2-Methoxyestradiol als neue Substanz zur Krebstherapie

Zusammenfassung

2-Methoxyestradiol (2-ME2) ist ein physiologischer Östrogenmetabolit, der das Wachstum vieler verschiedener Tumortypen hemmt. Viele Wirkmechanismen sind beschrieben worden. Neben einem starken antiangiogenetischen und proapoptotischen Effekt gibt es weitere wichtige Wirkungen wie die Hemmung der Mikrotubuli während der Mitose und die Hemmung des Hypoxia-Inducible-Factor 1α (HIF-1 α). Multiresistente Tumorzellen auf Zytostatika zeigten sich komplett sensibel gegenüber der Behandlung mit 2-ME2. Studien mit hohen Dosen 2-ME2 ergaben, dass die Nebenwirkungen auf gesunde Zellen und Organe minimal waren. Aufgrund der experimentellen Ergebnisse wurden verschiedene klinische Studien bei Patienten mit verschiedenen Tumoren initiiert. Wir fassen hier die wichtigsten tumorhemmenden Wirkungen von 2-ME2 sowie die Darstellung der aktuellen Studien zusammen.

Summary

2-Methoxyestradiol (2-ME2), a physiological metabolite of estrogen, inhibits the growth of different tumor types. Many mechanisms of action have been described. In addition to a strong antiangiogenic effect and induction of apoptosis, there are other important mechanisms, such as the inhibition of microtubules during mitosis or the inhibition of the hypoxia-inducible-factor 1α (HIF1 α). Multidrug-resistant cancer cells appear to be highly sensitive to 2-ME2. Studies with high dosage 2-ME2 have shown that there are only minimal reversible side effects on normal tissue. The experimental data on human tumors have led to the initiation of several clinical trials with promising results. We here summarize the effect of 2-ME2 on various tumor types in vitro and in vivo, as well as the initial results of current clinical trials.

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