Nucleoside analogues and nucleobases in cancer treatment.
Cytotoxic nucleoside analogues and nucleobases were among the first chemotherapeutic agents to be introduced for the medical treatment of cancer. This family of compounds has grown to include a variety of purine and pyrimidine nucleoside derivatives with activity in both solid tumours and malignant disorders of the blood. These agents behave as antimetabolites, compete with physiological nucleosides, and interact with a large number of intracellular targets to induce cytotoxicity. Progress has recently been made in the identification and characterisation of nucleoside transporters and the enzymes of nucleoside metabolism. In addition, there is now greater understanding of the molecular mechanisms of anticancer nucleoside activity, which provides opportunities for potentiating their antitumour effects. Strategies to optimise intracellular analogue accumulation and to enhance cancer-cell selectivity are proving beneficial in clinical trials.
Unité INSERM 453, Laboratoire de Cytologie Analytique, Faculté de Médecine Rockefeller, Lyon, France. fgalma@rockefeller.uni-lyon1.fr
Carlos M
CM
Galmarini
John R
JR
Mackey
Charles
C
Dumontet
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D011684:Purine Nucleosides / Q000627:therapeutic use; D011685:Purine Nucleotides / Q000627:therapeutic use; D011741:Pyrimidine Nucleosides / Q000627:therapeutic use; D011742:Pyrimidine Nucleotides / Q000627:therapeutic use
D000970:Antineoplastic Agents; D011684:Purine Nucleosides; D011685:Purine Nucleotides; D011741:Pyrimidine Nucleosides; D011742:Pyrimidine Nucleotides