Abstract
The current standard of care for patients diagnosed with primary brain tumors consists of surgical resection, when feasible, followed by radiotherapy with concomitant and/or adjuvant chemotherapy. Unfortunately, complete surgical resection is extremely rare due to the location of these tumors and their diffuse and proliferative nature and radiation therapy can enhance the necrotic environment resulting in further tissue damage and more aggressive tumors. A common problem with chemotherapy, that limits its clinical efficacy for brain tumor treatment, is that high doses are required to circumvent drug resistance mechanisms that result in drug-related and dose-limiting toxicities. Therefore, strategies and approaches that target the mechanisms of drug resistance in brain tumors will allow dose reductions in chemotherapy while maintaining clinical efficacy and limiting drug-related toxicities. The contributions of glutathione (GSH) and the GSH-related enzymes to drug resistance in brain tumors have been largely overlooked. The major components of the GSH-related enzyme system, including glutamate cysteine ligase (GCL), glutathione synthetase (GS), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferases (GST), and GSH export transporters (GS-X pumps) are often dysregulated and promote the detoxification of various anticancer agents and confer a more drug resistant phenotype. Improving our understanding of the mechanisms of GSH-mediated drug resistance will be critical to develop targeted therapeutic approaches to chemosensitize brain tumors to treatments and to improve clinical outcomes.
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Backos, D.S., Poerschke, R.L., Franklin, C.C., Reigan, P. (2014). The Role of Glutathione and the Glutathione-Linked Enzyme Systems in Brain Tumor Drug Resistance. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 12. Tumors of the Central Nervous System, vol 12. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7217-5_24
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