Role of Nucleoside Transporters in Nucleoside-Derived Drug Sensitivity

Abstract

Nucleoside-derived drugs are currently used clinically as anticancer drugs. To exert their pharmacological action first they need to enter into the cell across plasma membrane transporters and be metabolized. Thus, efficacy of treatment and acquisition of resistance can rely on a variety of events. In this article, we will focus in the role of nucleoside transporters in the sensitivity to nucleoside-derived drugs used in chemotherapy. Evidence of different transporter protein expression patterns in tumors compared to normal tissues, besides inter-individual variability in the levels of nucleoside transporters in tumors, suggest a major role of nucleoside transporters in the cytotoxicity of nucleoside analogs. In fact, different studies have linked nucleoside transporter function to drug sensitivity and clinical outcome in cancer patients. However, prospective clinical studies analysing nucleoside transporters and metabolic enzymes, as biomarkers of drug metabolism and action are required to better establish the role these proteins might play in cancer chemotherapy.

Keywords:

• Nucleoside transporters
• SLC28
• SLC29
• nucleoside analogs
• chemotherapy
• tumor

Acknowledgments

Work at the authors’ laboratory has been funded by grants SAF2008-00577 from MICINN (Spain), 36621/06 from FIPSE, and Direcció General de Recerca, DURSI, Generalitat de Catalunya. CIBER is an initiative of Instituto de Salud Carlos III, MICINN (Spain).

Present address: for M. M.-A.: Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, UK