Determinants of 5-fluorouracil sensitivity in human tumors

It is not apparent that advanced human carcinomas of the breast or the large bowel are conprised of at least two populations: those responding to treatment with 5-fluorouracil (approximately 20 per cent) and those unresponsive to this drug. This classification cannot be made before chemotherapy on the basis of any clinical parameter. Biochemical parameters to distinguish between responding and nonresponding tumors are being sought in this laboratory. Techniques have been developed to measure thymidylate synthetase, the target enzyme for 5-fluorouracil, 5-fluoro-2'-deoxyuridylate, the active form of the antimetabolite, and 2'-deoxyuridylate, the naturally occuring competing metabolite. These methods are sufficiently sensitive to permit analysis of these parameters in needle biopsy specimens, and do not require exposure of patients to radioisotopes.