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Review
. 2024 Oct 22;15(1):577.
doi: 10.1007/s12672-024-01402-5.

Metabolism: an important player in glioma survival and development

Ning Wang #  1   2 , Yiru Yuan #  1   2 , Tianhao Hu  1   2 , Huizhe Xu  3   4 , Haozhe Piao  5   6
Affiliations
Review

Metabolism: an important player in glioma survival and development

Ning Wang et al. Discov Oncol. .

Abstract

Gliomas are malignant tumors originating from both neuroglial cells and neural stem cells. The involvement of neural stem cells contributes to the tumor's heterogeneity, affecting its metabolic features, development, and response to therapy. This review provides a brief introduction to the importance of metabolism in gliomas before systematically categorizing them into specific groups based on their histological and molecular genetic markers. Metabolism plays a critical role in glioma biology, as tumor cells rely heavily on altered metabolic pathways to support their rapid growth, survival, and progression. Dysregulated metabolic processes, involving carbohydrates, lipids, and amino acids not only fuel tumor development but also contribute to therapy resistance and metastatic potential. By understanding these metabolic changes, key intervention points, such as mutations in genes like RTK, EGFR, RAS, and IDH can be identified, paving the way for novel therapeutic strategies. This review emphasizes the connection between metabolic pathways and clinical challenges, offering actionable insights for future research and therapeutic development in gliomas.

Keywords: Gliomas; Glucose metabolism; Lipid metabolism; Metabolisms; Signaling pathway; Treatment directions.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Diagram of Interactions Between Glioma, Brain Cells, and the Blood–Brain Barrier (The illustration primarily depicts the location of glioma cells in the brain, their interactions with neurons, astrocytes, and microglia, and their acquisition of nutrients from across the blood-brain barrier.)
Fig. 2
Fig. 2
Energy metabolism in gliomas (Tumor cells often rely on aerobic glycolysis (Warburg effect), converting glucose to lactate even in the presence of oxygen to rapidly generate energy and building blocks for growth. Under hypoxic conditions, they switch to anaerobic glycolysis, breaking down glucose without oxygen. Additionally, tumor cells can use other pathways like fatty acid oxidation and pyruvate catabolism, depending on the tumor type, environment, and regulatory mechanisms.)
Fig. 3
Fig. 3
RTK signaling pathways in gliomas metabolism (The progression of gliomas is closely associated with the overexpression of RTKs and the abnormal activation of their signaling pathways. This overexpression leads to the phosphorylation of tyrosine kinases, activating downstream pathways associated with factors such as PI3K, EGF, VEGF, and PDGF. Consequently, this results in increased cell proliferation and growth, as well as reduced apoptosis, thereby facilitating tumor development.)
Fig. 4
Fig. 4
RAS/RAF/MEK/ERK signaling pathways in gliomas metabolism (Extracellular signals stimulate the proto-oncogene Ras, activating it through binding with GTP, which subsequently phosphorylates and activates Raf. Raf then activates the MEK, which through phosphorylation activates the ERK, ultimately driving gene expression. The activated ERK catalyzes the phosphorylation of numerous cytoplasmic effectors and nuclear transcription factors, thereby inducing cell survival, migration, and proliferation. Inhibiting the abnormal activation of this pathway can effectively suppress the proliferation of glioma cells and improve resistance to TMZ)
Fig. 5
Fig. 5
IDH gene mutations in gliomas metabolism (Mutations in the IDH gene, including three subtypes IDH1, IDH2, and IDH3, play a significant role in energy metabolism and biosynthesis. Current research suggests that mutations in IDH1 and IDH2 are among the critical factors in the origin of gliomas. Mutations in IDH1/2 lead to an enzymatic activity change, catalyzing the reduction of α-KG to D2-HG.)
Fig. 6
Fig. 6
TP53 gene mutations in gliomas metabolism (When DNA is damaged, the ATM and ATR proteins are activated, which then phosphorylate and activate downstream kinases CHEK1 and CHEK2, thereby halting cell cycle progression to allow time for DNA repair. Concurrently, ATM and ATR activate the tumor suppressor protein p53, which can lead to either cell cycle arrest or apoptosis. The activity and stability of p53 are negatively regulated by MDM2 and MDM4 proteins. Activated p53 can induce the expression of genes such as CDKN2A, which in turn inhibits MDM2, leading to cell cycle arrest. Additionally, p53 can activate the expression of pro-apoptotic genes like FAS, triggering cell apoptosis.)
Fig. 7
Fig. 7
Treatment options for gliomas (The image outlines the treatment regimen for gliomas based on patient age, IDH gene status, and 1p/19q co-deletion. For low-grade gliomas, surgical resection is typically preferred for younger patients, while older patients may receive a combination of radiotherapy and chemotherapy. The treatment of anaplastic gliomas takes into account the presence or absence of 1p/19q deletion and may include radiotherapy and chemotherapy. Treatment strategies for glioblastoma hinge on whether the IDH gene is of the mutant or wild type, as well as the patient’s age, to decide between Temozolomide or radiotherapy. Additionally, the choice of treatment method also considers the methylation status of the MGMT gene to tailor a more effective treatment plan
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