Multidrug Resistance

Abstract

The past decade has seen the successful application of genetic techniques in the dissection of the most important phenotypes of cancer cells. In the case of drug resistance mechanisms, the elucidation of the genes involved in resistance to anticancer agents has led to new and unexpected information about tumor physiology and may well open therapeutic options by virtue of reversing clinical chemoresistance. The experimental characterization of defined multidrug resistance factors, such as P-glycoprotein, multidrug resistance associated protein, topoisomerase, or glutathione-S-transferase in urologic malignancies, is now relatively comprehensive, allowing for an initial analysis. Clinical studies on some of these concepts have been started and will be the subject of careful scrutiny. We expect that they will have a considerable impact on the way certain urologic anticancer strategies will be pursued in the future.

Proteomics for studying cancer cells and the development of chemoresistance

“…Another form of drug resistance in tumour cells arises from the intracellular detoxification of anticancer agents by glutathione-S-transferases, a group of intracellular enzymes consisting of three different isoenzymes, m, p, s [39,[53][54][55][56]. Increased activities of one of the isoforms can be responsible for the development of chemoresistance towards ciaplatin, 1-3-bis(2-chloroethyl)-1-nitrosourea, doxorubicin and daunorubicin especially in ovarian and gastrointestinal tumours.…”