Drug resistance to cytotoxic nucleoside analogues

Curr Drug Targets. 2003 Aug;4(6):443-60. doi: 10.2174/1389450033490957.


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.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / metabolism
  • Antineoplastic Agents* / pharmacology
  • Cell Survival / drug effects
  • Drug Resistance, Neoplasm*
  • Humans
  • Nucleoside Transport Proteins / metabolism
  • Nucleosides* / chemistry
  • Nucleosides* / metabolism
  • Nucleosides* / pharmacology
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Nucleoside Transport Proteins
  • Nucleosides