Department of Cancer Medicine, Institut Gustave Roussy, University of Paris-Sud, 94800 Villejuif Cedex, France.
Cancer J. 2013 Jan-Feb;19(1):66-70. doi: 10.1097/PPO.0b013e31827f123e.
Prostate cancer is the most common male cancer. About 90% of metastatic patients will develop bone metastases. Bone disease is responsible of pain, deterioration of quality of life and serious bone complications. Proliferation of prostate cancer cells in the bone marrow induces osteoclast activation and osteolysis. Targeting the bone microenvironment reduces morbidity. Relevant preclinical and clinical studies of bone-targeted therapies in castration-resistant prostate cancer were identified in PubMed and clinical trial databases. Different drugs are available or in development that target bone resorption (bisphosphonates, RANK ligand inhibitors), bone formation (endothelin 1 inhibitors), cancer cell migration (SRC-family kinase inhibitors, vascular endothelial growth factor-MET inhibitors), and survival (radiopharmaceuticals). In phase III trials, zoledronic acid, denosumab, and radium-223 were shown to significantly delay skeletal-related events. Radium-223 was also shown to improve overall survival. Biomarkers of bone resorption (urinary N-telopeptide) and bone making (alkaline phosphatase) have an independent prognostic impact. Targeting the bone microenvironment is an important component of castration-resistant prostate cancer management to reduce bone complications and improve overall survival. Biomarkers of bone turnover have an independent prognostic impact.
前列腺癌是最常见的男性癌症。约 90%的转移性患者将发展为骨转移。骨病会导致疼痛、生活质量下降和严重的骨并发症。前列腺癌细胞在骨髓中的增殖会诱导破骨细胞的激活和骨溶解。靶向骨微环境可以降低发病率。在 PubMed 和临床试验数据库中，确定了针对去势抵抗性前列腺癌的骨靶向治疗的相关临床前和临床研究。有不同的药物可用于靶向骨吸收（双膦酸盐、RANK 配体抑制剂）、骨形成（内皮素 1 抑制剂）、癌细胞迁移（Src 家族激酶抑制剂、血管内皮生长因子-MET 抑制剂）和存活（放射性药物）。在 III 期临床试验中，唑来膦酸、地舒单抗和镭-223 被证明可显著延迟骨骼相关事件。镭-223还被证明可以提高总生存率。骨吸收的生物标志物（尿 N 端肽）和骨形成的生物标志物（碱性磷酸酶）具有独立的预后影响。靶向骨微环境是去势抵抗性前列腺癌管理的重要组成部分，可减少骨并发症并提高总生存率。骨转换生物标志物具有独立的预后影响。
