Antitumour activity of S-1 in combination with cetuximab on human gastric cancer cell lines in vivo.

This study aimed to assess the antitumour effect of a combination of cetuximab (Erbitux, a chimeric anti-epidermal growth factor receptor (EGFR) monoclonal antibody) and S-1, an oral 5-fluorouracil prodrug, on gastric cancer cell lines in vivo. Gastric cancer cell lines (SC-2 and SC-4) were transplanted subcutaneously into nude mice. In both cell lines, which have high EGFR expression and harbour K-ras wild-type alleles, treatment with a combination of cetuximab and oral S-1 resulted in significantly higher antitumour activity than treatment with cetuximab or S-1 alone. To investigate this potentiation of antitumour activity, the expression levels of thymidylate synthase (TYMS) were measured following administration of cetuximab. Cetuximab induced a decrease in expression of TYMS mRNA and protein. These findings suggest that cetuximab-mediated down-regulation of TYMS enhances the antitumour effect of S-1 and provide a rationale for designing novel combination chemotherapy regimens for patients with advanced gastric cancer.