In colorectal cancer, NK cell‐derived HMGB1 sterically blocks pyruvate‐exporting PKM2 tetramers, forcing tumor cells to abandon OXPHOS and triggering metabolic apoptosis; resistant clones compensate by upregulating the glutamine‐ME1‐NADPH axis to replenish the TCA cycle, achieving metabolic escape [107]. Here, HMGB1 is linked to neoplasm.