Increasing the Efficacy of 5-Fluorouracil with Interferons: Preclinical, Clinical, and Pharmacokinetic Studies

  • Joseph A. Sparano
  • Scott Wadler
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 339)


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.


Folinic Acid Advanced Colorectal Cancer Modulate Agent Human Colon Cancer Cell Line Antineoplastic Effect 
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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Joseph A. Sparano
    • 1
  • Scott Wadler
    • 1
  1. 1.Albert Einstein Cancer CenterMontefiore Medical CenterBronxUSA

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