Amino acid deprivation in glioblastoma: the role in survival and the tumour microenvironment—a narrative review
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Published version
Author(s)
Anichini, Giulio
Du, Keven
Grocott, Leila
O'Neill, Kevin
Syed, Nelofer
Type
Journal Article
Abstract
Background: Glioblastoma is the most common and aggressive primary brain tumour, characterised by its invasive nature and complex metabolic profile. Emerging research highlights the role of amino acids (AAs) in glioblastoma metabolism, influencing tumour growth and the surrounding microenvironment. Methods: This narrative review synthesises recent pre-clinical studies focusing on the metabolic functions of AAs in glioblastoma. Key areas include the effects of AA deprivation on tumour growth, adaptive mechanisms, and the tumour microenvironment. Results: The effects related to arginine, glutamine, methionine, and cysteine deprivation have been more extensively reported. Arginine deprivation in arginine-auxotrophic glioblastomas induces apoptosis and affects cell adhesion, while glutamine deprivation disrupts metabolic pathways and enhances autophagy. Methionine and cysteine deprivation impact lipid metabolism and ferroptosis. Tumour adaptive mechanisms present challenges, and potential compensatory responses have been identified. The response of the microenvironment to AA deprivation, including immune modulation, is critical to determining therapeutic outcomes. Conclusions: Targeting AA metabolism offers a promising approach for glioblastoma treatment, with potential targeted drugs showing clinical promise. However, the complexity of tumour adaptive mechanisms and their impact on the microenvironment necessitates further research to optimise combination therapies and improve therapeutic efficacy.
Date Issued
2024-11
Date Acceptance
2024-10-22
Citation
Biomedicines, 2024, 12 (11)
ISSN
2227-9059
Publisher
MDPI AG
Journal / Book Title
Biomedicines
Volume
12
Issue
11
Copyright Statement
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.mdpi.com/2227-9059/12/11/2481
Publication Status
Published
Article Number
2481
Date Publish Online
2024-10-29