Drug resistance to cytotoxic nucleoside analogues.
Nucleoside analogues are widely used for the treament of hematological malignancies and solid tumors. Their activity is based on the interference with cellular targets involved in the metabolism of physiological nucleosides and DNA synthesis. Unfortunately, various resistance mechanisms decrease the activity of these drugs, reducing their clinical efficacy. Here, we review different resistance mechanisms responsible for decreased in vitro and in vivo nucleoside analogue activity, and some of the strategies proposed to circumvent constitutive or acquired drug resistance.
Jordheim
L
L
INSERM U590, Laboratoire de Cytologie Analytique, Faculté de Médecine Rockefeller, 8, Avenue Rockefeller, 69008 Lyon, France. jordheim@yahoo.com
Galmarini
C M
CM
Dumontet
C
C
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D033703:Nucleoside Transport Proteins / Q000378:metabolism; D009705:Nucleosides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D033703:Nucleoside Transport Proteins; D009705:Nucleosides