The relationship between tumor metabolism and 5-fluorouracil resistance

Fluorouracil (5-FU) is one of the most efficient chemotherapy drugs for the treatment of different malignancies, yet many patients encounter chemotherapy failure owing to the emergence of drug resistance. Hence, comprehending the mechanisms of 5-FU chemotherapy resistance is fundamental to overcoming this challenge and improving patient survival. Research over the past 30 years has shown that the emergence of drug resistance is a multifactorial phenomenon that is still poorly understood. Changes in tumor metabolism in relation to chemoresistance have garnered attention recently. Increasing evidence suggests that reprogramming tumor cell metabolic pathways alters tumor sensitivity to drug therapy. This review primarily summarizes the main tumor metabolic alterations linked with 5-FU resistance and promising chemotherapy combinations, to overcome 5-FU resistance from the perspective of intervening tumor metabolism and to identify the potential for metabolic targets in tumor therapy.