Objective:

To summarize insights into lipid metabolic plasticity in glioblastoma (GBM) and discuss its mechanistic links to tumor microenvironment remodeling, ferroptosis regulation, and therapeutic resistance.

Approach:

• Lipid Metabolic Plasticity: The review defines lipid metabolic plasticity as the ability of GBM cells to switch between distinct lipid handling programs in response to environmental stressors.
• Adaptive Modules: Focuses on three interconnected adaptive modules: de novo lipogenesis and exogenous lipid uptake, cholesterol-dependent membrane remodeling, and lipid droplet-mediated stress buffering.

Key Findings:

• Lipid metabolic reprogramming is a critical hallmark of GBM progression and therapeutic resistance.
• GBM cells exhibit enhanced de novo lipogenesis, fatty acid uptake, cholesterol remodeling, and lipid droplet accumulation.
• Lipid metabolism influences tumor plasticity, oxidative stress adaptation, immune suppression, and stemness maintenance.
• Lipid metabolic alterations occur not only in tumor cells but also in tumor-associated immune and stromal compartments.

Interpretation:

Recent advances in spatial transcriptomics and single-cell metabolomics have improved understanding of lipid metabolic heterogeneity in GBM.

Limitations:

• The review does not provide specific clinical trial data or outcomes related to targeting lipid metabolism in GBM.
• Focuses primarily on metabolic pathways without extensive discussion on potential therapeutic agents.

Conclusion:

Targeting lipid metabolic pathways may impair tumor growth and reshape the tumor immune microenvironment.