Novel targets and approaches in advanced prostate cancer

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Abstract
The development of therapeutic resistance is the underlying cause for most cancer deaths. By understanding the molecular basis of resistance to androgen withdrawal and chemotherapy in prostate cancer, the rational design of targeted therapeutics is possible. We review new treatment options for men with advanced prostate cancer. Although the taxanes currently represent the most active chemotherapeutic agents and standard of care for first-line treatment of metastatic hormone-refractory prostate cancer, most patients eventually progress because of intrinsic or acquired drug resistance. In recent years, increased knowledge of cancer progression and therapeutic resistance has identified many gene targets that regulate apoptosis, proliferation, and cell signalling. To date, numerous novel compounds have entered clinical trials as either single agents or in combination with cytotoxic chemotherapy. Even though hormone-refractory prostate cancer is still incurable, it is not untreatable. As cancer cells are proficient at adapting to therapeutic stressors, a combination regimen with drugs that target crucial cellular networks like the apoptotic rheostat may be more promising than treatment with highly selective single-target agents. Recent findings are very hopeful, but challenges remain to demonstrate effective antitumour activity in phase III trials with survival as the principal endpoint.