Current Perspectives on the Role of Nrf2 in 5-Fluorouracil Resistance in Colorectal Cancer

Background: The antimetabolite, 5-Fluorouracil (5-FU), is the only chemotherapeutic drug to significantly improve 12-month survival rates of patients with Colorectal Cancer (CRC). However, resistance to 5-FU is a major obstacle to effective treatment. The mechanism of 5-FU resistance has been discovered but is not fully known. Nuclear factor-erythroid 2-related factor 2 (Nrf2), a master regulator of cellular defense against oxidative and electrophilic stresses, is considered a major factor in 5-FU resistance. Objective: The current study was conducted to discuss the role and mechanisms of Nrf2 in 5-FU resistance and to search for medicines or compounds that can reverse Nrf2-mediated 5-FU resistance. Methods: Literature was obtained by defining specific search terms and searching several databases. Results: Previous study suggested that overactivation of Nrf2 contributed to 5-FU resistance by regulating many cytoprotective genes. Interestingly, several medicines and compounds can repress 5-FU resistance mediated of Nrf2. Conclusion: This review describes the major 5-FU-resistance mechanisms of Nrf2 and summarizes the medicines/ compounds that can overcome them.