Subpopulations of Pancreatic Cancer Cells Defined by Glycan Markers

由聚糖标记定义的胰腺癌细胞亚群

• 批准号: 9918274
• 负责人: Randall Brand
• 金额: $ 67.17万
• 依托单位: VAN ANDEL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-18 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9918274
• 关键词: Behavior; Biological Markers; Biological Models; Cancer Research Project; Cells; Cessation of life; Characteristics; Clinical; Clinical assessments; Detection; Development; Disease; Disease Progression; Effectiveness; Evaluation; Fine needle aspiration biopsy; Fred Hutchinson Cancer Research Center; Goals; Heterogeneity; Image; Immunofluorescence Immunologic; Individual; Laboratories; Location; Malignant Neoplasms; Malignant neoplasm of pancreas; Medical; Medical center; Metastatic Neoplasm to the Liver; Methods; Modeling; Molecular; Monitor; Morphology; Nature; Operative Surgical Procedures; Organoids; Outcome; Patients; Pharmaceutical Preparations; Polysaccharides; Positioning Attribute; Primary Neoplasm; Research; Research Institute; Research Personnel; Resistance; Resources; Sampling; Serum; South Carolina; Specimen; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stress; System; Technology; Testing; Time; Universities; Xenograft procedure; behavior test; cancer cell; cancer cell subtype; candidate marker; clinical decision-making; companion diagnostics; drug development; effective therapy; lymph nodes; molecular marker; new technology; pancreatic cancer cells; research clinical testing; success; targeted treatment; tissue resource; tumor

PROJECT SUMMARY A difficulty in the development of effective treatments against pancreatic cancer is heterogeneity within and between tumors; a subset of cancer cells, rather than all cells in a tumor, is responsible for the behaviors of invasiveness and resistance to death. Drugs that act on the aggressive subpopulations promise to be more effective than drugs that act on the bulk of a tumor, but research to identify such drugs is hampered by the lack of biomarkers to detect, isolate, and study the aggressive subpopulations. The goal of this project is to identify biomarkers of aggressive subpopulations of pancreatic cancer cells. We hypothesize that distinct subtypes of pancreatic cancer cells exist, and that they differ in their invasiveness and resistance to death. We found support for this hypothesis in previous research through the identification of glycan biomarkers of subpopulations of cancer cells with differences in molecular characteristics and behaviors. We will build on the previous results to fully test the possibility that specific glycan markers can be used for detecting subtypes of cancer cells. We posit that aggressive subtypes will be associated with poor outcomes, and that they will display high invasiveness and resistance to death in model systems. To enable a complete evaluation of the candidate markers, we will employ valuable tissue resources such as primary tumors, patient-derived xenografts, and tumor organoids, and we will apply unique and powerful experimental systems—multimarker immunofluorescence and MALDI glycan imaging. Biomarkers that identify the aggressive subtypes of pancreatic cancer cells could pave the way for the development of truly effective therapies. They would provide a way to determine which model systems, or which cells within the models, are the important ones to target, and they would provide companion diagnostics to guide and monitor the use of the targeted therapies. Drugs arising from such research would, for the first time, strike at the critical point—the subset of cells giving rise to the lethal nature of the disease. We are in a good position to produce significant results given the leads from previous research, our technologies and resources, and the team of clinical, technological, and statistical experts.

项目摘要 开发针对胰腺癌的有效治疗的困难是胰腺癌内的异质性， 肿瘤之间;癌细胞的一个子集，而不是肿瘤中的所有细胞，负责肿瘤的行为。 入侵性和对死亡的抵抗力。作用于攻击性亚群的药物承诺会更加有效， 比作用于大部分肿瘤的药物更有效，但鉴定此类药物的研究受到缺乏 生物标志物来检测，隔离和研究侵略性亚群。 该项目的目标是确定胰腺癌侵袭性亚群的生物标志物 细胞我们假设胰腺癌细胞存在不同的亚型，并且它们在其分化过程中存在差异。 入侵性和对死亡的抵抗力。我们在以前的研究中发现了对这一假设的支持， 鉴定具有分子差异的癌细胞亚群的聚糖生物标志物 特点和行为。我们将建立在以前的结果，以充分测试的可能性，具体 聚糖标记物可用于检测癌细胞的亚型。我们认为，侵略性亚型将 与不良结局相关，并且它们将在模型中显示出高侵袭性和对死亡的抵抗力， 系统.为了能够对候选标记物进行全面评估，我们将使用有价值的组织资源 如原发性肿瘤，患者来源的异种移植物和肿瘤类器官，我们将应用独特的， 强大的实验系统-多标记免疫荧光和MALDI聚糖成像。 识别胰腺癌细胞侵袭性亚型的生物标志物可以为胰腺癌的治疗铺平道路。 开发真正有效的治疗方法。它们将提供一种方法来确定哪些模型系统，或 模型中的哪些细胞是重要的目标，它们将提供伴随诊断 以指导和监测靶向治疗的使用。首先，从这种研究中产生的药物 时间，打击关键点-引起疾病致命性的细胞亚群。我们处在一个 鉴于以前的研究、我们的技术和 资源，以及临床、技术和统计专家团队。