Noninvasive Metabolic Signatures to Improve Management of Molecular Subtypes of Glioma

无创代谢特征可改善神经胶质瘤分子亚型的管理

• 批准号: 9790509
• 负责人: Susan M Chang
• 金额: $ 215.77万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9790509
• 关键词: Behavior; Biological; Biological Assay; Biological Markers; Brain; Cells; Characteristics; Clinic; Clinical; Clinical Services; Data; Data Analyses; Data Set; Development; Diagnosis; Diffusion; Disease; Evaluation; Foundations; Functional Imaging; Genes; Genomics; Geography; Glioblastoma; Glioma; Goals; Grant; Heterogeneity; Image; Imaging Techniques; Infrastructure; Lesion; Magnetic Resonance Imaging; Malignant - descriptor; Maps; Metabolic; Metabolic Marker; Metabolism; Molecular; Monitor; Multimodal Imaging; Mutation; Outcome; Patients; Perfusion; Physiological; Positioning Attribute; Pre-Clinical Model; Predictive Value; Program Research Project Grants; Property; Protocols documentation; Recurrence; Regulation; Research; Residual Tumors; Resources; Role; Sampling; Scanning; Signal Transduction; Spectrum Analysis; Subgroup; Techniques; Telomerase; Therapeutic; Tissue Sample; Translating; Tumor Biology; Tumor Burden; Tumor Markers; World Health Organization; clinical translation; clinically relevant; data acquisition; image guided; imaging biomarker; imaging modality; imaging scientist; improved; in vivo; individual patient; innovation; insight; metabolic imaging; molecular subtypes; multimodality; mutant; mutational status; neoplastic cell; neuro-oncology; neuroimaging; novel; novel imaging technology; novel therapeutics; oligodendroglioma; outcome forecast; pre-clinical; prediction algorithm; prognostic value; promoter; recruit; tool; treatment response; treatment strategy; tumor; tumor behavior

The overall goal of this P01 proposal is to improve the management of patients with different molecular subgroups of glioma, focusing on novel neuroimaging surrogates associated with metabolic and physiologic changes in each group. The delineation of histopathological and molecular subgroups of glioma has revolutionized the field of neuro-oncology by improving diagnosis and prognosis. Interrogating metabolic and physiologic signatures of these subgroups will be one of the next critical advances in the field of neuroimaging. In the previous cycle of our P01, we acquired a large dataset of image-guide tissue samples matched with MR diffusion, perfusion, and spectroscopy scans. We now seek to combine these techniques using sophisticated data analysis tools to more efficiently predict tumor burden and malignant behavior by subgroup. Our preliminary data also indicate that there are differences in metabolism associated with changes in IDH status and TERT expression that have the potential for being used in developing in vivo signatures for specific molecular subtypes. In this new proposal, we will identify multi-parametric imaging markers that are specific to each subtype; use novel gene editing tools to elucidate mechanisms that influence the regulation of mutant TERT promotor in subgroups with divergent molecular and clinical features; define metabolic signatures of TERT expression; and implement novel 1H and 13C metabolic imaging strategies for monitoring individual patients during the course of their disease. This would set the stage for developing clinical 1H and hyperpolarized 13C metabolic imaging assays that could provide early assessment of tumor recurrence and treatment response. These integrated studies will be supported by specialized resources from the Administrative and Clinical Services Core and the Biospecimen and Biomarker Core. To translate our mechanistic findings and novel imaging technologies into clinically relevant actions, we will use the unique infrastructure that our group has established over the prior cycles of this P01 to perform studies in cells, pre-clinical models, and patients. The innovative research described in this proposal will take advantage of the exceptional resources assembled by the well-established, collaborative group of clinical, biological and imaging scientists at UCSF.

该P01提案的总体目标是改善对不同分子水平患者的管理 神经胶质瘤亚组，重点关注与代谢和生理相关的新型神经影像替代物 每组的变化。神经胶质瘤的组织病理学和分子亚型的划分 通过改善诊断和预后彻底改变了神经肿瘤学领域。询问代谢和 这些亚组的生理特征将是神经影像领域的下一个关键进展之一。 在 P01 的上一个周期中，我们获取了与 MR 匹配的图像引导组织样本的大型数据集 扩散、灌注和光谱扫描。我们现在寻求使用复杂的技术将这些技术结合起来 数据分析工具可以更有效地预测亚组的肿瘤负荷和恶性行为。我们的初步 数据还表明，与 IDH 状态和 TERT 变化相关的代谢存在差异 表达有可能用于开发特定分子亚型的体内特征。 在这个新提案中，我们将确定每个亚型特有的多参数成像标记；使用 新型基因编辑工具阐明影响突变 TERT 启动子调节的机制 具有不同分子和临床特征的亚组；定义 TERT 表达的代谢特征；和 实施新的 1H 和 13C 代谢成像策略，用于在治疗过程中监测个体患者 他们的疾病。这将为开发临床 1H 和超极化 13C 代谢成像奠定基础 可以提供肿瘤复发和治疗反应的早期评估的检测。这些集成的 研究将得到行政和临床服务核心以及 生物样本和生物标志物核心。将我们的机械发现和新颖的成像技术转化为 临床相关行动，我们将使用我们小组在之前建立的独特基础设施 该 P01 的循环在细胞、临床前模型和患者中进行研究。描述的创新研究 在本提案中，将利用完善的协作性组织所汇集的特殊资源 加州大学旧金山分校的临床、生物和成像科学家小组。