Pharmacy World and Science

, Volume 16, Issue 2, pp 104–112 | Cite as

New targets for pyrimidine antimetabolites for the treatment of solid tumours

2: Deoxycytidine kinase
  • Veronique W. T. Ruiz van Haperen
  • Godefridus J. Peters
Purine and Pyrimidine Metabolism

Abstract

Deoxycytidine kinase is an enzyme required for the activation of, for example, cytarabine, the most widely used agent for the chemotherapy of haematological malignancies. However, deoxycytidine kinase also plays an important role in the activation of several new agents used in the treatment of leukaemia, such as cladribine. Recently, a new cytidine analogue, gemcitabine, has shown impressive activity as a single agent against several solid malignancies (ovarian cancer, non-small cell lung cancer), demonstrating that in solid tumours deoxycytidine kinase can be an important target for the activation of antimetabolites. Studies on the regulation of deoxycytidine kinase have shown that the enzyme has a complicated regulation (feedback inhibition by the product and regulation by ribonucleotides). Modulation of deoxycytidine kinase activity has already been shown to be an effective way to improve the effect of cytarabine and will probably be a target for new therapies.

Keywords

Antimetabolites, antineoplastic Deoxyadenosine analogues Deoxycytidine kinase Deoxycytidine analogues Drug resistance 

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Copyright information

© Royal Dutch Association for the Advancement of Pharmacy 1994

Authors and Affiliations

  • Veronique W. T. Ruiz van Haperen
    • 1
  • Godefridus J. Peters
    • 1
  1. 1.Department of OncologyFree University HospitalMB Amsterdamthe Netherlands

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