MM Chandiwal P.D. Hinduja National Hospital & Medical Research Centre, Mumbai
Source of Support: None, Conflict of Interest: None
Tomudex (ZD 1694) is a new antifolate which is a specific inhibitor of thymidylate synthase (TS). It has been found to be active in colonic malignancy, either as primary of secondary line therapy. We have used tomudex as a second line treatment in a case of advanced primary colonic carcinoma and partial response was observed. The cytotoxic activity of tomudex is dependent upon uptake into cells via the reduced folate carrier and subsequent metabolism to polyglutamate forms which are approximately sixty fold more active as TS inhibitors. Rational design of the folate TS inhibitor was based on extensive understanding of relationship between chemical structure and biological properties and of analog interactions with TS transport proteins and folypolyglutamase synthase. The development of these folate based TS inhibitor exemplifies a targeted approach to design of new cancer chemotherapeutic agents.