Rapid analysis of patient tumor cell drug responses to reduce metastatic risk
快速分析患者肿瘤细胞药物反应以降低转移风险
基本信息
- 批准号:9563061
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-10-01 至 2022-09-30
- 项目状态:已结题
- 来源:
- 关键词:ActinsAffectAnimalsAntineoplastic AgentsAreaBehaviorBiomedical EngineeringBlood CirculationBlood VesselsBreast Cancer CellBreast Cancer PatientBreast Cancer TreatmentBreast Cancer cell lineBreast Cancer therapyBreast cancer metastasisCancer CenterCellsCessation of lifeCharacteristicsClinicalClinical TreatmentConfocal MicroscopyCore BiopsyDetectionDistantERBB2 geneEnsureEpithelialEpothilonesFDA approvedFemaleGrowthHealthHourImageIncidenceIndividualLaboratoriesLegal patentMagnetic Resonance ImagingMalignant NeoplasmsMammospheresMarylandMeasurementMeasuresMetastatic toMethodsMicrofluidic MicrochipsMicrofluidicsMicrotubule StabilizationMicrotubulesModelingModificationMolecularMolecular ProfilingMusNational Cancer InstituteNeoplasm Circulating CellsNeoplasm MetastasisOperative Surgical ProceduresPatient NoncompliancePatientsPharmaceutical PreparationsPharmacotherapyPhenotypePlasmaPopulationPositron-Emission TomographyPublishingRecurrenceResearch PriorityResidual stateRiskSamplingStem cellsSurfaceTailTechnologyTestingTime StudyTissuesTranslatingTranslationsTransplantationTubulinUnited StatesUniversitiesVeinsVeteransWomanWomen&aposs HealthWound HealingXenograft ModelXenograft procedureautomated image analysisbasecancer imagingcancer recurrencecancer riskcancer therapycell growthchemotherapyclinical imagingclinically relevantconfocal imagingdrug testingeffective therapyimprovedindividual patientindividual responseindividualized medicinemalignant breast neoplasmmolecular markermolecular phenotypemouse modelmultidisciplinaryneoplastic cellnew technologynoveloff-patentoptical imagingphenotypic biomarkerpressurepreventresponseresponse biomarkerrisk minimizationtaxanetissue culturetreatment strategytumortumor growthwound
项目摘要
Rapid analysis of patient tumor cell drug responses to reduce metastatic risk
Background: The current limitations of clinical cancer imaging prevent a clear understanding of how drugs
aimed at cell growth affect the metastatic potential of circulating tumor cells (CTCs) in breast cancer
patients. With more than 2.2 million female Veterans, the current incidence of breast cancer predicts that at
least 275,000 female Veterans will confront breast cancer treatment and require effective treatments that
minimize the risk of lethal metastatic spread. Recent advances in CTC analysis have shown that clusters of
breast cancer CTCs have up to 50x higher metastatic potential. The Martin lab discovered unique
microtentacles (McTNs) on the surface of breast tumor cells that increase cluster formation, and are indicative
of the elevated stem cell characteristics that promote breast cancer metastasis. Current cancer therapies that
stabilize tubulin (like taxanes and epothilones) can increase McTNs, stem cell characteristics, tumor cell
clustering, and reattachment. These results emphasize the need to clarify how current drugs affect free-floating
tumor cells so that therapies can be better tailored to individual patients and reduce long-term metastatic risk.
Objective/Hypothesis: Bringing together a multidisciplinary team of tumor cell biologists, bioengineers,
and breast cancer clinicians; the objective of this project is to use a novel microfluidic device to rapidly image
free-floating breast tumor cells and define 3 phenotypes that are predictive of metastatic potential (McTNs,
sphere formation, clustering) and key molecular markers. These phenotypes and molecular profiles will be
related to metastatic potential and drug response using clinically-relevant PDX transplants in mice. This study
will test the hypothesis that key functional phenotypes and molecular markers of freshly-isolated breast tumor
cells can serve as immediate indicators of metastatic potential and provide a platform to rapidly test the
responses of individual patient tumor cells to cancer drugs.
Specific Aims:
1) Optimize microfluidic cell tethering to measure 3 functional phenotypes of metastatic potential.
2) Establish molecular framework for tumor cell drug responses in patient-derived xenograft (PDX) cells.
3) Define shared molecular and functional characteristics of fresh patient tumor cells, PDX and CTCs.
Methods: This project will use confocal microscopy to examine 3 phenotypes (McTNs, sphere formation,
and clustering) in breast tumor cell lines and a panel of existing patient-derived xenografts (PDX) supplied by
the Translational Core Laboratory at the University of Maryland Greenebaum Cancer Center. In parallel, we
will collect fresh patient tumor samples to compare molecular markers and phenotypes in the fresh cells with
the PDX that eventually grow in mice. PDX recapitulate the metastatic behavior of the patient’s original tumor
far more faithfully than any tissue culture model. Phenotypes and molecular markers of individual patient’s
tumor cells will be compared to the molecular characteristics (ER/PR/HER2) of the original patient’s tumor, as
well as growth and metastasis in the PDX model.
Impact: The completion of this project will establish a framework for defining how the functional
phenotypes of patient tumor cells predict metastatic potential and responses to breast cancer therapies.
Current treatment strategies focus largely on inhibiting tumor growth, so this technology will open a new early
window to help ensure drug treatments avoid inadvertently increasing metastatic risk while targeting tumor
growth. Since this project will focus on FDA-approved breast cancer drugs, the findings can be more easily
translated to impact the clinical treatment of breast cancer by tailoring therapies for individual female Veterans.
快速分析患者肿瘤细胞药物反应以降低转移风险
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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STUART S MARTIN其他文献
STUART S MARTIN的其他文献
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{{ truncateString('STUART S MARTIN', 18)}}的其他基金
Rapid analysis of patient tumor cell drug responses to reduce metastatic risk
快速分析患者肿瘤细胞药物反应以降低转移风险
- 批准号:
10413064 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Rapid analysis of patient tumor cell drug responses to reduce metastatic risk
快速分析患者肿瘤细胞药物反应以降低转移风险
- 批准号:
10663790 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Rapid analysis of patient tumor cell drug responses to reduce metastatic risk
快速分析患者肿瘤细胞药物反应以降低转移风险
- 批准号:
10045933 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Targeting microtubule stabilization to reduce breast tumor metastasis
靶向微管稳定以减少乳腺肿瘤转移
- 批准号:
8540982 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Targeting microtubule stabilization to reduce breast tumor metastasis
靶向微管稳定以减少乳腺肿瘤转移
- 批准号:
8688930 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Targeting microtubule stabilization to reduce breast tumor metastasis
靶向微管稳定以减少乳腺肿瘤转移
- 批准号:
9089934 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Targeting microtubule stabilization to reduce breast tumor metastasis
靶向微管稳定以减少乳腺肿瘤转移
- 批准号:
10212975 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Targeting microtubule stabilization to reduce breast tumor metastasis
靶向微管稳定以减少乳腺肿瘤转移
- 批准号:
10437846 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Targeting microtubule stabilization to reduce breast tumor metastasis
靶向微管稳定以减少乳腺肿瘤转移
- 批准号:
10660995 - 财政年份:2012
- 资助金额:
-- - 项目类别:
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