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Thymidylate synthase (TS) is an intracellular enzyme critical for de novo synthesis of DNA. In cancer, expression of TS is often elevated and becomes further elevated as a result of treatment with the most commonly used chemotherapeutic, 5-fluorouracil (5-FU). Resistance or lack of response to 5-FU is attributed to the elevation of TS activity. Overexpression of TS has been demonstrated in many types of tumors including breast, colon, gastric and melanoma and is usually predictive of shortened survival time.