Although 5-fluorouracil (5-FU) is still a vital chemotherapeutic treatment for several types of cancers, especially in gastrointestinal cancers like colorectal cancer (CRC), pancreatic cancer and gastric cancer, its long-term therapeutic effectiveness is severely limited by both innate and acquired resistance. Overexpression of thymidylate synthase (TYMS), elevation of dihydropyrimidine dehydrogenase (DPD), epithelial–mesenchymal transition (EMT), increased drug efflux through ABC transporters, and dysregulation of apoptotic signalling pathways are important mechanisms of resistance. With increasing data demonstrating their significance in modifying important molecular targets to overcome or mitigate resistance, recent studies have highlighted the potential of vitamins, herbal remedies, and nutritional supplements as adjuncts to conventional 5-FU therapy. Vitamin D, C, curcumin, allicin, EGCG, and omega-3 fatty acids have been shown to suppress TYMS expression, inhibit NF-κB signaling, reduce oxidative stress-mediated survival signaling, modulate apoptosis regulators (Bcl-2, Bax), and reduce drug efflux mechanisms in preclinical cancer models. Incorporating such supplementary strategies may improve patient quality of life, decrease treatment-related toxicities, and increase the effectiveness of 5-FU. This review presents integrated approaches for improving therapeutic outcomes in cancer care by synthesising current knowledge of 5-FU resistance mechanisms and critically analyzing the supportive roles of dietary supplements, vitamins, and phytochemicals in minimising the adverse effects related to 5-FU resistance.
Chandru et al. (Fri,) studied this question.