6533b827fe1ef96bd1286e4b

RESEARCH PRODUCT

Systemic treatment of bone metastases in castration-resistant prostate cancer (CRPC): pre-clinical to clinical point of view

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Abstract Prostate cancer (PCa) is the most common cancer and the third most common cause of cancer related mortality in men in the United States. Hormonal therapy remains the most effective therapy for patients with advanced prostate cancer, inhibiting proliferation and inducing apoptosis in tumor cells. Unfortunately, after short-term remissions (18–24 months), surviving tumor cells recur with castrate resistant prostate cancer (CRPC) with inevitable progression, development of metastases mainly in bone, and death within 2–3 years in most men. Improved understanding of the molecular basis underlying bone-specific metastases and resistance to ADT or chemotherapy will facilitate the rational design of targeted therapeutics. In addition to castrate resistant disease, a second unique characteristic of PCa progression is bone-predominant metastatic progression. The bone is the most prominent site for metastases in prostate cancer. Bone metastases are associated with a significant increase of pain and serious complications. Bone provides a rich microenvironment for establishment of PCa metastases, at least in part, because of its dense reservoir of growth regulatory factors, extracellular matrix proteins, and hydroxyapatite scaffolds to support tumor growth. Over the last few years, numerous gene targets that regulate tumor-bone stromal interaction have been identified, and many novel compounds have entered clinical trials either as single agents or in combination with cytotoxic chemotherapy. Due to rapid progress of this field, it is beyond the scope of this chapter to focus on molecular and cellular mechanisms involved in prostate cancer progression and bone metastases and will discuss incidence, morbidity and possible treatment strategies in this setting.