5-Fluorouracil (5-FU)-induced organ toxicities: mechanisms, management, and prevention strategies

Fluoropyrimidines are a class of chemotherapy drugs used to treat various solid tumors. 5-Fluorouracil (5-FU) an antimetabolite in the fluoropyrimidine family, which has shown remarkable efficacy against a variety of solid tumors, is a crucial medication in the treatment of cancer. However, severe organ toxicities frequently restrict its therapeutic potential. Our current knowledge of the intricate processes underlying 5-FU-induced toxicities, such as cellular absorption, metabolism, disruption of DNA synthesis, interference with RNA processing, and cell cycle regulation, is consolidated in this thorough study. 5-FU toxicity affects the cardiovascular, neurological, gastrointestinal, hepatic, renal, hematological, and pulmonary systems and includes a number of mechanisms, including oxidative stress, inflammation, and endothelial dysfunction. With documented severe toxicity occurrences varying from 0.55% to 40% depending on the affected organ, genetic differences, especially in drug-metabolizing enzymes like dihydropyrimidine dehydrogenase (DPD), are important in predicting toxicity risk. Individual susceptibility to these toxicities has been found to be significantly influenced by patterns of polymorphism peculiar to a population. While new research points to the possible advantages of certain protective agents, current management approaches mostly focus on supportive care and dose modifications. Pharmacogenomic testing has demonstrated potential in lowering the risk of serious toxicities, particularly for variations in the DPYD gene. Improved therapy techniques, such as genetic profile-based individualized dosing and improved monitoring protocols, have been made possible by a clearer knowledge of these pathways.