Multidrug Resistance in Prostate Cancer

Advanced hormone refractory prostate cancer constitutes a therapeutic challenge, because all available treatment strategies have failed to substantially increase cancer specific survival. Among these strategies, a multitude of chemotherapeutic approaches did not offer a superior life expectancy longer than a few months. Failure of chemotherapy may be caused by multidrug resistance (MDR) mechanisms protecting cancer cells against cytotoxic drugs. The question arises whether the MDR phenomenon plays a role in prostate cancer. Several pathways known to lead to MDR such as the P-glycoprotein (Pgp; MDR1), isoforms of the multidrug resistance associated protein (MRP), glutathione, apoptosis and topoisomerases have been examined and are reviewed in chapter 2. Evidence for the involvement of several MDR mechanisms in the chemoresistance of prostate cancer in vitro and in vivo is accumulating. Reversal, circumvention or overcoming of MDR pathways in advanced prostate cancer may be feasible and will lead to new strategies with improved treatment efficacy in otherwise untreatable disease.