Greenwald Peter
Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7309, USA.
Recent Results Cancer Res. 2007;174:3-17. doi: 10.1007/978-3-540-37696-5_1.
Clifton Leaf, in his article "Why We're Losing the War on Cancer," presents criticisms of past research approaches and the small impact of this research thus far on producing cures or substantially extending the life of many cancer patients. It is true that gains in long-term survival for people with advanced cancers have been modest, hindered in part by the heterogeneity of tumors, which allows the cancers to persist using alternate molecular pathways and so evade many cancer therapeutics. In contrast, clinical trials have demonstrated that it is possible to reduce the incidence or improve cancer survival through prevention and early detection. Strides have been made in preventing or detecting early the four deadliest cancers in the United States (i.e., lung, breast, prostate, and colorectal). For example, 7-year follow-up data from the Breast Cancer Prevention Trial (BCPT) provides evidence that tamoxifen reduces the occurrence of invasive breast tumors by more than 40%; recent studies using aromatase inhibitors and raloxifene are also promising. The Prostate Cancer Prevention Trial (PCPT) showed that finasteride reduced prostate cancer incidence by 25%, and the ongoing Selenium and Vitamin E Cancer Prevention Trial (SELECT) is investigating selenium and vitamin E for prostate cancer prevention based on encouraging results from earlier studies. Living a healthy lifestyle, including regular physical activity, avoiding obesity, and eating primarily a plant-based diet has been associated with a lower risk of colorectal cancer. In addition, noninvasive stool DNA tests for early detection are being studied, which may lessen the reluctance of people to be screened for colorectal polyps and cancer. Behavioral and medical approaches for smoking prevention are ways to reduce the incidence of lung cancer, with antinicotine vaccines on the horizon that may help former smokers to avoid relapse. The US National Lung Screening Trial is testing whether early detection via spiral CT screening will reduce lung cancer mortality. Prevention and earlier detection offer efficient and practical strategies to reduce the cancer burden. Several of the suggestions Mr. Leaf makes, such as developing interdisciplinary collaborations and allocating resources to research earlier in the process of carcinogenesis, have become an integral strategy in the National Cancer Institute's (NCI) approach in the past decade, specifically in the realm of cancer prevention and early detection. For example, an aggressive program to identify biomarkers for earlier detection of cancer--the NCI's Early Detection Research Detection (EDRN)--has identified three promising biomarkers since its establishment in 2000. It collaborates with the National Institute of Standards and Technology and extramural scientists to develop validation standards and to identify the best technologies to use for systematic investigations. If these biomarkers can be validated, they might help to reduce cancer mortality.
克利夫顿·利夫在其文章《为何我们在抗癌之战中失败》中，批评了过去的研究方法，以及迄今为止该研究在研发治愈方法或大幅延长许多癌症患者生命方面产生的微小影响。的确，晚期癌症患者的长期生存率虽有一定提高，但幅度不大，部分原因是肿瘤的异质性，这使得癌症能够通过其他分子途径持续存在，从而逃避许多癌症治疗方法。相比之下，临床试验表明，通过预防和早期检测来降低癌症发病率或提高癌症生存率是可行的。在美国，在预防或早期检测四种最致命的癌症（即肺癌、乳腺癌、前列腺癌和结直肠癌）方面已经取得了进展。例如，乳腺癌预防试验（BCPT）的7年随访数据表明，他莫昔芬可使浸润性乳腺肿瘤的发生率降低40%以上；最近使用芳香化酶抑制剂和雷洛昔芬的研究也很有前景。前列腺癌预防试验（PCPT）表明，非那雄胺可使前列腺癌发病率降低25%，而正在进行的硒和维生素E癌症预防试验（SELECT）基于早期研究的鼓舞人心的结果，正在研究硒和维生素E对前列腺癌的预防作用。保持健康的生活方式，包括定期进行体育锻炼、避免肥胖以及主要以植物性饮食为主，与降低结直肠癌风险相关。此外，正在研究用于早期检测的非侵入性粪便DNA检测方法，这可能会减少人们对接受结直肠息肉和癌症筛查的抵触情绪。预防吸烟的行为和医学方法是降低肺癌发病率的途径，有望出现的抗尼古丁疫苗可能有助于戒烟者避免复吸。美国国家肺癌筛查试验正在测试通过螺旋CT筛查进行早期检测是否会降低肺癌死亡率。预防和早期检测为减轻癌症负担提供了有效且实用的策略。利夫先生提出的一些建议，比如开展跨学科合作以及在致癌过程的早期阶段就为研究分配资源，在过去十年中已成为美国国立癌症研究所（NCI）方法中的一项不可或缺的策略，特别是在癌症预防和早期检测领域。例如，一项旨在识别用于癌症早期检测的生物标志物的积极计划——NCI的早期检测研究网络（EDRN）——自2000年成立以来已经识别出三种有前景的生物标志物。它与美国国家标准与技术研究院及校外科学家合作，制定验证标准，并确定用于系统研究的最佳技术。如果这些生物标志物能够得到验证，它们可能有助于降低癌症死亡率。
