The Role of Nucleoside Transport in the Antineoplastic Activity of Purine Nucleoside Chemotherapeutic Agents

Carol   E.   Cass; Karen   M.   King

Abstract

Purine nucleoside analogues are extensively used in the treatment of malignancies and viral diseases. For example, cladribine and fludarabine are two purine nucleoside analogues that have activity in the treatment of chronic lymphocytic leukemias. These chemotherapeutic agents exert their cytotoxic actions through interactions with intracellular targets. Due to their hydrophilic nature, many purine nucleoside analogues do not readily diffuse across cell membranes at therapeutic concentrations. The presence or absence of mediated transport systems will therefore have an impact on their pharmacological activities. There are two families of nucleoside transporters with members in human (h) cells and tissues: the equilibrative nucleoside transporters (hENTs) and the concentrative nucleoside transporters (hCNTs). These transporter proteins mediate the uptake of both physiologic nucleosides and nucleoside analogue chemotherapeutic agents. It has been documented that permeant specificity, tissue distribution and cellular localization of these transporters contribute to the antineoplastic activity of the purine nucleoside analogues. This article will review current knowledge of the role of nucleoside transport proteins in the cytotoxic actions of purine nucleoside analogues.

Keywords: Anti-cancer purine nucleoside analogues, nucleoside transporters

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