Lactylation in glioblastoma: mechanisms and therapeutic perspectives
- 1Department of Neurosurgery, Affiliated Hospital of Nantong University , ,
Abstract
Glioblastoma (GBM) is one of the most aggressive primary malignant tumors in the central nervous system. It is characterized by significant metabolic reprogramming, obvious glycolysis dependence, and excessive lactate accumulation. Rather than being merely a metabolic by-product, lactate is increasingly recognized as a signaling metabolite that can reshape tumor biology. The discovery of lactylation as a post-translational modification has established a direct mechanistic link between lactate metabolism, epigenetic regulation, and protein function. Evidence from GBM and broader glioma models indicates that lactylation regulates various carcinogenic processes, including tumor cell proliferation, maintenance of stemness, DNA damage repair, immune evasion, and resistance to chemotherapy and radiotherapy. Through these processes, lactylation couples metabolic states to transcriptional and signaling networks, thereby promoting malignant progression and treatment failure. This review summarizes current understanding of the molecular mechanisms regulating lactylation and systematically explores its role in the progression of GBM, treatment resistance, and remodeling of the tumor immune microenvironment. We also assess emerging strategies targeting lactate and the main obstacles in its clinical translation. Overall, lactylation may serve as an important regulatory interface connecting metabolic reprogramming and the malignant phenotype of GBM; however, its value as a clinical biomarker or therapeutic target still requires further validation.
Related
- Lactylation in liver fibrosis: from molecular mechanisms to targeted therapeutic strategies
- Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets
- The Circadian Clock in Glioblastoma: Mechanisms and Therapeutic Potential.
- Targeting the NLRP3 inflammasome in rheumatoid arthritis fibroblast-like synoviocytes: pathogenic mechanisms, therapeutic strategies, and translational perspectives
- Dexmedetomidine as a potential neuroprotective agent against Alzheimer’s disease: molecular mechanisms and therapeutic perspectives
BibTeX
@article{huang2026lactylation,
title = {{Lactylation in glioblastoma: mechanisms and therapeutic perspectives}},
author = {Long Huang and Boyu Huang and Shizhen Kuang and Yaohua Yan},
journal = {Frontiers in cell and developmental biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1940871},
url = {https://europepmc.org/article/PMC/PMC13728161},
note = {CC BY},
}
RIS
TY - JOUR
TI - Lactylation in glioblastoma: mechanisms and therapeutic perspectives
AU - Long Huang
AU - Boyu Huang
AU - Shizhen Kuang
AU - Yaohua Yan
PY - 2026
DA - 2026/10/20
JO - Frontiers in cell and developmental biology
DO - 10.3389/fcell.2026.1940871
UR - https://europepmc.org/article/PMC/PMC13728161
AB - Glioblastoma (GBM) is one of the most aggressive primary malignant tumors in the central nervous system. It is characterized by significant metabolic reprogramming, obvious glycolysis dependence, and excessive lactate accumulation. Rather than being merely a metabolic by-product, lactate is increasingly recognized as a signaling metabolite that can reshape tumor biology. The discovery of lactylation as a post-translational modification has established a direct mechanistic link between lactate metabolism, epigenetic regulation, and protein function. Evidence from GBM and broader glioma models indicates that lactylation regulates various carcinogenic processes, including tumor cell proliferation, maintenance of stemness, DNA damage repair, immune evasion, and resistance to chemotherapy and radiotherapy. Through these processes, lactylation couples metabolic states to transcriptional and signaling networks, thereby promoting malignant progression and treatment failure. This review summarizes current understanding of the molecular mechanisms regulating lactylation and systematically explores its role in the progression of GBM, treatment resistance, and remodeling of the tumor immune microenvironment. We also assess emerging strategies targeting lactate and the main obstacles in its clinical translation. Overall, lactylation may serve as an important regulatory interface connecting metabolic reprogramming and the malignant phenotype of GBM; however, its value as a clinical biomarker or therapeutic target still requires further validation.
SN - 2296-634X
ER -