Drug Transporter Pharmacogenetics in Nucleoside-Based Therapies

Abstract

This article focuses on the different types of transporter proteins that have been implicated in the influx and efflux of nucleoside-derived drugs currently used in the treatment of cancer, viral infections (i.e., AIDS) and other conditions, including autoimmune and inflammatory diseases. Genetic variations in nucleoside-derived drug transporter proteins encoded by the gene families SLC15, SLC22, SLC28, SLC29, ABCB, ABCC and ABCG will be specifically considered. Variants known to affect biological function are summarized, with a particular emphasis on those for which clinical correlations have already been established. Given that relatively little is known regarding the genetic variability of the players involved in determining nucleoside-derived drug bioavailability, it is anticipated that major challenges will be faced in this area of research.

KEYWORDS::

• ABC
• chemotherapy
• nucleobase
• nucleoside
• pharmacogenetics
• plasma membrane transporter
• polymorphic variant
• SLC

Financial & competing interests disclosure

This research was supported in part by grants SAF2008-00577, CIBER (an initiative of Instituto de Salud Carlos III), FIPSE 36621/06 and 2009SGR624 (Generalitat de Catalunya) to MP-A. Ekaitz Errasti-Murugarren was initially funded by Ministerio de Ciencia e Innovación (MICINN) and is now a CIBER researcher. The Regulation of Transport Systems (RST) group belongs to the Spanish Network of Membrane Transporter Research (REIT) (MICINN). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This research was supported in part by grants SAF2008-00577, CIBER (an initiative of Instituto de Salud Carlos III), FIPSE 36621/06 and 2009SGR624 (Generalitat de Catalunya) to MP-A. Ekaitz Errasti-Murugarren was initially funded by Ministerio de Ciencia e Innovación (MICINN) and is now a CIBER researcher. The Regulation of Transport Systems (RST) group belongs to the Spanish Network of Membrane Transporter Research (REIT) (MICINN). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.