Metabolomic Analysis of Primary Human Meningioma and Schwannoma following Radiation Therapy: A Novel Approach to Identify Targetable Radiosensitive Pathways

放射治疗后原发性人类脑膜瘤和神经鞘瘤的代谢组学分析：识别靶向放射敏感途径的新方法

• 批准号: 10536483
• 负责人: Mark C Dougherty
• 金额: $ 6.98万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10536483
• 关键词: Acoustic Neuroma; Address; Aggressive behavior; Anatomy; Biochemical Pathway; Biological; Central Nervous System Neoplasms; Clinical; Collaborations; Dose; Excision; Freezing; Genes; Genetic; Genomics; Goals; Human; Implant; Intracranial Neoplasms; Investigation; Literature; Measures; Metabolic; Metabolic Pathway; Metabolism; Methods; Modeling; Molecular Target; Mus; Mutation; Neurilemmoma; Neurofibromatosis 2; Neurologic; Operative Surgical Procedures; Outcome; Pathway interactions; Patients; Pattern; Phenotype; Predictive Analytics; Proteins; Proteomics; Quality of life; RNA; Radiation; Radiation Dose Unit; Radiation Tolerance; Radiation therapy; Refractory; Sampling; Specimen; Techniques; Testing; Therapeutic; Tissues; Tumor Biology; Tumor Suppressor Genes; Work; Writing; Xenograft Model; Xenograft procedure; clinical decision-making; improved; improved outcome; in vivo; insight; meningioma; metabolic abnormality assessment; metabolomics; neoplastic cell; neurosurgery; new therapeutic target; novel strategies; novel therapeutics; prognostication; radiation effect; response; stable isotope; targeted treatment; therapeutic target; transcriptomics; tumor; tumor growth; tumor xenograft

Abstract Together, meningiomas and schwannomas account for approximately 45% of all primary intracranial neoplasms. In most cases, these tumors can be treated with surgical resection and/or radiation with good outcomes. However, when those treatments fail no further options exist. Metabolomics is the study of metabolic networks, which are critical for tissue phenotype and function and represent a common downstream pathway from genes, RNA, and proteins. Few efforts have been made to characterize the metabolomics of most central nervous system (CNS) neoplasms, including meningiomas and schwannomas. Doing so can provide insight into novel therapeutic targets. The objective of the proposed work is to leverage our access to many primary human tumor specimens to characterize their metabolomic profiles before and after radiation. We hypothesize that 1) radiation induces specific metabolomic changes in meningiomas and schwannomas, and 2) these changes arise from alterations in targetable metabolic pathways. Results from these studies will facilitate our long-term goal to identify key metabolic pathways in meningiomas and schwannomas that can be therapeutically targeted to limit tumor growth and increase the efficacy of radiotherapy. Doing so could dramatically improve both the duration and quality of life in some of our most difficult patients.

摘要 脑膜瘤和神经鞘瘤合在一起约占所有原发性颅内肿瘤的45%。 肿瘤。在大多数情况下，这些肿瘤可以通过手术切除和/或放射治疗， 结果。然而，当这些治疗失败时，没有其他选择。代谢组学是研究 代谢网络，这是至关重要的组织表型和功能，并代表了一个共同的下游 从基因、RNA和蛋白质的途径。很少有人努力描述代谢组学的特征， 大多数中枢神经系统肿瘤，包括脑膜瘤和神经鞘瘤。这样做可以 提供对新的治疗靶点的深入了解。拟议工作的目标是利用我们的访问， 许多原发性人类肿瘤标本，以表征其辐射前后的代谢组学谱。 我们假设：1）放射诱导脑膜瘤和神经鞘瘤的特定代谢组学变化， 和2）这些变化源于靶向代谢途径的改变。这些研究的结果将 促进我们的长期目标，以确定脑膜瘤和神经鞘瘤中的关键代谢途径， 治疗靶向限制肿瘤生长和增加放射治疗的功效。这样做可能 显着改善我们一些最困难的患者的生存时间和生活质量。