The relevance of intracellular, extracellular, and inter-tissue lactate as metabolic fuel and signaling molecules that link the epigenetic-metabolic axis in cancer is considered challenging . The reason behind the gaps in understanding the role of lactate and its derived metabolic products such as lactyl-CoA is the lack of detection of lactate and lactyl-CoA at the physiological concentration at intracellular, extracellular, and inter-tissue levels. The lack of clear evidence on the levels of lactate and lactyl-CoA could be linked with constraints such as specific and efficient metabolite profiling methodologies and the highly shuttling and diffusive nature of lactate and lactyl-CoA in the tumor microenvironment.