Lactate in the tumor microenvironment: A rising star for targeted tumor therapy

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.

The combined signatures of telomere and immune cell landscape provide a prognostic and therapeutic biomarker in glioma

“…Extensive research is currently being conducted on exosome-based immunotherapy ( 59 , 60 ). It is noteworthy that metabolic molecules exert a substantial influence on the immune environment, thereby impacting disease progression ( 61 – 63 ). Moreover, the equilibrium of cytokines holds significant sway over the advancement of diseases ( 64 ).…”

Neurotransmitter receptor-related gene signature as potential prognostic and therapeutic biomarkers in colorectal cancer

“…The Weighted Gene Co-expression Network Analysis (WGCNA) method ( Langfelder and Horvath, 2008 ; Li et al, 2023 )was utilized to identify potential modules related to different subclusters of the DEGs expression matrix of TCGA. Abnormal samples were filtered out, and the Pearson correlation coefficient was calculated to construct the correlation adjacency matrix.…”

Cancer metabolism and carcinogenesis

“…While the Warburg effect continues, the lactate produced is not a useless waste product. Lactate is not only important for tumor invasion, metastasis, and angiogenesis [ 24 , 25 ], but also has immunosuppressive functions, such as inducing and recruiting immunosuppressive cells and molecules, thereby promoting tumor development and escape [ 26 , 27 ]. Cancer cell-derived lactate can induce the expression of vascular endothelial growth factor (VEGF) and arginase 1 (Arg1) through HIF-1α signaling pathway, which promotes the polarization of tumor-associated macrophages (TAMs) toward the M2 phenotype, enabling TAMs to promote tumor growth [ 28 ].…”