ABCB1 and cancer: While the specifics are not necessarily generalizable, determinants of response to nucleotide drugs illustrate key components of therapeutic efficacy: (i) drugs enter the tumor cells via specific SLC transporters; (ii) SLC transporter expression levels and function are major determinants of drug activity; and (iii) cancers may acquire resistance to drugs by reducing intratumoral drug concentrations via modulation of metabolic enzymes, downregulation of uptake transporters, or upregulation of ABC efflux transporters such as Multi-Drug Resistance Gene (MDR1/ABCB1).