Circumvention of multidrug resistance in genitourinary tumors.
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.[1]References
- Circumvention of multidrug resistance in genitourinary tumors. van Brussel, J.P., Mickisch, G.H. International journal of urology : official journal of the Japanese Urological Association. (1998) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
