Multidrug Resistance in Prostate Cancer

Advanced hormone-refractory prostate cancer remains a therapeutic challenge, because all available pharmaceutical concepts have been ineffective in improving cancer-specific survival. Failure of chemotherapy may be caused by multidrug resistance (MDR) mechanisms protecting cancer cells against cytotoxic drugs, and the question arises whether prostate cancer is also using MDR principles resulting in resistance against chemotherapeutic agents. In consequence, an array of diverse pathways known to lead to MDR such as MDR1, MRPs, glutathione, and apoptosis have been examined and partially established at varying degrees in hormone-refractory prostate cancer. Thus, evidence keeps accumulating for the involvement of some MDR mechanisms in the chemoresistance of prostate cancer in vitro and in vivo. For some of them, e.g. MRP1, functional expression appears to be probable. This lends credit to the idea that reversal, circumvention, or overcoming of MDR pathways in advanced prostate cancer may be feasible and will lead to new avenues with improved treatment efficacy in otherwise intractable disease.