The Heterogeneity of Glioblastoma Multiforme and its Applications towards the Dev

分子异质性是癌症患者产生治疗耐药的核心因素。目前的病理学实践不足以分析肿瘤内不同种群的分子和功能特性。需要新的方法来获得和使用这些信息来指导更有效的治疗，以预测和抑制治疗耐药，并改善结果。 适用于癌症患者。项目4开发了将纳米、化学和微技术与生物含量相结合的平台，以促进直接从手术室对小肿瘤样本进行高度多元化的定量分子和功能测量。技术组合允许我们在足够小的样本上进行高度多元化的生物测量，这样我们就可以有效地解决 实体型胶质母细胞瘤内的异质性问题。这个项目的重点是胶质母细胞瘤，它允许利用研究人员的专业知识和在我们CCNE的1-4年间开发的已建立的基础设施。这一基础设施包括访问精心表征的临床样本、强大的鼠标 过去几年获得的模型和配套赠款，为将这些技术整合到临床铺平了道路。该项目中的技术途径首先利用在当前CCNE资金下开发的DNA编码抗体文库(Deal)平台。我们将这一平台扩展到一系列新的测量类型，用于分析肿瘤分子的异质性 解析到单细胞级别。生物含量使这些平台具有临床相关性，并为商业化增加了重大价值。我们的目标是开发提供与GBM患者临床护理相关的信息的技术和方法，但这些技术和方法也应该广泛适用于其他 实体瘤癌症。我们组建了高度跨学科、互动的团队，他们在合作方面拥有多年的经验。我们的团队从物理科学实验室连接到肿瘤学诊所。

Molecular heterogeneity is central to the development of therapeutic resistance in cancer patients. Current pathology practices are not sufficient for analyzing the molecular and functional properties of heterogeneous populations within a tumor. New approaches are needed for obtaining and using this information to guide more effective treatments that anticipate and suppress therapeutic resistance, and that improve the outcome for patients with cancer. Project 4 develops platforms combining nano-, chemical and micro-technologies with biological content to facilitate highly multiplexed quantitative molecular and functional measurements of small tumor samples directiy from the operafing room. The technology mix allows us to perform highly multiplexed biological measurements on small enough samples so that we can effectively address the questions of heterogeneity within solid glioblastoma tumors. The glioblastoma focus of this project permits leveraging the expertise of the investigators and established infrastructure developed during years 1-4 of our CCNE. This infrastructure includes access to meticulously characterized clinical samples, powerful mouse models, and companion grants obtained over the past few years that pave the way for integration of these technologies into the clinic. The technology pathway within this project begins by leveraging off of the platform of DNA encoded anfibody libraries (DEAL) that was developed under current CCNE funding. We extend this platform to a host of new measurement types for analyzing tumor molecular heterogeneity resolved to the single cell level. The biological content makes these platforms clinically relevant and adds significant value for commercialization. We aim to develop technologies and approaches that provide information relevant to the clinical care of GBM pafients, but which should also be broadly applicable to other solid tumor cancers. We have assembled highly cross-disciplinary, interactive team that has several years of experience at working together. Our team bridges from the physical science lab to the oncology clinic.