Novel strategies in the treatment of castration-resistant prostate cancer (Review)
Novel strategies in the treatment of castration-resistant prostate cancer (Review)
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DOI：
10.3892/ijo.2012.1364
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发表时间：
2012-05-01
影响因子：
5.2
通讯作者：
Dammacco, Franco
中科院分区：
文献类型：
--
作者：
Marech, Ilaria;Vacca, Angelo;Dammacco, Franco
前列腺癌是欧洲和美国男性最常见的癌症，也是欧洲第三大癌症死亡原因。前列腺癌细胞的存活依赖于雄激素受体(AR)的激活，雄激素受体在前列腺癌中过度表达。此外，与90%对一线雄激素剥夺疗法(ADT)有反应的前列腺癌患者一样，病情进展迅速。这种情况被定义为耐去势前列腺癌(CRPC)。基于多西紫杉醇的方案显著提高了CRPC患者的总存活率(OS)，是美国食品和药物管理局(FDA)批准的唯一治疗策略。最近，阿比特龙(第二种激素疗法)和卡巴西紫杉醇(新紫杉醇)被证明可以提高多西紫杉醇化疗后进展的CRPC患者的存活率。疫苗治疗也被证明能改善无症状或无症状的转移性CRPC患者的OS。前列腺癌的其他治疗靶点已经被分析，包括细胞凋亡、血管生成受体、维生素D和Src通路。几项第二阶段的研究正在进行中。前列腺癌相关转移性骨病的高发促使人们考虑将这一途径作为治疗靶点。为此，已经对几种骨靶向药物进行了研究，其中最引人注目的是唑来膦酸，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denosumab已经被开发出来用于骨转移的治疗。
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, similar to 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-beta ligand (RANKL) inhibitor, denosumab, has been developed for the treatment of bone metastases.