Hadaschik Boris A, Gleave Martin E
The Prostate Centre at Vancouver General Hospital, Vancouver, British Columbia, Canada.
Urol Oncol. 2007 Sep-Oct;25(5):413-9. doi: 10.1016/j.urolonc.2007.05.010.
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.
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，但转移性疾病会导致雄激素非依赖性进展，并在几年内导致死亡。尽管多西他赛代表了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，但大多数患者最终仍会进展，原因是治疗耐药细胞的克隆选择或具有耐药表型的细胞的出现。通过了解对雄激素剥夺和化疗耐药的分子基础，有可能合理设计靶向治疗药物。在过去几年中，已经确定了许多调节细胞凋亡、增殖和细胞信号传导的基因靶点，并且许多新型化合物已经作为单一药物或与细胞毒性化疗联合进入临床试验。尤其必须进一步鼓励新辅助试验，因为它们能够在前列腺切除标本中检测生物活性。本文综述了晚期前列腺癌男性可用的新治疗选择。尽管HRPC仍然无法治愈，但并非不可治疗。最近的研究结果很有前景，但在III期试验中证明有效的抗肿瘤活性并显示出临床相关的生存获益方面仍存在挑战。
