The Role of Fluoropirimidines in Gastrointestinal Tumours: from the Bench to the Bed

Abstract

Purpose

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.

Methods

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.

Results

In addition, mechanisms and biomarkers of resistance and toxicity are explored. Finally, new fluoropyrimidines development and clinical trials ongoing in digestive tumours are reviewed.

Conclusions

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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