RNAi analysis of the ATP-binding cassette (ABC) family o

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Extensive associative gene expression data has been developed showing links between the expression of key members of the ABC family of proteins and resistance to many of the most commonly used anti-cancer chemotherapeutic agents. Current methods to analyze the direct functional consequence of the expression of the multiple drug resistance (MDR) proteins has been hampered by the lack of specificity of drug inhibitors, and the probable overlapping functional effect of these proteins when tumor cells develop MDR. The Laboratory of Cell Biology, CCR has recently identified a compound that appears to specifically be cytotoxic to cells over expressing MDR-1 (ABC-B1). Using fully characterized siRNAs corresponding to ABC-B1 we have now shown that MDR-1 expression does modulate the sensitivity of cells to this compound. We are continuing to collaborate with LCB to further understand the mechanism of action of this and related drugs. This data was presented as part of an Oral presentation at the 2005 AACR meeting and is included within a manuscript recently submitted for publication.