Increasing the efficacy of 5-fluorouracil with interferons: preclinical, clinical, and pharmacokinetic studies.

Abstract

The interferons are a family of glycoproteins which possess potent antiviral, immunomodulatory, and antiproliferative effects in vivo 1. The interferons also additively or synergistically enhance the efficacy of many cytotoxic agents against a number of cultured human adenocarcinoma, squamous cell carcinoma, and lymphoid tumor cell lines in vivo 1. In particular, interferon-α synergistically augments the antineoplastic effect of 5-fluorouracil (5-FU) in cultured human colonic adenocarcinoma cell lines in vivo.2 At the cellular level, the interferons act in a variety of ways to augment the antineoplastic effect of 5-FU by: (1) increasing the activity of thymidine Phosphorylase 3, thereby augmenting the anabolism of 5-FU to its active metabolite, fluorodeoxyuridylate monophosphate, (2) enhancing inhibition of thymidylate synthase, the target enzyme of 5-FU, at the post-transcriptional level 4, (3) inhibiting thymidine salvage pathways 3, and (4) by enhancing 5-FU induced DNA damage 5.KeywordsFolinic AcidAdvanced Colorectal CancerModulate AgentHuman Colon Cancer Cell LineAntineoplastic EffectThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.