Recent advances in 5-fluorouracil: Co-crystal synthesis, prodrug derivatives and modulation strategies to enhance anti-cancer activity

5-Fluorouracil (5-FU), a fluoropyrimidine analog of uracil, is an extensively employed chemotherapy drug to treat many cancers, including solid malignancies, melanoma, colorectal cancer, pancreatic cancer, and gastric cancer. Its mechanism of action involves disrupting mRNA translation and DNA synthesis. However, the effectiveness of 5-FU is limited by several factors, including its rapid breakdown into inactive forms, loss of site selectivity, and fast elimination from the body when used as a standalone therapy. To address these challenges and improve its therapeutic potential, researchers have explored various strategies over time. This review paper presents a comprehensive overview of various strategies aimed at enhancing the therapeutic efficacy of 5-FU. It covers the development of co-crystals, prodrugs, modulation approaches with co-administration, and derivatization techniques. Additionally, the review provides valuable insights into different carrier systems utilized for the targeted delivery of 5-FU, offering potential advancements in cancer treatment. By evaluating the rationale, advantages, and challenges associated with each approach, this paper highlights the ongoing efforts to optimize the use of 5-FU in cancer treatment.