OTDOncology Treatment Discovery3083-49962981-8079Bio-Byword Scientific Publishing Pty. Ltd.10.26689/OTD.v4i3.15719Articlehttps://artdesignp.com/journal/OTD/4/3/10.26689/OTD.v4i3.15719YangZijie,ChenChao,ZhangYinhua2026432026-10-20Colorectal cancer (CRC) ranks among the most prevalent and lethal malignancies worldwide. Metabolic reprogramming is a hallmark of CRC, in which the Warburg effect drives massive lactate accumulation in the tumor microenvironment (TME) at concentrations far exceeding those in normal tissues. Traditionally recognized as a glycolytic waste product, lactate is now defined as a pleiotropic signaling molecule that profoundly remodels TME homeostasis and tumor progression. This review focuses on how lactate modulates CRC immunosuppressive networks via metabolic reprogramming, signal transduction and epigenetic regulation, and summarizes current advances in lactate-targeted therapeutic strategies for CRC.Colorectal cancer, Lactate, Tumor microenvironment, Metabolic reprogramming, Immunosuppression, Histone lactylation, Monocarboxylate transporter, Targeted therapy