Xiao Shuying, Zhang Suhang, Sun Kai, Huang Qibo, Li Qilin, Hu Chuanyu
Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Biomark Res. 2025 Oct 24;13(1):134. doi: 10.1186/s40364-025-00849-0.
Investigating cancer metabolism is of paramount importance for understanding tumor biology and developing novel therapeutic strategies. Lactylation, a posttranslational modification facilitated by the glycolytic product lactate, plays a crucial role in regulating oncogenic signalling pathways. This review provides a comprehensive analysis of lactate metabolism, including its biosynthesis, compartmentalized transport, enzymatic network and structural features of lactate dehydrogenases, transporters, lactyltransferases and deacetylases. These enzymes contribute to malignant tumor progression through metabolic reprogramming and modulation of the immune microenvironment. Importantly, we emphasize that integrating cancer subtype-specific lactylation profiles with core signatures reveals promising therapeutic opportunities for targeting lactate shuttles, histone, and nonhistone lactylation mechanisms, and transcriptional networks regulated by lactylation. In the present review, we highlight the significant potential of targeting glycolysis and lactylation modifications in tumors to improve the efficacy of cancer treatments.
