Bosland Maarten C
Department of Pathology, University of Illinois at Chicago, Chicago, Illinois.
Cancer Prev Res (Phila). 2016 Aug;9(8):642-7. doi: 10.1158/1940-6207.CAPR-16-0088. Epub 2016 Apr 20.
The outcome of the Selenium and Vitamin E Cancer Prevention Trial, demonstrating harm and no preventive activity of selenomethionine and α-tocopherol for prostate cancer, and the lack of approval by the FDA for the use of 5α-reductase inhibitors to prevent prostate cancer have cast doubt about the future of chemoprevention of prostate cancer. This article attempts to critically assess whether the notion that chemoprevention of prostate cancer has no future is warranted. Risk of prostate cancer is modifiable and chemoprevention of prostate cancer, particularly fatal/lethal cancer, is both needed and possible. However, the approach to prostate cancer-chemopreventive agent development has not followed a rational and systematic process. To make progress, the following steps are necessary: (i) identification of intermediate biomarkers predictive of fatal/lethal disease; (ii) development of a rational approach to identification of candidate agents, including high-throughput screening and generation of information on mechanism and biology of candidate agents and potential molecular targets; and (iii) systematic evaluation of the predictive value of preclinical models, phase II trials, and intermediate biomarkers for the outcome of phase III trials. New phase III trials should be based on adequate preclinical and phase II studies. Cancer Prev Res; 9(8); 642-7. ©2016 AACR.
硒和维生素E癌症预防试验的结果表明，硒代蛋氨酸和α-生育酚对前列腺癌并无预防作用反而有害，且美国食品药品监督管理局未批准使用5α-还原酶抑制剂预防前列腺癌，这使得前列腺癌化学预防的前景受到质疑。本文试图批判性地评估“前列腺癌化学预防没有未来”这一观点是否合理。前列腺癌风险是可以改变的，对前列腺癌尤其是致命性前列腺癌进行化学预防是必要且可行的。然而，前列腺癌化学预防药物的研发方法并未遵循合理且系统的流程。为取得进展，需要采取以下步骤：（i）识别预测致命性/致死性疾病的中间生物标志物；（ii）制定合理的方法来识别候选药物，包括高通量筛选以及生成关于候选药物的作用机制、生物学特性和潜在分子靶点的信息；（iii）系统评估临床前模型、II期试验以及中间生物标志物对III期试验结果的预测价值。新的III期试验应基于充分的临床前和II期研究。《癌症预防研究》；9(8)；642 - 647。©2016美国癌症研究协会。
