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The Heterogeneity of Glioblastoma Multiforme and its Applications towards the Dev

多形性胶质母细胞瘤的异质性及其在开发中的应用

基本信息

批准号：
8324027
负责人：
PAUL S MISCHEL
金额：
$ 36.48万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8324027
关键词：
Address Apoptosis Award Binding Biological Biological Assay Biology CCNE1 gene Cancer Center Cancer Patient Cells Chemicals Clinic Clinical Clinical Trials Companions Complement DNA DNA amplification DNA copy number Data Set Diagnostic Epidermal Growth Factor Receptor Epigenetic Process Foundations Funding Genes Genetic Genome Genomics Glioblastoma Goals Grant Heterogeneity In Vitro Individual Information Theory Intracellular Signaling Proteins Knowledge Libraries Link Malignant Neoplasms Measurement Measures Mediating Methodology Microfluidics Modeling Molecular Molecular Analysis Mus Mutate Mutation Operating Rooms Outcome PTEN gene Paraffin Embedding Pathology Pathway interactions Patients Pharmaceutical Preparations Population Population Heterogeneity Property Proteins Proteomics RNA Research Infrastructure Research Personnel Resistance Sampling Sequence Analysis Series Signal Transduction Signaling Protein Solid Solid Neoplasm Stromal Cells Surface Systems Biology Technology Testing Therapeutic Tumorigenicity Work base cancer cell cell motility cell type clinical application clinical care clinically relevant commercialization design effective therapy experience extracellular improved laser capture microdissection mouse model nano nanosystems neoplastic cell novel strategies oncology physical science programs research study response single cell analysis statistics technology development therapeutic development therapy resistant tool translational medicine tumor

项目摘要

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.

分子异质性是癌症患者治疗耐药性发展的核心。目前的病理学实践不足以分析肿瘤内异质群体的分子和功能特性。需要新的方法来获得和使用这些信息，以指导更有效的治疗，预测和抑制治疗耐药性，并改善结果 for patients患者with cancer癌症.项目4开发的平台将纳米、化学和微技术与生物学内容相结合，以促进直接从手术室对小肿瘤样本进行高度多重定量分子和功能测量。技术组合使我们能够对足够小的样本进行高度多路复用的生物测量，以便我们能够有效地解决实体胶质母细胞瘤内的异质性问题。该项目的胶质母细胞瘤重点允许利用研究人员的专业知识和CCNE第1-4年开发的既定基础设施。该基础设施包括访问精心表征的临床样品，强大的小鼠模型，以及在过去几年中获得的同伴赠款，为这些技术融入临床铺平了道路。该项目中的技术途径始于利用在当前CCNE资助下开发的DNA编码抗体库（DEAL）平台。我们将该平台扩展到许多新的测量类型，用于分析肿瘤分子异质性解析到单细胞水平。生物学内容使这些平台具有临床相关性，并为商业化增加了重要价值。我们的目标是开发技术和方法，提供与GBM患者临床护理相关的信息，但也应该广泛适用于其他疾病。实体瘤癌症。我们组建了一支高度跨学科、互动的团队，拥有多年的合作经验。我们的团队从物理科学实验室到肿瘤学诊所。