Lippman S M, Spitz M R
Departments of Clinical Cancer Prevention, Thoracic/Head and Neck Medical Oncology, and Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
J Clin Oncol. 2001 Sep 15;19(18 Suppl):74S-82S.
Lung cancer is the leading cause of cancer deaths in the United States and the world, with grim incidence and mortality figures underscoring the need for new approaches, such as chemoprevention, for controlling this disease. There have been definitive, randomized, controlled lung-cancer chemoprevention trials in the three chemoprevention trial settings: primary (healthy high-risk [eg, smokers]), secondary (premalignant lesions), and tertiary (prevention of second primary tumors in previously treated patients), all of which produced negative (either neutral or harmful) primary end point results. These trials established that lung cancer was not prevented by alpha-tocopherol, beta-carotene, retinol, retinyl palmitate, N-acetylcysteine, or isotretinoin in smokers. Provocative leads of the definitive trials include the possible activity of isotretinoin in never and former smokers and that of alpha-tocopherol in prostate cancer prevention. A major area of lung cancer research is molecular epidemiologic study of highest smoking-related risk based on the interactions between tobacco carcinogens, genetic polymorphisms involved in activating and detoxifying these carcinogens, and host-cell efficiency in monitoring and repairing tobacco carcinogen-DNA damage. The future of lung cancer chemoprevention will rely heavily on molecular studies of carcinogenesis and drug mechanisms to develop novel chemopreventive targets and drugs, risk markers, and surrogate end point biomarkers; new preclinical drug-testing models; novel imaging techniques for monitoring agent activity; and molecular epidemiologic risk models for identifying the highest-risk current and former smokers.
肺癌是美国和全球癌症死亡的主要原因，严峻的发病率和死亡率数据凸显了采用新方法（如化学预防）来控制这种疾病的必要性。在三种化学预防试验环境中已开展了明确的、随机对照的肺癌化学预防试验：一级预防（健康的高危人群[如吸烟者]）、二级预防（癌前病变）和三级预防（预防先前接受治疗患者的第二原发性肿瘤），所有这些试验的主要终点结果均为阴性（中性或有害）。这些试验证实，α-生育酚、β-胡萝卜素、视黄醇、棕榈酸视黄酯、N-乙酰半胱氨酸或异维甲酸并不能预防吸烟者患肺癌。这些确定性试验中引人关注的线索包括异维甲酸在从不吸烟和曾经吸烟人群中可能具有的活性，以及α-生育酚在预防前列腺癌方面的活性。肺癌研究的一个主要领域是基于烟草致癌物、参与激活和解毒这些致癌物的基因多态性以及宿主细胞监测和修复烟草致癌物-DNA损伤的效率之间的相互作用，对与吸烟相关的最高风险进行分子流行病学研究。肺癌化学预防的未来将严重依赖于癌症发生机制和药物作用机制的分子研究，以开发新的化学预防靶点和药物、风险标志物以及替代终点生物标志物；新的临床前药物测试模型；用于监测药物活性的新型成像技术；以及用于识别当前和曾经吸烟的高危人群的分子流行病学风险模型。
