Cancer cells are constantly being selected for survival and proliferation. During this process, tumor cells often co-opt basic physiological mechanisms to protect themselves from toxic chemotherapy. Of these mechanisms, the one that is most commonly encountered in laboratory studies is the increased cellular efflux of a broad class of cytotoxic drugs that is mediated by a family of energy-dependent transporters, known as ATP-binding cassette (ABC) proteins. Although 48 human ABC transporters have been described, only a handful are likely to be involved in drug resistance. These include P-glycoprotein (Pgp), the multidrug resistance associated protein (MRP), and the breast cancer resistance protein (BCRP), also termed ABCG2. In this chapter, we will provide an overview of the general structural and mechanistic features of the human ABC transporters thought to be involved in multidrug resistance in cancer cells. These transporters can no longer be understood only as candidate drug targets for overcoming multidrug resistance. Rather, these transporters are involved in multiple normal tissues in protection from drugs and xenobiotics. These include the blood brain barrier, oral bioavailability of drugs and xenobiotics through expression of transporters in the GI tract, drug disposition, and fetal protection through expression at the maternal-fetal barrier. We describe emerging information related to their potential role in drug and xenobiotic resistance and argue that studies of this drug resistance mechanism should continue in the laboratory and in the clinic.
- ABC transporter
- Drug resistance
- Drug transporters
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Biochemistry, Genetics and Molecular Biology(all)