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Expert Opin Drug Metab Toxicol. 2015 May;11(5):795-809. doi: 10.1517/17425255.2015.1028356. Epub 2015 Apr 2.

Influence of multidrug resistance and drug transport proteins on chemotherapy drug metabolism.

Author information

1
Dublin City University, National Institute for Cellular Biotechnology (NICB) , Glasnevin, Dublin 9 , Ireland +353 1 7005700 ; +353 1 7005484 ; Helena.Joyce@dcu.ie.

Abstract

INTRODUCTION:

Chemotherapy involving the use of anticancer drugs remains an important strategy in the overall management of patients with metastatic cancer. Acquisition of multidrug resistance remains a major impediment to successful chemotherapy. Drug transporters in cell membranes and intracellular drug metabolizing enzymes contribute to the resistance phenotype and determine the pharmacokinetics of anticancer drugs in the body.

AREAS COVERED:

ATP-binding cassette (ABC) transporters mediate the transport of endogenous metabolites and xenobiotics including cytotoxic drugs out of cells. Solute carrier (SLC) transporters mediate the influx of cytotoxic drugs into cells. This review focuses on the substrate interaction of these transporters, on their biology and what role they play together with drug metabolizing enzymes in eliminating therapeutic drugs from cells.

EXPERT OPINION:

The majority of anticancer drugs are substrates for the ABC transporter and SLC transporter families. Together, these proteins have the ability to control the influx and the efflux of structurally unrelated chemotherapeutic drugs, thereby modulating the intracellular drug concentration. These interactions have important clinical implications for chemotherapy because ultimately they determine therapeutic efficacy, disease progression/relapse and the success or failure of patient treatment.

KEYWORDS:

ATP-binding cassette transporters; cancer; chemotherapy drug metabolism; cytochrome P450; folate efflux; glucuronidation; glutathione S-transferase conjugates; multidrug resistance; solute carrier transporters

PMID:
25836015
DOI:
10.1517/17425255.2015.1028356
[Indexed for MEDLINE]

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