Recent Progress in the Therapeutic Modulation of Lactate for Cancer Treatment

Abstract Lactate is the end‐product of glycolysis activity, which is universally upregulated in most solid tumor indications. Increasing evidence shows that lactate is also involved in various tumor‐related events, presenting indispensable roles for supporting tumor growth, progression, and invasion. Typically, lactate in the tumor microenvironment (TME) can not only be exploited as an energy source for sustaining cancer cell survival but also function as a messenger modulator for signal transduction via receptor or non‐receptor pathways for cell communications therein. In addition, the presence of lactate substantially suppresses anti‐tumor immunity and mediates the epigenetic upregulation of key oncogenes via lysine lactylation of histone. In this review, a concise yet comprehensive summary on recent studies regarding the myriad roles and functions of lactate on tumor cells and TME is provided, based on which there is further discussion of the emerging antitumor strategies targeting the lactate metabolism including its biosynthesis and transporting. This review may facilitate the development of more effective antitumor therapies.