For example, metformin (a classical agent for the treatment of diabetes mellitus) could be used to control the fluctuation of glucose and it was also found to be effective in reversing insulin-induced oxaliplatin resistance in human colon cancer HCT-116 cells [42]; and clinically, metformin was demonstrated to be helpful in improving OS in stage II-III CRC in adjuvant settings [43, 44]. Here, INS is linked to diabetes mellitus.