ORIGINAL ARTICLE Thymidylate Synthase Gene Expression in Primary Tumors Predicts Activity of S-1–Based Chemotherapy for Advanced Gastric Cancer

Tumors expressing high levels ofthymidylate synthase (TS), the rate-limiting enzyme of de novo DNA synthesis, have poor sensitivity to fluoropyrimidine-based chemotherapy,1–4 and tumor levels of dihydropyrimidine dehydrogenase (DPD), a rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism, have been reported to inversely correlate with sensitivity to 5-FU– based chemotherapy.5–9 These observations have led to attempts to predict efficacy of 5-FU treatment by assessing TS and DPD levels in gastrointestinal tumors.5, 8–11 S-1 is a new oral fluoropyrimidine with high activity in gastric and colorectal cancer.12–14 The drug contains the poten