulationVascular Endothelial Growth FactorsWomanWorkXenograft procedureanticancer activityanticancer researchbasebreast cancer survivalcancer health disparitycareer developmentcaucasian Americancell behaviorchemotherapydisorder subtypeethnic minority populationexperiencegene productin vivoinnovationmRNA Expressionmalignant breast neoplasmmigrationmortalitymouse modelnew therapeutic targetnovelprognosticprogramsracial and ethnictargeted treatmenttherapeutic targettissue biomarkerstooltranslational approachtriple-negative invasive breast carcinomatumor progressionvectoryoung woman
中文摘要
项目总结
英文摘要
Project Summary
Triple-negative breast cancers (TNBC) occur in 10-15% of patients, yet this disease subtype accounts for
almost half of all breast cancer deaths. TNBCs lack clinical expression of estrogen receptor (ER)-alpha,
progesterone receptor and HER-2 and cannot be treated with current endocrine or HER2-targeted therapies.
TNBCs are heterogeneous and occur often in African American and younger women. Although initially
responsive to some chemotherapies, TNBCs tend to relapse and metastasize early, leading to poor clinical
outcome. Our highest priority is to define new therapeutic targets that can be translated to the clinic. We
predict that expression of a second ER gene product, termed ER-beta, may be such a target in all or subsets
of TNBCs. In preliminary work with TNBC biopsy specimens from African American and Caucasian women, we
find ER-beta1 expression correlates with significantly worse 5-year overall survival in patients treated with
chemotherapy and with shorter disease-free intervals. Further, a panel of TNBC cell lines all exhibit significant
ER-beta expression, with relatively higher levels detected in cells from African Americans. Other reports also
find ER-beta associates with more aggressive phenotypes in breast cancer, particularly in African Americans.
Thus, we hypothesize that ER-beta occurs in most TNBCs and modulates tumor progression. In addition,
preliminary data show that insulin-like growth factor-2 (IGF-2), known to associate with tumor promotion, is
also expressed in TNBC specimens and stimulates high expression of ER-beta mRNA to promote TNBC
progression. Growth-stimulating effects of this pathway may be due in part to downstream actions to promote
VEGF, amphiregulin and Wnt-10b activity. Aims of this project are to: 1) use tissue microarrays (TMA) to
assess expression of ER-beta forms and IGF-2 as well as clinical consequences of expression in individuals of
diverse race/ethnicity with TNBC; 2) assess effects of ER-beta on cell proliferation, apoptosis and signaling
interactions with growth factors (IGF-2) and PD-L1 in TNBC cells in vitro; 3) determine activity of available ER-
beta agonists and antagonists on progression of human TNBC implants in immunodeficient mice in vivo. This
work may help address the unequal burdens of cancer among racial/ethnic minorities and underserved groups
represented in the TNBC-TMA and assess the interplay of these factors with cancer biology—namely
expression and activity of important hormone/growth factor signaling pathways in patients afflicted with TNBC.
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会议论文
Development of New Therapeutics for Pancreatic Cancer Management
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批准号:8490000
-
项目类别:
-
资助金额:$16.75万
-
财政年份:2013
-
负责人:Richard Joseph Pietras
-
依托单位:
(2/2) CDU/UCLA Cancer Center Partnership to Eliminate Cancer Health Disparities
-
批准号:10247107
-
项目类别:
-
资助金额:$34.5万
-
财政年份:2009
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负责人:Richard Joseph Pietras
-
依托单位:
NEW ENDOCRINE THERAPY IN OLDER WOMEN WITH BREAST CANCER
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批准号:2395145
-
项目类别:
-
资助金额:$11.65万
-
财政年份:1997
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负责人:Richard Joseph Pietras
-
依托单位:
NEW ENDOCRINE THERAPY IN OLDER WOMEN WITH BREAST CANCER
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批准号:2732623
-
项目类别:
-
资助金额:$16.39万
-
财政年份:1997
-
负责人:Richard Joseph Pietras
-
依托单位:
NEW ENDOCRINE THERAPY IN OLDER WOMEN WITH BREAST CANCER
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批准号:6029836
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项目类别:
-
资助金额:$16.7万
-
财政年份:1997
-
负责人:Richard Joseph Pietras
-
依托单位:
GROWTH FACTOR RECEPTOR DIRECTED THERAPY IN CANCER
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批准号:2101602
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项目类别:
-
资助金额:$10.43万
-
财政年份:1995
-
负责人:Richard Joseph Pietras
-
依托单位:
GROWTH FACTOR RECEPTOR DIRECTED THERAPY IN CANCER
-
批准号:2101603
-
项目类别:
-
资助金额:$10.43万
-
财政年份:1995
-
负责人:Richard Joseph Pietras
-
依托单位:
GROWTH FACTOR RECEPTOR DIRECTED THERAPY IN CANCER
-
批准号:2654120
-
项目类别:
-
资助金额:$10.43万
-
财政年份:1995
-
负责人:Richard Joseph Pietras
-
依托单位:
GROWTH FACTOR RECEPTOR DIRECTED THERAPY IN CANCER
-
批准号:2330846
-
项目类别:
-
资助金额:$10.43万
-
财政年份:1995
-
负责人:Richard Joseph Pietras
-
依托单位:
GROWTH FACTOR RECEPTOR DIRECTED THERAPY IN CANCER
-
批准号:2871803
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项目类别:
-
资助金额:$10.43万
-
财政年份:1995
-
负责人:Richard Joseph Pietras
-
依托单位:
海外基金