Abstract
In 2016, the WHO introduced new guidelines for the diagnosis of brain gliomas based on new genomic markers. The addition of these new markers to the pre-existing diagnostic methods provided a new level of precision for the diagnosis of glioma and the prediction of treatment effectiveness. Yet, despite this new classification tool, glioblastoma (GBM), a grade IV glioma, continues to have one of the highest mortality rates among central nervous system tumors. Metabolomics is a particularly promising tool for the analysis of GBM tumors and potential methods of treating them, as it is the only “omics” approach that is capable of providing a metabolic signature of a tumor’s phenotype. With careful experimental design, cell cultures can be a useful matrix in GBM metabolomics, as they ensure stable conditions and, under proper conditions, are capable of capturing different tumor phenotypes. This paper reviews in vitro metabolomic profiling studies of high-grade gliomas, with a particular focus on sample-preparation techniques, crucial metabolites identified, cell culture conditions, in vitro-in vivo extrapolation, and pharmacometabolomics. Ultimately, this review aims to elucidate potential future directions for in vitro GBM metabolomics.
Highlights
Glioblastoma (GBM) is one of the most aggressive and difficult-to-treat central nervous system (CNS) brain tumors
Since 2007, the World Health Organization (WHO) has classified gliomas based on their cell type and aggressiveness, with Class I consisting of benign tumors, and Class IV comprising the most aggressive types of tumors
This review provides an overview of the major sample-preparation methods for metabolomics analysis, and analyzes promising metabolomics studies with GBM cell lines within the context of the potential biomarkers, therapeutic targets, and in vivo extrapolation (IVIVE)
Summary
Glioblastoma (GBM) is one of the most aggressive and difficult-to-treat central nervous system (CNS) brain tumors. -mtehylguanine DNA methyltransferase (MGMT), and epidermal growth factor receptors (EGFR)—thereby allowing clinicians to differentiate tumors by their cell type and aggressiveness, as was possible with pre-existing methods, and by the genetic phenotype of the neoplastic cells, providing better correlation with the tumor prognosis [2] Despite this new, improved diagnostic system, GBM continues to be the most lethal primary malignant CNS tumor. GBM tumors are difficult to treat due to their heterogeneous nature Their concentration of glioma stem-like cells (GSCs) can pose a distinct challenge, as these cells possess properties that allow them to change their cellular phenotypes in response to existing microenvironment conditions. This review provides an overview of the major sample-preparation methods for metabolomics analysis, and analyzes promising metabolomics studies with GBM cell lines within the context of the potential biomarkers, therapeutic targets, and IVIVE
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