[Cytotoxic nucleoside analogues--metabolism, activity and resistance].
BACKGROUND
Cellular resistance is an increasing problem in the treatment of haematological malignancies and solid tumours with cytotoxic nucleoside analogues. Studies on cellular models and clinical samples have allowed insight into the mechanisms behind this resistance.


METHODS
An overview of cytotoxic nucleoside analogues, their metabolism and their mechanism of action is presented. Studies on resistance to nucleoside analogues are reviewed. Results were collected from the literature in the PubMed database and from research in our laboratory.


CONCLUSIONS
Variations in the activity of nucleoside transporters and proteins of the intracellular metabolism are implicated in the result of treatment with nucleoside analogues. These proteins are kinases, 5'-nucleotidases and deaminases. Mechanisms identified in cell models or in samples from non-responding patients should be validated in treated patients. These mechanisms are prognostic factors for the clinical outcome in nucleoside analogue-treated patients.
Jordheim
Lars Petter
LP
INSERM U590, Laboratoire de Cytologie Analytique, Faculté de Médecine Rockefeller, 8 Avenue Rockefeller, 69008 Lyon, France. jordheim@yahoo.com
D000964:Antimetabolites, Antineoplastic / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D033703:Nucleoside Transport Proteins / Q000378:metabolism; D009705:Nucleosides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D033703:Nucleoside Transport Proteins; D009705:Nucleosides