Bosland Maarten C, McCormick David L, Melamed Jonathan, Walden Paul D, Zeleniuch-Jacquotte Anne, Lumey L H
Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Eur J Cancer Prev. 2002 Aug;11 Suppl 2:S18-27.
Prostate cancer is the most common male malignancy in western countries. Although primary prevention of prostate cancer is not possible, screening using prostate-specific antigen (PSA) may eliminate prostate cancers by definitive treatments. Prevention of clinically detectable prostate cancer requires earlier chemoprevention interventions. Because prostate cancer is histologically present in 30-50% of 30- to 50-year-old men, effective chemoprevention needs to inhibit not only prostate carcinogenesis but also growth and progression of these cancers. A prostate carcinogenesis animal model has been used to screen chemopreventive agents; inhibitory effects were found with 9-cis-retinoic acid, dehydroepiandrosterone, fluasterone, and the Bowman-Birk inhibitor and an isoflavone mixture which both occur in soy. Such results can be used to select agents for clinical trials. Besides large-scale long-duration prevention trials, trials of short/intermediate duration using smaller cohorts prior to or following radical prostatectomy may provide excellent and cost-effective approaches for chemopreventive agent efficacy testing. Intervention prior to surgery allows measurements of intervention agents and intermediate end-points in the prostate. These peri-surgical trials only assess inhibition of growth and progression of preexisting cancer, not real preventive effects, but they focus on clinically significant cancers. Such trials are an essential step in the development of antiprostate cancer chemoprevention agents.
前列腺癌是西方国家最常见的男性恶性肿瘤。虽然前列腺癌的一级预防是不可能的，但使用前列腺特异性抗原（PSA）进行筛查可能通过确定性治疗消除前列腺癌。预防临床可检测的前列腺癌需要更早的化学预防干预措施。由于在30至50岁的男性中，30%-50%在组织学上存在前列腺癌，有效的化学预防不仅需要抑制前列腺癌的发生，还需要抑制这些癌症的生长和进展。一种前列腺癌发生动物模型已被用于筛选化学预防剂；发现9-顺式视黄酸、脱氢表雄酮、氟睾酮、鲍曼-伯克抑制剂以及大豆中含有的一种异黄酮混合物具有抑制作用。这些结果可用于选择进行临床试验的药物。除了大规模长期预防试验外，在根治性前列腺切除术之前或之后使用较小队列进行的短期/中期试验可能为化学预防剂疗效测试提供优秀且具有成本效益的方法。手术前的干预可以测量前列腺中的干预药物和中间终点。这些围手术期试验仅评估对已存在癌症的生长和进展的抑制作用，而非真正的预防效果，但它们关注具有临床意义的癌症。此类试验是抗前列腺癌化学预防剂研发的重要一步。
