Heckmayr M
Zentrum für Pneumologie und Thoraxchirurgie Krankenhaus Grosshansdorf.
Pneumologie. 2004 Jun;58(6):408-15. doi: 10.1055/s-2004-818501.
Despite improvements in the early detection of lung tumors, mortality from this type of disease is increasing world wide and the 5-year-survival rate still ranges below 10 %. The approach of chemoprevention offers the possibility to interfere with the process of cancerogenesis by the use of natural or synthetic chemical compounds and either to prevent DNA damage or to stepp the proliferation of premalignant cells that are already in place. With regard to bronchial carcinoma, chemoprevention in the first place implies cessation of smoking but the currently used procedures are not extremely efficient and many ex-smokers experience an increased risk of acquiring a lung tumor over a prolonged period of time (secondary prevention). In the past 20 years many details of the process of tumorigenesis have been revealed and this knowledge has promoted the targeted use of chemopretective compounds. In addition to the classics in the fields, such as vitamin A, beta-carotene, vitamins E, C and B12 as well as selenium, the last years have brought the development of new compounds, such as retinoids, dithiols, cyclooxygenase inhibitors, epidermal growth factors and others, the mechanismen of action of which provide interesting new approaches. In addition, the introduction of biomarkers, either genetic alterations or proliferation or differentiation, allows to monitor the process of tumorigenesis in its different stages, from early to late, and thereby offers the perspective to perform studies on chemoprevention more rapidly and effectively as in previous years. Thus, in combination with optimized, controlled study designs it is to be expected that in near future clinical studies on the effects on chemoprotective compounds will yield decisive data on their efficacy in chronic smokers as well as ex-smokers.
尽管在肺癌早期检测方面有所改善,但这种疾病的全球死亡率仍在上升,5年生存率仍低于10%。化学预防方法提供了通过使用天然或合成化合物来干扰癌症发生过程的可能性,既可以防止DNA损伤,也可以阻止已经存在的癌前细胞的增殖。对于支气管癌,化学预防首先意味着戒烟,但目前使用的方法效率并不高,许多戒烟者在很长一段时间内患肺癌的风险增加(二级预防)。在过去20年里,肿瘤发生过程的许多细节已经被揭示,这些知识促进了化学预防化合物的靶向使用。除了该领域的经典物质,如维生素A、β-胡萝卜素、维生素E、C和B12以及硒之外,近年来还开发了新的化合物,如类视黄醇、二硫醇、环氧化酶抑制剂、表皮生长因子等,其作用机制提供了有趣的新方法。此外,引入生物标志物,无论是基因改变、增殖还是分化,都可以监测肿瘤发生从早期到晚期的不同阶段的过程,从而提供了比前几年更快、更有效地进行化学预防研究的前景。因此,结合优化的、受控的研究设计,可以预期在不久的将来,关于化学保护化合物作用的临床研究将产生关于其对慢性吸烟者和戒烟者疗效的决定性数据。