Characterization of metastasis models derived from breast cancer patients of African descent
非洲裔乳腺癌患者转移模型的表征
基本信息
- 批准号:10669268
- 负责人:
- 金额:$ 21.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAfricanAfrican ancestryBasic ScienceBiologicalBiological ModelsBreast Cancer PatientBreast Cancer TreatmentCellsCessation of lifeClinicClinicalCollectionCommunitiesCytotoxic agentDNA MethylationDNA copy numberDataDevelopmentDiagnosisDiseaseDisparityDrug TargetingERBB2 geneEstrogen AntagonistsEstrogen ReceptorsEuropean ancestryExhibitsFeasibility StudiesGenerationsGenesGeneticGenetic Predisposition to DiseaseGenomicsGiftsGoalsGreen Fluorescent ProteinsGrowthHealthHumanIn VitroIncidenceInstitutionKnowledgeLaboratoriesLeadLuciferasesMammary NeoplasmsMethodologyMissionModelingMolecularMutationNeoplasm MetastasisOncogenesOrganOrganismOrganoidsOutcomePathway interactionsPatient-derived xenograft models of breast cancerPatientsPersonsPredispositionProgesterone ReceptorsPrognosisProteinsProtocols documentationResearchResearch DesignResourcesSusceptibility GeneSuspensionsTP53 geneTestingTherapeuticTranslatingTropismUnited StatesUnited States National Institutes of HealthVariantWomancancer health disparitycancer subtypeschemotherapeutic agentcytotoxiccytotoxicitydata acquisitionexperiencein vivo Modelinnovationinsightinterestmalignant breast neoplasmmodel developmentmortalityneoplastic cellnovel therapeuticspatient derived xenograft modelproteogenomicsresearch studyresponsestandard of caretargeted agenttherapeutic evaluationtranscriptome sequencingtriple-negative invasive breast carcinomatumor
项目摘要
Project Summary: Breast cancers arise in one out of eight women and account for ~40,000 deaths each year
in the United States. There are different types of breast tumors with varied treatment options and outcomes.
Triple-negative breast cancers (TNBC) lack estrogen and progesterone receptors (ER and PR), do not express
the HER2 oncogene, and are known to be highly metastatic. Since they lack ER, they cannot be targeted with
antiestrogens, and by not having amplified HER2, the drugs that target this protein are ineffective. People that
are of African ancestry (AA) are two-to-three times as likely to be diagnosed with basal-like TNBC than people
of European ancestry, which is a major disparity and contributes to a significantly poor prognosis. Given that
genetic factors have been identified which portend poor outcomes in AA patients, we hypothesize that AA
derived tumor cells have unique susceptibilities which can be exploited for therapeutic benefit. The goal of this
R21 project is to refine metastasis models systems derived from people of AA as they are currently lacking in
abundance and determine novel therapeutic options that may best benefit them. The proposal will (1) develop
trackable metastasis models from AA TNBC patient-derived xenografts, (2) define their organ tropism, (3)
genomically characterize them at the single-cell level, and (4) identify and test therapeutics which may be
beneficial in addition to standard of care chemotherapeutics. The study is innovative through its multifaceted
approach and significant as it will directly address a major disparity and provide options for expanded testing
of therapeutics that could be utilized in the clinic immediately. The expected outcome of these efforts is that we
will develop model systems that can be shared with the broader research community and identify genomic
features that are activated in metastases and can be targeted. Achieving these goals will have a positive impact
on disparities research and breast cancer treatment.
项目摘要:八分之一的女性患有乳腺癌,每年导致约 40,000 人死亡
在美国。乳腺肿瘤有不同类型,治疗方案和结果也各不相同。
三阴性乳腺癌 (TNBC) 缺乏雌激素和孕激素受体(ER 和 PR),不表达
HER2 癌基因,并且已知具有高度转移性。由于他们缺乏 ER,因此无法针对他们
抗雌激素药物由于没有扩增 HER2,因此针对该蛋白的药物无效。人们认为
具有非洲血统 (AA) 的人被诊断出患有基底细胞样 TNBC 的可能性是人类的两到三倍
欧洲血统,这是一个重大差异,导致预后极差。鉴于
已确定预示 AA 患者预后不良的遗传因素,我们假设 AA
衍生的肿瘤细胞具有独特的敏感性,可用于治疗益处。此举的目标
R21项目是完善源自AA人的转移模型系统,因为他们目前缺乏
并确定最有利于他们的新治疗方案。该提案将 (1) 制定
来自 AA TNBC 患者来源的异种移植物的可追踪转移模型,(2) 定义其器官向性,(3)
在单细胞水平上对它们进行基因组表征,并且(4)识别和测试可能的治疗方法
除了标准护理化疗之外还有益处。该研究通过其多方面的创新
方法非常重要,因为它将直接解决重大差异并为扩大测试提供选择
可以立即在诊所使用的治疗方法。这些努力的预期结果是我们
将开发可以与更广泛的研究界共享并识别基因组的模型系统
在转移中被激活并且可以被靶向的特征。实现这些目标将产生积极影响
关于差异研究和乳腺癌治疗。
项目成果
期刊论文数量(0)
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Joshua (Chuck) Harrell其他文献
Joshua (Chuck) Harrell的其他文献
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{{ truncateString('Joshua (Chuck) Harrell', 18)}}的其他基金
Research Project 2 Proteogenomic-guided therapeutic targeting of breast cancer patient-derived xenograft metastases
研究项目 2 蛋白质基因组引导的乳腺癌患者异种移植转移的治疗靶向
- 批准号:
10733315 - 财政年份:2023
- 资助金额:
$ 21.34万 - 项目类别:
United for Health Equity - Living PDX Program (U4HELPP)
United for Health Equity - Living PDX 计划 (U4HELPP)
- 批准号:
10733310 - 财政年份:2023
- 资助金额:
$ 21.34万 - 项目类别:
Characterization of metastasis models derived from breast cancer patients of African descent
非洲裔乳腺癌患者转移模型的表征
- 批准号:
10510244 - 财政年份:2022
- 资助金额:
$ 21.34万 - 项目类别:
Circumventing acquired carboplatin resistance in triple-negative breast cancers
规避三阴性乳腺癌的获得性卡铂耐药性
- 批准号:
10441272 - 财政年份:2020
- 资助金额:
$ 21.34万 - 项目类别:
Circumventing acquired carboplatin resistance in triple-negative breast cancers
规避三阴性乳腺癌的获得性卡铂耐药性
- 批准号:
10159229 - 财政年份:2020
- 资助金额:
$ 21.34万 - 项目类别:
Circumventing acquired carboplatin resistance in triple-negative breast cancers
规避三阴性乳腺癌的获得性卡铂耐药性
- 批准号:
10652411 - 财政年份:2020
- 资助金额:
$ 21.34万 - 项目类别:
Circumventing acquired carboplatin resistance in triple-negative breast cancers
规避三阴性乳腺癌的获得性卡铂耐药性
- 批准号:
10714928 - 财政年份:2020
- 资助金额:
$ 21.34万 - 项目类别:
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