Greenwald Peter, Dunn Barbara K
National Cancer Institute NIH, Division of Cancer Prevention, Bethesda, MD 20892, USA.
Recent Results Cancer Res. 2009;181:3-17. doi: 10.1007/978-3-540-69297-3_1.
Three decades of intensive experimental and clinical research on cancer prevention have yielded an impressive body of scientific knowledge about cancer epidemiology, causation, and preventative measures. Despite our increased understanding in these critical areas, this knowledge is not being translated adequately into initiatives that will impact public health. The recent release of the World Cancer Research Fund/American Institute for Cancer Research report on diet and lifestyle strategies for cancer prevention--grounded in an evidence-based, systematic review of the published literature--is a strong acknowledgment of the benefits of a lifestyle approach to reduce cancer risk. The report also emphasizes the need to increase basic nutritional science research to make optimal use of the knowledge gained in the past three decades. Medical approaches--represented by chemoprevention clinical trials--also have become more focused based on results from basic science leads. The expansion of preclinical chemoprevention studies and greater attention to "first-in-human" prevention trials that safely shorten the timeline for new drug development are needed. The development of a prevention focus for what the U.S. Food and Drug Administration calls "exploratory investigational new drug studies" and what investigators at the National Cancer Institute are calling "phase 0" clinical trials will contribute to the decision-making involved in designing larger cancer prevention clinical trials. Past achievements in phase III prevention clinical trials--such as the Prostate Cancer Prevention Trial, the Breast Cancer Prevention Trial, and the Study of Tamoxifen and Raloxifene--have provided early successes as evidence of the potential for public benefit to be derived from this research. Nevertheless, the application of these findings to clinical practice and the design of future prevention trials remains a challenge. Current strategies include the refinement of risk assessment models for several major cancers. Additional initiatives, based on emerging basic and clinical research, involve the development of potential biomarkers for cancer risk and early detection by the National Cancer Institute's Early Detection Research Network. Although a recent progress report indicates that biomarkers of cancer susceptibility and exposure have been identified, continued work is needed to validate such markers for clinical use. Using this information optimally for prevention through lifestyle changes or medical interventions will demand commitments from public and private research institutions. Another area of emerging research is the development of a systems biology approach to cancer prevention. This will demand the creation of multidisciplinary teams of researchers from biological sciences, informatics and engineering scientists, and researchers from many fields not generally focused on disease prevention. To facilitate this and other new approaches, and to make effective use of information and strategies for cancer prevention, intensive training efforts must be implemented to develop the next generation of basic and clinical scientists--and physician researchers--capable of working in a cross- and multidisciplinary research environment. Training current researchers in new approaches will add efficiency to their combined research experiences.
三十年来,针对癌症预防开展了大量深入的实验研究和临床研究,积累了关于癌症流行病学、病因及预防措施的丰富科学知识。尽管我们在这些关键领域的认识有所提高,但这些知识尚未充分转化为能够影响公众健康的举措。世界癌症研究基金会/美国癌症研究学会近期发布了一份关于预防癌症的饮食和生活方式策略的报告——该报告基于对已发表文献的循证系统综述——有力地肯定了采用生活方式方法降低癌症风险的益处。报告还强调需要加强基础营养科学研究,以便充分利用过去三十年所取得的知识。以化学预防临床试验为代表的医学方法,也根据基础科学研究成果变得更加有的放矢。需要扩大临床前化学预防研究,并更加关注“首次人体”预防试验,这类试验能安全地缩短新药研发时间。为美国食品药品监督管理局所称的“探索性研究性新药研究”以及美国国立癌症研究所研究人员所称的“0期”临床试验确定预防重点,将有助于为设计更大规模的癌症预防临床试验提供决策依据。过去在III期预防临床试验中取得的成果——如前列腺癌预防试验、乳腺癌预防试验以及他莫昔芬与雷洛昔芬研究——已取得初步成功,证明了这项研究有望给公众带来益处。然而,将这些研究结果应用于临床实践以及设计未来的预防试验仍然是一项挑战。当前的策略包括完善几种主要癌症的风险评估模型。基于新出现的基础研究和临床研究的其他举措,涉及美国国立癌症研究所早期检测研究网络开发癌症风险及早期检测的潜在生物标志物。尽管最近的一份进展报告表明已确定了癌症易感性和暴露的生物标志物,但仍需继续开展工作以验证这些标志物在临床中的应用。要通过改变生活方式或进行医学干预,最佳地利用这些信息进行预防,公共和私营研究机构都需做出承诺。新兴研究的另一个领域是开发用于癌症预防的系统生物学方法。这将需要组建多学科研究团队,成员包括生物科学、信息学和工程学领域的科学家,以及许多通常不专注于疾病预防领域的研究人员。为推动这一方法及其他新方法的发展,并有效利用癌症预防的信息和策略,必须大力开展培训工作,培养能够在跨学科和多学科研究环境中工作的新一代基础和临床科学家以及医师研究人员。对现有研究人员进行新方法培训,将提高他们综合研究经验的效率。