Nucleoside anticancer drugs: the role of nucleoside transporters in resistance to cancer chemotherapy.
The clinical efficacy of anticancer nucleoside drugs depends on a complex interplay of transporters mediating entry of nucleoside drugs into cells, efflux mechanisms that remove drugs from intracellular compartments and cellular metabolism to active metabolites. Nucleoside transporters (NTs) are important determinants for salvage of preformed nucleosides and mediated uptake of antimetabolite nucleoside drugs into target cells. The focus of this review is the two families of human nucleoside transporters (hENTs, hCNTs) and their role in transport of cytotoxic chemotherapeutic nucleoside drugs. Resistance to anticancer nucleoside drugs is a major clinical problem in which NTs have been implicated. Single nucleotide polymorphisms (SNPs) in drug transporters may contribute to interindividual variation in response to nucleoside drugs. In this review, we give an overview of the functional and molecular characteristics of human NTs and their potential role in resistance to nucleoside drugs and discuss the potential use of genetic polymorphism analyses for NTs to address drug resistance.
Membrane Protein Research Group, University of Alberta, 11560 University Avenue, Edmonton, Alberta, Canada T6G 1Z2.
Vijaya L
VL
Damaraju
Sambasivarao
S
Damaraju
James D
JD
Young
Stephen A
SA
Baldwin
John
J
Mackey
Michael B
MB
Sawyer
Carol E
CE
Cass
D000970:Antineoplastic Agents / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D033703:Nucleoside Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D033703:Nucleoside Transport Proteins