The Dual Role of ABC Transporters in Drug Metabolism and Resistance to Chemotherapy

For many drugs, the liver is the major site of metabolism. Uptake transporters from the solute carrier superfamily, cytochrome P450 enzymes, and efflux transporters from the adenosine triphosphate (ATP) binding cassette (ABC) transporters play major roles in systemic pharmacokinetics and drug-drug interactions. Solute carriers may facilitate drug passage from blood to the liver for further processing by metabolizing enzymes and efflux transporters. This chapter reviews the dual role of ABC transporters in drug metabolism and cancer multidrug resistance. It highlights the critical role of polymorphisms in treatment success. ABC transporter encoding genes are widely dispersed in the genome and show a high degree of sequence identity among eukaryotes. They translocate a wide range of substrates across cell or organelle membranes using the energy from ATP hydrolysis. The survival benefit of systemic chemotherapy in the treatment of liver cancer is only marginal at best.