Subpopulations of Pancreatic Cancer Cells Defined by Glycan Markers

项目总结 开发有效的胰腺癌治疗方法的一个困难是 在肿瘤之间；癌细胞的子集，而不是肿瘤中的所有细胞，负责 侵袭性和对死亡的抵抗。作用于攻击性亚群的药物有望比 比作用于大部分肿瘤的药物更有效，但识别此类药物的研究因缺乏而受阻 用于检测、分离和研究攻击性亚群的生物标志物。 该项目的目标是确定胰腺癌侵袭性亚群的生物标记物。 细胞。我们假设存在不同亚型的胰腺癌细胞，并且它们的 侵袭性和对死亡的抵抗。我们在之前的研究中发现了对这一假设的支持， 分子差异癌细胞亚群糖链生物标记物的鉴定 特征和行为。我们将在之前结果的基础上，充分测试具体情况的可能性 糖链标记物可用于检测癌细胞的亚型。我们假设攻击性亚型将是 与不良结局相关，在模型中表现出高侵袭性和对死亡的抵抗力 系统。为了能够对候选标记进行完整的评估，我们将利用宝贵的组织资源 例如原发肿瘤、患者来源的异种移植和肿瘤有机化合物，我们将应用独特的和 强大的实验系统--多标记免疫荧光和MALDI葡聚糖成像。 识别胰腺癌细胞侵袭性亚型的生物标记物可能为 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，或者 模型中的哪些细胞是要瞄准的重要细胞，它们将提供辅助诊断 指导和监督靶向治疗的使用。这类研究产生的药物将首次 时间，打击临界点--导致这种疾病致命性的细胞亚群。我们现在身处一个 鉴于之前研究的领先地位，我们的技术和 资源，以及临床、技术和统计专家团队。

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.