文章：

癌症预防目标的选择：我们将何去何从？

Selecting targets for cancer prevention: where do we go from here?

原文发布日期：2006-10-12

DOI: 10.1038/nrc2008

类型: Review Article

开放获取: 否

要点：

1. The selection of agents for cancer prevention requires a thorough understanding of the potential efficacy and toxicities that are associated with specific agents.
2. Evidence of effectiveness for prevention comes from a knowledge of mechanisms, in vitro and animal in vivo experimental data, epidemiological case–control and cohort studies, and data from clinical trials (both early-phase cancer prevention trials and secondary endpoint analysis of trials performed for other indications).
3. Risk–benefit considerations are crucial to the choice of agents for cancer prevention. The greater the risk of cancer, the greater the toxicity that is acceptable. There is a great need to improve risk-assessment tools to identify those individuals with the highest cancer risk who stand to gain the most benefit from preventive interventions.
4. Understanding the molecular mechanisms and the temporal sequence of events that result in carcinogenesis are crucial to the choice of agents and the design of prevention trials. Interventions need to target specific abnormalities when these abnormalities are crucial to cancer development.
5. New clinical trial designs are needed for efficient cancer preventive drug evaluation. Nesting 'prevention endpoints' into cancer treatment trials provides opportunities for the simultaneous development of agents for prevention and treatment if the toxicity profile of the agent is benign enough to warrant prevention applications.

要点翻译：

1. 癌症预防药物的选择需充分了解特定药物的潜在疗效与毒性。
2. 预防有效性的证据来源于对作用机制的认识、体外与动物体内实验数据、流行病学病例对照与队列研究，以及临床试验数据（包括早期癌症预防试验和针对其他适应症试验的次要终点分析）。
3. 风险-效益权衡对于癌症预防药物的选择至关重要。癌症风险越高，可接受的毒性范围就越大。当前亟需改进风险评估工具，以精准识别癌症风险最高的个体，使其能从预防性干预中获得最大收益。
4. 理解导致癌变的分子机制与事件时间顺序对药物选择及预防试验设计具有决定性意义。干预措施需针对那些对癌症发展至关重要的特定异常环节。
5. 需要新的临床试验设计以高效评估癌症预防药物。若药物的毒性特征足够安全，适合预防应用，将“预防终点”嵌入癌症治疗试验中，可为预防与治疗药物的同步研发提供契机。

英文摘要：

Given the lack of progress in curing metastatic epithelial cancers, there is intense interest in, and a sound scientific rationale for, pursuing strategies to prevent cancer. However, although several clinical trials have shown efficacy in cancer prevention, few have resulted in changes to medical practice, and some trials have even shown harm. Recent experiences with serious side effects identified in cancer prevention trials underscore the need to re-evaluate our approach to clinical chemopreventive drug development, and to establish a framework for agent selection for future trials.

摘要翻译： 

鉴于治愈转移性上皮癌的进展甚微，人们对癌症预防策略表现出极大兴趣，且这一方向具备坚实的科学基础。然而，尽管多项临床试验已证实癌症预防的效果，却很少能由此改变医疗实践，有些试验甚至显示出危害。近期在癌症预防试验中发现严重副作用的经历，促使我们重新评估临床化学预防药物开发的方法，并为未来试验的药物选择建立框架。

原文链接：

Selecting targets for cancer prevention: where do we go from here?