TYMS and digestive system neoplasm: For instance, 5-fluouracil (5-FU) and raltitrexed are thymidylate synthase (TS) inhibitors that inhibit thymidine synthesis and DNA replication and repair, yet amplification or point mutations of the TS gene within gastrointestinal tumor cells generate TS overexpression or conformational changes which lower inhibitor affinity and induce drug resistance (22, 23).