Abstract
Much of the attention devoted to the elucidation of multidrug-resistance mechanisms in tumor cells has focused on transmembrane drug transporters and their ability to pump drug molecules from the cytosol to the extracellular medium. However, intracellular drug concentrations often remain high in drug-resistant cells and therefore do not explain how drug pumping at the plasma membrane confers multidrug resistance. Recent work indicates how drug sequestration in cytoplasmic organelles can account for these paradoxical results and how cellular pharmacokinetics may be exploited to target the activity of small molecules to specific cell types.