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ACS Chem. Biol. 1 (5), 271–273
10.1021/cb600215q
Web Release Date: June 16,
2006
Copyright © 2006 American Chemical Society
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The Great Multidrug-Resistance Paradox
Vivien Y. Chen, and Gus R. Rosania*
Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, Michigan 48109
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*To whom correspondence should be addressed. E-mail: grosania#umich.edu.
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.
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