Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
Int J Oncol. 2012 May;40(5):1313-20. doi: 10.3892/ijo.2012.1364. Epub 2012 Feb 9.
Prostate cancer is the most common cancer in men in Europe and the United States, and the third leading cause of death from cancer in Europe. Survival of prostate cancer cells is dependent on the activation of androgen receptors (AR), that are overexpressed in this tumor. Furthermore, ~90% of prostate cancer patients that respond to first-line androgen deprivation therapy (ADT) undergo rapid progression. This condition is defined as castration-resistant prostate cancer (CRPC). Docetaxel-based regimens significantly improve overall survival (OS) in patients with CRPC and represent the only treatment strategy approved by the Food and Drug Administration (FDA). Recently, abiraterone (second hormonal therapy) and cabazitaxel (new taxane) have been shown to improve survival in patients with CRPC who progressed following docetaxel-based chemotherapy. Vaccine therapy has also been demonstrated to improve OS in patients with asymptomatic or minimally symptomatic metastatic CRPC. Additional therapeutic targets have been analyzed in prostate cancer, including apoptosis, angiogenic receptors, vitamin D and Src pathways. Several phase II studies are ongoing. The high frequency of prostate cancer-related metastatic bone disease has led to consider this pathway as a therapeutic target. To this end, several bone-targeted agents have been investigated, most notably zoledronic acid, which is highly effective at stabilizing the bone and preventing skeletal complications. More recently, a nuclear factor-β ligand (RANKL) inhibitor, denosumab, has been developed for the treatment of bone metastases.
前列腺癌是欧洲和美国男性中最常见的癌症，也是欧洲癌症死亡的第三大原因。前列腺癌细胞的存活依赖于雄激素受体（AR）的激活，而这种受体在这种肿瘤中过度表达。此外，约 90%对一线雄激素剥夺治疗（ADT）有反应的前列腺癌患者会迅速进展。这种情况被定义为去势抵抗性前列腺癌（CRPC）。基于多西他赛的治疗方案显著改善了 CRPC 患者的总生存期（OS），并且是食品和药物管理局（FDA）批准的唯一治疗策略。最近，阿比特龙（二线激素治疗）和卡巴他赛（新型紫杉烷）已被证明可改善接受多西他赛化疗后进展的 CRPC 患者的生存。疫苗治疗也已被证明可改善无症状或有轻微症状的转移性 CRPC 患者的 OS。在前列腺癌中还分析了其他治疗靶点，包括细胞凋亡、血管生成受体、维生素 D 和Src 途径。目前正在进行几项 II 期研究。前列腺癌相关转移性骨病的高频率导致人们考虑将该途径作为治疗靶点。为此，已经研究了几种针对骨骼的药物，其中最著名的是唑来膦酸，它在稳定骨骼和预防骨骼并发症方面非常有效。最近，一种核因子-β配体（RANKL）抑制剂，地舒单抗，已被开发用于治疗骨转移。
