Glycolytic reprogramming in cancer: tumour cell metabolism, immune modulation, and therapeutic opportunities

Aberrant metabolism is a hallmark of tumours. Cancer cells develop metabolic patterns distinct from those of normal cells, characterized by the conversion of glucose into lactate under both aerobic and hypoxic conditions. The intermediates and end products generated in this process modulate the function and survival of immune cells within the tumour microenvironment (TME). In this review, we summarize recent advances in the interplay between glycolysis and the immune microenvironment, potential therapeutic targets within the glycolytic pathway, and the clinical translation of glycolysis-related molecules. Through in-depth research into the glycolytic process, it has been found that the aberrant glycolytic metabolism of tumor cells not only supports their own proliferation but also reshapes the tumor microenvironment. This, in turn, forces immune cells to alter their metabolic profiles, ultimately resulting in an imbalanced anti-tumor immune response. To date, multiple small-molecule inhibitors targeting key molecules and nodes in the glycolytic pathway have been developed, some of which demonstrate promising anti-tumor efficacy in preclinical models. The review emphasizes the significance of glycolysis in shaping the immune response within the TME and underscores the therapeutic potential of targeting glycolytic pathways, with several inhibitors showing promise for future clinical translation.