[Predicting drug efficacy-fluorinated pyrimidines (fluorouracil, S-1 and capecitabine)]

The elucidation in recent years of intracellular signaling mechanisms related to cancer cell growth has been accompanied by increases in both drug development and biomarker research. While treatment strategies using biomarkers have been established and put to clinical use for various types of cancers and medications, most are limited to drugs targeting specific molecules, and none have been established for traditional cytotoxic drugs. For fluoropyrimidines, the standard drugs used in chemotherapy for gastrointestinal cancer, biomarker research has been conducted on targets such as thymidylate synthase(TS), dihydropyrimidine dehydrogenase(DPD), and thymidine phosphorylase(TP). The results of research on these targets have recently been reported, albeit retrospectively, in a number of additional studies and large-scale clinical trials. While some studies suggested that there is future potential for these targets, in general, it appears that there are insufficient data for their clinical application as biomarkers at present. Given the advances made toward the realization of personalized medicine, the discovery of biomarkers for fluoropyrimidines is of great importance and warrants further study.