The multifaceted functions of lactate and its translational potentials in cancer

As considered as a mere waste product historically, the biological functions of lactate have been overlooked for a long time. Over the past decades, accumulated data has implicated the multiple and substantial roles of lactate in physiological and pathological contexts, particularly in cancer. This review aims to provide a comprehensive overview about lactate biology in both health homeostasis and oncology. We first presented a systematic elaboration about lactate metabolism, including its property, production, transport, shuttling as well as sensing. Additionally, the multifaceted functions of lactate in tumor microenvironment were summarized to explore the underlying mechanisms during metabolic reprogramming, signaling molecule, immune modulation and epigenetic regulation. Furthermore, we assessed the current lactate-targeted strategies for cancer intervention, exploring the feasibility as therapeutic targets in clinical application. Finally, the unsolved challenges were outlined to propose illuminating directions for future investigations and accelerate its translation into clinical practice in this field.