5-Fluorouracil (5-FU) resistance and the new strategy to enhance the sensitivity against cancer: Implication of DNA repair inhibition

5-Fluorouracil (5-FU) has been an important anti-cancer drug to date. With an increase in the knowledge of its mechanism of action, various treatment modalities have been developed over the past few decades to increase its anti-cancer activity. But drug resistance has greatly affected the clinical use of 5-FU. Overcoming this chemoresistance is a challenge due to the presence of cancer stem cells like cells, cancer recurrence, metastasis, and angiogenesis. In this review, we have systematically discussed the mechanism of 5-FU resistance and advent strategies to increase the sensitivity of 5-FU therapy including resistance reversal. Special emphasis has been given to the cancer stem cells (CSCs) mediated 5-FU chemoresistance and its reversal process by different approaches including the DNA repair inhibition process.