Metabolic Reprogramming in Glioma: Shaping the Tumor Microenvironment and Therapeutic Resistance

Gliomas are the most prevalent and aggressive primary brain tumors, characterized by profound tumor heterogeneity, poor prognosis, and limited therapeutic options. In recent years, metabolic reprogramming has emerged as a critical hallmark of glioma pathobiology. Dysregulated metabolic pathways not only supply energy and biosynthetic precursors but also remodel the tumor microenvironment (TME). These changes drive proliferation, invasion, and stemness, while promoting immune evasion and resistance to conventional therapies. Despite notable progress in molecular characterization and multi-omics technologies, the mechanistic links between metabolic plasticity, immune suppression, and therapeutic resistance remain incompletely resolved, and effective metabolism-targeted interventions are still lacking.

This Research Topic aims to consolidate mechanistic, translational, and early clinical evidence delineating how metabolic plasticity governs glioma biology, the TME, and treatment response. We seek studies that explore the crosstalk between tumor metabolism and immune regulation, and uncover novel mechanisms of treatment resistance. We particularly welcome integrative analyses leveraging spatial transcriptomics, single-cell multi-omics, metabolomics, and in vivo metabolic imaging to map metabolic heterogeneity and its therapeutic liabilities. This Research Topic will include both adult and pediatric gliomas, including diffuse midline glioma with H3K27 alteration, as defined by the WHO Classification of Tumors of the Central Nervous System, 5th Edition (2021). Brain metastases arising from systemic malignancies are excluded. Bioinformatic or in silico studies without experimental or clinical validation, such as functional assays in glioma models or verification using patient-derived samples from institutional cohorts, will be considered out of scope for this Research Topic. By curating convergent insights across model systems and patient cohorts, this collection aims to define actionable strategies that enable precision medicine for patients with glioma.

We welcome Original Research, Reviews, and Perspectives in the following areas (but not limited to):

1. Mechanistic studies of metabolic pathways in glioma biology.
2. Crosstalk between tumor metabolic reprogramming and the immune microenvironment.
3. Metabolism-driven resistance to radiotherapy, chemotherapy, and immunotherapy.
4. Novel metabolic biomarkers for diagnosis, prognosis, and therapeutic monitoring.
5. Application of spatial transcriptomics, single-cell sequencing, and metabolomics to dissect glioma metabolic heterogeneity.

Submissions that bridge basic mechanisms with translational and clinical implications will be prioritized, aiming to accelerate progress in the understanding and treatment of glioma.