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

摘要 脑膜瘤和神经鞘瘤加起来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，效果良好。 结果。然而，当这些治疗失败时，就没有进一步的选择了。代谢组学是研究 代谢网络，对组织表型和功能至关重要，并代表一个共同的下游 来自基因、RNA和蛋白质的途径。几乎没有人努力来描述新陈代谢组学的特征 大多数中枢神经系统(CNS)肿瘤，包括脑膜瘤和神经鞘瘤。这样做可以 提供对新治疗靶点的洞察。拟议工作的目标是利用我们访问 许多原发的人类肿瘤标本，以表征它们在辐射前后的代谢谱。 我们假设：1)辐射可引起脑膜瘤和神经鞘瘤特定的代谢改变， 2)这些变化是由靶向代谢途径的改变引起的。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可能存在的关键代谢途径 在治疗上有针对性地限制肿瘤生长和提高放射治疗的疗效。这样做可能会 极大地改善了我们一些最困难的患者的持续时间和生活质量。

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.