Microfluidic Droplet Organoids to Decipher the Tumor Heterogeneity in CRC of African Ancestry
微流控液滴类器官破译非洲血统结直肠癌肿瘤异质性
基本信息
- 批准号:10355977
- 负责人:
- 金额:$ 18.82万
- 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:2022-03-01 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:AddressAfrican AmericanAfrican American populationAfrican ancestryBiologicalBiologyCancer EtiologyCancer ModelCellsCessation of lifeChemoresistanceClinicColorectalColorectal CancerDiseaseDrug resistanceEpigenetic ProcessEthnic groupFluorouracilFutureGeneral PopulationGeneticGenotypeHealth Services AccessibilityHeterogeneityIn VitroIncidenceIndividualLeadMalignant NeoplasmsMethodsMicrofluidicsMolecularOrganoidsPatient-Focused OutcomesPatientsPharmaceutical PreparationsPhenotypePopulationPre-Clinical ModelPrognosisRaceResistanceScreening for cancerSpecimenStructureTechniquesTechnologyTestingTranslatingUnited StatesWorkbasecancer cellcancer health disparitycancer therapycolon cancer patientscolorectal cancer treatmentdisease heterogeneitydrug sensitivitydrug use screeningepigenetic profilingepigenomeepigenomicsessayshigh throughput screeninghigh-throughput drug screeningimprovedimproved outcomein vivoirinotecanmicrofluidic technologyneoplastic cellnovelnovel strategiesnovel therapeutic interventionnovel therapeuticsoxaliplatinpatient responseracial and ethnicresistance mechanismresponsesingle cell sequencingstandard of caretherapy resistanttreatment responsetumortumor growthtumor heterogeneity
项目摘要
Abstract
Colorectal cancer is the third most common cancer and the third leading cause of cancer deaths in the US
and the incidence of colorectal cancer in African Americans is higher than the general population. Furthermore,
survival among African American patients with colorectal cancer remains significantly lower than other racial
groups. Therefore, colorectal cancer in African American patients still remains a debilitating disease and there
is an unmet need to further understand the biology and specifically tumor heterogeneity of this disease to develop
new therapeutic approaches for these patients in order to improve treatment and overall prognosis. In our
preliminary work, we have developed a droplet-based microfluidics based technology to generate miniature
droplet organoids (MDO) that can be used to grow single cancer cells to study tumor heterogeneity and drug
resistance. Thus, our overall hypothesis is that MDO is the only method that can be used to systematically
study tumor heterogeneity both functionally and genomically. We now propose to test our hypothesis by 1)
Generating miniature droplet organoids (MDO) from patients of African ancestry with CRC in order to perform
high-throughput drug screens to study tumor heterogeneity and 2) Systematically characterize the epigenomes
of the clonal CRC MDO populations and associate them with tumor growth heterogeneity and resistance to
therapy. In summary, these studies will take important steps toward understanding tumor heterogeneity in order
to develop and validate new and potent therapies in African American colorectal cancer patients that can be
successfully translated into the clinic.
摘要
结直肠癌是美国第三大常见癌症,也是癌症死亡的第三大原因
非裔美国人的结肠直肠癌发病率高于一般人群。此外,委员会认为,
非裔美国人结直肠癌患者的生存率仍然显著低于其他种族
组因此,非裔美国人的结直肠癌仍然是一种使人衰弱的疾病,
进一步了解这种疾病的生物学,特别是肿瘤异质性,
为这些患者提供新的治疗方法,以改善治疗和总体预后。在我们
初步工作,我们已经开发出一种基于液滴的微流体技术,
液滴类器官(MDO),可用于生长单个癌细胞,以研究肿瘤异质性和药物
阻力因此,我们的总体假设是,MDO是唯一可以用来系统地
从功能和基因组两方面研究肿瘤异质性。我们现在建议通过1)来检验我们的假设。
从具有CRC的非洲血统的患者中产生微型液滴类器官(MDO),以便执行
高通量药物筛选以研究肿瘤异质性和2)系统地表征表观基因组
的克隆CRC MDO人群,并将其与肿瘤生长异质性和耐药
疗法总之,这些研究将为理解肿瘤异质性迈出重要的一步,
在非裔美国人结直肠癌患者中开发和验证新的有效疗法,
成功地转化为临床。
项目成果
期刊论文数量(0)
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SHIAOWEN David HSU其他文献
SHIAOWEN David HSU的其他文献
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{{ truncateString('SHIAOWEN David HSU', 18)}}的其他基金
Microfluidic Droplet Organoids to Decipher the Tumor Heterogeneity in CRC of African Ancestry
微流控液滴类器官破译非洲血统结直肠癌肿瘤异质性
- 批准号:
10573300 - 财政年份:2022
- 资助金额:
$ 18.82万 - 项目类别:
Epigenomic Reprogramming in Patient Derived Models of Colorectal Cancer
患者衍生的结直肠癌模型中的表观基因组重编程
- 批准号:
10241490 - 财政年份:2018
- 资助金额:
$ 18.82万 - 项目类别:
Epigenomic Reprogramming in Patient Derived Models of Colorectal Cancer
患者衍生的结直肠癌模型中的表观基因组重编程
- 批准号:
10458068 - 财政年份:2018
- 资助金额:
$ 18.82万 - 项目类别:
Epigenomic Reprogramming in Patient Derived Models of Colorectal Cancer
患者衍生的结直肠癌模型中的表观基因组重编程
- 批准号:
9978737 - 财政年份:2018
- 资助金额:
$ 18.82万 - 项目类别:
Epigenomic Reprogramming in Patient Derived Models of Colorectal Cancer
患者衍生的结直肠癌模型中的表观基因组重编程
- 批准号:
9767743 - 财政年份:2018
- 资助金额:
$ 18.82万 - 项目类别:
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