Therapeutic potential of RNA interference in drug-resistant cancers

Resistance including multidrug resistance to chemotherapy is a common clinical problem in patients suffering from cancer. Multidrug resistance is often mediated by overexpression of transmembrane xenobiotic transport molecules belonging to the superfamily of ATP-binding cassette (ABC)-transporters. Inhibition of ABC-transporters by low-molecular weight compounds in cancer patients has been extensively investigated in clinical trials, but the results have been disappointing. Thus, alternative experimental therapeutic strategies for overcoming multidrug resistance are under investigation. These include the application of RNA interference (RNAi) technology. Various RNA! strategies were applied to reverse multidrug resistance in different tumor models in vitro and in vivo, Results and conclusions of these RNAi studies as well as their potential impact for the development of potential RNA! therapeutics will be discussed.