Solute Carriers

Abstract

Membrane transporters are important for regulating cellular and physiologic solute and fluid balance and can generally be grouped into two major classes—uptake and efflux. These proteins are critical to human physiology in the maintenance of normal homeostasis via transport of endogenous substrates, but are also important to the disposition of xenobiotics such as environmental toxins, dietary constituents, drugs, and their metabolites, thereby modulating or altering drug response. In particular, over the past decade, members of the solute carrier (SLC) superfamily, including the organic anion-transporting polypeptide (SLCO; OATP) family, the organic cation/anion/zwitterion transporter (SLC22; OCT and OAT) family, the concentrative nucleoside transporter (SLC28; CNT) family, and the equilibrative nucleoside transporter (SLC29; ENT) family, have been shown to have important physiologic, pathologic, and therapeutic implications. Although generally recognized as drug transporters, these proteins have only recently been determined to be important factors in the disposition of commonly used antineoplastic chemotherapeutic agents and thereby serve as key determinants of pharmacokinetics, pharmacodynamics, and pharmacogenetics. In this chapter, we focus on the field of solute carriers and provide a comprehensive overview of the significant and emerging roles these proteins play in anticancer drug disposition and response.