The great multidrug-resistance paradox.
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.
Chen
Vivien Y
VY
Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, Michigan 48109, USA.
Rosania
Gus R
GR
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D015388:Organelles / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins