AUTHOR=Li Zhangzuo , Wang Qi , Huang Xufeng , Yang Mengting , Zhou Shujing , Li Zhengrui , Fang Zhengzou , Tang Yidan , Chen Qian , Hou Hanjin , Li Li , Fei Fei , Wang Qiaowei , Wu Yuqing , Gong Aihua TITLE=Lactate in the tumor microenvironment: A rising star for targeted tumor therapy JOURNAL=Frontiers in Nutrition VOLUME=10 YEAR=2023 URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1113739 DOI=10.3389/fnut.2023.1113739 ISSN=2296-861X ABSTRACT=

Metabolic reprogramming is one of fourteen hallmarks of tumor cells, among which aerobic glycolysis, often known as the “Warburg effect,” is essential to the fast proliferation and aggressive metastasis of tumor cells. Lactate, on the other hand, as a ubiquitous molecule in the tumor microenvironment (TME), is generated primarily by tumor cells undergoing glycolysis. To prevent intracellular acidification, malignant cells often remove lactate along with H+, yet the acidification of TME is inevitable. Not only does the highly concentrated lactate within the TME serve as a substrate to supply energy to the malignant cells, but it also works as a signal to activate multiple pathways that enhance tumor metastasis and invasion, intratumoral angiogenesis, as well as immune escape. In this review, we aim to discuss the latest findings on lactate metabolism in tumor cells, particularly the capacity of extracellular lactate to influence cells in the tumor microenvironment. In addition, we examine current treatment techniques employing existing medications that target and interfere with lactate generation and transport in cancer therapy. New research shows that targeting lactate metabolism, lactate-regulated cells, and lactate action pathways are viable cancer therapy strategies.