Abstract
Gastrointestinal tumours are one of the most common types of cancer. Therapeutic options include surgery, radiotherapy, local ablation techniques, targeted agents, and chemotherapy. Fluoroprimidines are one of the most active drug families in digestive tumours and remains the cornerstone of the most commonly used chemotherapy schemes. We review the molecular basis of thymidylate synthase inhibition and the mechanisms of action of 5-fluorouracil, next generation oral fluoropyrimidines (capecitabine, tegafur and the latest S-1 and TAS-102) and antifolates. In addition, mechanisms and biomarkers of resistance and toxicity are explored. Finally, new fluoropyrimidines development and clinical trials ongoing in digestive tumours are reviewed. Further research is necessary to avoid resistance mechanisms, improve clinical outcomes and continue reducing toxicities. Until new drugs become available, the optimization of current therapies should be a priority.
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