Therapeutic options for hormone-refractory prostate cancer in 2007
Therapeutic options for hormone-refractory prostate cancer in 2007
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DOI：
10.1016/j.urolonc.2007.05.010
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发表时间：
2007-09-01
影响因子：
2.7
通讯作者：
Gleave, Martin E.
中科院分区：
文献类型：
--
作者：
Hadaschik, Boris A.;Gleave, Martin E.
前列腺癌是美国男性中最常被诊断出的癌症，也是一个重大的健康问题。虽然局限性疾病有很好的治愈机会，但转移性疾病会在几年内导致雄激素非依赖性进展并死亡。尽管多西他赛是一个重要的治疗里程碑，是目前转移性激素难治性前列腺癌（HRPC）的标准治疗方法，但由于对治疗耐药细胞的克隆选择或具有耐药表型细胞的产生，大多数患者最终病情仍会进展。通过了解对雄激素剥夺和化疗耐药的分子基础，合理设计靶向治疗是可能的。在过去几年中，许多调节细胞凋亡、增殖和细胞信号传导的基因靶点已被确定，并且许多新型化合物作为单一药物或与细胞毒性化疗联合已进入临床试验。尤其应进一步鼓励新辅助试验，因为它们可以检测前列腺切除标本中的生物活性。本文综述了晚期前列腺癌男性患者可用的新治疗选择。尽管HRPC仍然无法治愈，但并非无法治疗。最近的研究结果非常有前景，但在Ⅲ期试验中证明有效的抗肿瘤活性以及显示出具有临床意义的生存益处方面仍然存在挑战。（C）2007爱思唯尔公司。保留所有权利。
Prostate cancer is the most commonly diagnosed cancer in American men and a major health problem. While localized disease has an excellent chance for cure, metastatic disease leads to androgen-independent progression and death within a few years. Although docetaxel represents an important therapeutic milestone and is the current standard of care for metastatic hormone-refractory prostate cancer (HRPC), most patients eventually progress because of clonal selection of therapy-resistant cells or the development of cells with a drug-resistant phenotype. By understanding the molecular basis of resistance to androgen withdrawal and chemotherapy, the rational design of targeted therapeutics is possible. Over the last few years, many gene targets that regulate apoptosis, proliferation, and cell signalling have been identified, and numerous novel compounds have entered clinical trials either as single agents or in combination with cytotoxic chemotherapy. Neoadjuvant trials in particular must be further encouraged since they allow detection of biological activity in the prostatectomy specimen. This article reviews new treatment options available for men with advanced prostate cancer. Even though HRPC remains incurable, it is not untreatable. Recent findings are very promising, but challenges remain in demonstrating effective anti-tumor activity and showing a clinically relevant survival benefit in Phase III trials. (C) 2007 Elsevier Inc. All rights reserved.