Glycation stress in glioma: a metabolic vulnerability and therapeutic target

Gliomas are primary brain tumors characterized by genetic heterogeneity, metabolic reprogramming, and resistance to therapy, which collectively contribute to tumor progression and aggressive clinical behavior. Heightened aerobic glycolysis in these tumors is associated with altered glycolytic flux and dysregulated metabolic landscape. The ubiquitous dicarbonyl metabolite methylglyoxal (MGO) is a highly reactive glycating agent produced from glycolytic intermediates. MGO is a major precursor of advanced glycation end products (AGEs), and excessive AGE accumulation is associated with disruption of cellular homeostasis. Inhibitors of key bioenergetic pathways have shown potential in glioma, indicating that altered glycolysis may create metabolic vulnerabilities that influence tumor cell survival. In this context, increased glycolytic flux in glioma may provide a mechanistic link between glycation stress and tumor progression. This review discusses the influence of glycation stress in glioma biology and emphasize the importance of considering genetic heterogeneity, redox landscape, and metabolic comorbidities to better understand glycation burden and inform therapeutic strategies.