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

摘要

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.