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Camptothecin and topotecan are chemotherapeutic agents used as first line treatment of ovarian cancer, a lethal form of cancer with a 5 year survival rate of only 19%. The two drugs are natural products that exhibit antitumor activity by a common mechanism and are transported out of the cell by multidrug resistance-associated protein 1 (MRP1). MRP1 belongs to a superfamily of cytoplasmic membrane proteins that is also responsible for the transport of organic cations and small hydrophobic molecules. In addition, MRP1 has been found to actively pump glutathione (GSH) conjugates and several coenzymes out of the cell, a process known as “chaperoning”. Recent studies indicate that resistance to camptothecin and topotecan is mediated, in part, by the expression and activity of MRP1. Studies using MRP1-expressing resistant human ovarian cancer cell lines indicated that MRP1 confers resistance by both reducing the intracellular concentrations of camptothecin and topotecan and by facilitating the efflux of the drugs out of the cell. MRP1-mediated resistance to camptothecin and topotecan is not evident in cultured resistant cells lines that do not express MRP1. This suggests that the presence of MRP1 is necessary to maintain resistance. In addition, although both MRP1 and BCRP are capable of facilitating the efflux of camptothecin and topotecan out of the cell, MRP1 may appear to be

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