Chemoprävention beim Bronchialkarzinom: Überblick über bisherige Studien, Ergebnisse und zukünftige Entwicklungen

Zusammenfassung

Trotz verbesserter Früherkennungsmaßnahmen beim Bronchialkarzinom steigen die Mortalitätsraten weltweit und die 5-Jahres-Überlebensrate liegt weiterhin unter 10 %. Mit der Chemoprävention besteht die Möglichkeit, mit Hilfe natürlicher oder synthetischer Substanzen in den Prozess der Kanzerogenese so einzugreifen, dass entweder die Schädigung der DNA verhindert oder aber die Proliferation bereits vorhandener prämaligner Zellen unterbunden wird. Chemoprävention beim Bronchialkarzinom bedeutet zwar primär Aufgabe des Nikotinkonsums, viele Ex-Raucher sind aber über einen längeren Zeitraum weiterhin einem erhöhten Karzinomrisiko ausgesetzt (sekundäre Prävention). In den letzten 20 Jahren sind detaillierte Kenntnisse über den Mechanismus der Karzinogenese bekannt geworden, die den gezielten Einsatz von Chemoprotektiva erleichtern. Neben den klassischen Chemoprotektiva, zu denen Vitamin A, β-Carotin, die Vitamine E, C und B12 ebenso wie Selen gehören, wurden in den letzten Jahren neuere Substanzen entwickelt, wie die Retinamide als synthetische Verbindungen des Vitamin A, Dithiole, Cyclooxygenase-Inhibitoren, epidermale Wachstumsfaktoren u. a., deren Mechanismen interessante Ansatzpunkte der Chemoprävention liefern. Die Entwicklung von Biomarkern (Genom-, Proliferations- und Differenzierungsmarker), mit deren Hilfe verschiedenen Phasen im Prozess der Krebsentstehung verfolgt werden können, erlaubt es, Studien zur Prävention schneller und effektiver durchzuführen. Nach Optimierung entsprechender Studiendesigns ist zu hoffen, dass in absehbarer Zeit klinische Studien mit Chemoprotektiva effizient bei chronischen Rauchern und Ex-Rauchern durchgeführt werden können.

Abstract

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, β-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.

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