Chemotherapy is the principal strategy to systemically challenge metastasized
cancers of genitourinary origin. Unfortunately, the efficacy of
chemotherapy is often hampered by multidrug resistance, the resistance to a variety of structurally and functionally distinct
cytotoxic agents. Multidrug resistance can be either intrinsic or acquired, and can be caused by several mechanisms. The so-called classical multidrug resistance, mediated by the MDR1 gene product
P-glycoprotein, has been held mainly responsible for inferring the multidrug resistance phenotype on urologic
malignancies. However, several other multidrug resistance pathways have been identified. Multidrug resistance can be caused by the membrane-bound
multidrug-resistance-associated protein, the detoxifying
glutathione metabolism, the antiapoptotic
protein BCL2, and changes in levels or activity of the topoisomerase
enzymes. Strategies to overcome multidrug resistance of genitourinary
tumors have arisen from the better understanding of the
biologic and molecular mechanisms of multidrug resistance, and have been studied in experimental and clinical settings. However, attempts to modulate multidrug resistance in clinical renal cell, bladder, prostate, and
testicular cancer have not been very rewarding so far, despite the optimism that had arisen from experimental data. Nevertheless, application of novel
therapies to reverse multidrug resistance and to increase efficacy of
chemotherapy for
urologic cancers should be further pursued, within the setting of controlled clinical trials, to improve on current strategies.