Review of recent studies on resistance to cytotoxic deoxynucleoside analogues.
Cytotoxic deoxynucleoside analogues are widely used in the treatment of haematological malignancies and solid tumours. Their metabolism and mechanisms of action are relatively well known, but with ongoing technological development, a continuous flow of scientific data is constantly adding new knowledge to this field. Thus, what was already a well-developed area some years ago has continued its expansion and become a better understood part of medical sciences. In order to keep abreast of the latest advances on cellular and clinical resistance to deoxynucleoside analogues, we have reviewed the recent literature and provide here an update on the subject. We have particularly focused on changes in gene products involved in the metabolic pathway of these drugs, such as membrane transporters, kinases, deaminases and 5'-nucleotidases. We also gave an overview on the chemical and biological development of modified deoxynucleoside analogues such as conjugates and pronucleotides.
Jordheim
Lars Petter
LP
International Agency for Research on Cancer, 150, Cours Albert Thomas, 69372 Lyon cedex 08, France. jordheim@yahoo.com
Dumontet
Charles
C
D015720:5'-Nucleotidase / Q000502:physiology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003853:Deoxyribonucleosides / Q000737:chemistry / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008954:Models, Biological; D009700:Nucleoside Deaminases / Q000502:physiology; D033703:Nucleoside Transport Proteins / Q000235:genetics / Q000494:pharmacology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000502:physiology; D012264:Ribonucleotide Reductases / Q000502:physiology
D000970:Antineoplastic Agents; D003853:Deoxyribonucleosides; D033703:Nucleoside Transport Proteins; D012264:Ribonucleotide Reductases; D017853:Phosphotransferases (Alcohol Group Acceptor); C020018:deoxyribonucleoside kinases; D015720:5'-Nucleotidase; D009700:Nucleoside Deaminases