Östrogenrezeptoren und ihre Bedeutung für die Prognose und Therapie des Lungenkarzinoms – neue Erkenntnisse zu einem bisher unterschätzten Mechanismus

Zusammenfassung

Der Hauptrisikofaktor für die Entstehung von Lungenkarzinomen ist das Tabakrauchen, jedoch erkranken zunehmend auch Nichtraucher an dieser Erkrankung, insbesondere Frauen. Man geht davon aus, dass Sexualhormonrezeptoren, insbesondere der Östrogenrezeptor (ER), analog zum Mammakarzinom, bei den nicht-kleinzelligen Karzinomen der Lungen (NSCLC) eine zunehmende, bisher unterschätzte Rolle spielen. So gibt es schon länger indirekte Hinweise, dass die Behandlung mit Hormonen im Rahmen einer Hormonersatztherapie während der Menopause das Lungenkarzinomrisiko erhöht. Aber auch Untersuchungen an Zelllinien, Xenograft-Modellen und an menschlichen Tumoren von beiden Geschlechtern können mittlerweile die Expression von ER und ihre Bedeutung in der Proliferation des NSCLCs klar belegen. Analog zum Mammakarzinom scheint dem ER-Signalweg auch eine prognostische und prädiktive Funktion zuzukommen. Darüber hinaus kennt man neuerdings ein intrazelluläres Zusammenspiel des ER mit dem epithelialen Wachstumsfaktorrezeptor (EGFR). Letzterer ist eine wichtige Zielstruktur in der medikamentösen Therapie des NSCLC mit Tyrosinkinaseinhibitoren (TKI), wie etwa Gefitinib, Erlotinib oder Afatinib. Derzeit laufen erste klinische Studien, die Kombinationstherapien aus EGFR TKI mit antihormonellen Medikamenten, wie etwa dem Fulvestrant, beim NSCLC untersuchen.

Abstract

Though tobacco smoking is the leading cause of lung cancer, during the last decades the prevalence increased in never smoking patients, especially in women. Sex steroid hormones and particularly the estrogen receptors (ERs) seem to play an important but still underestimated role in non-small cell lung cancer (NSCLC). Beside long existing hints that hormone replacement therapy (HRT) increases the risk of lung tumors recent analyses on cell lines, xenografts and human tumors of both sexes gave clear evidence of ER expression and proliferation in NSCLC. Most recently, the expression of ERs apparently has prognostic and predictive value. Recently, an intracellular „cross-talk“ between the ER and the epithelial growth factor receptor (EGFR) could be demonstrated. EGFR are important targets of approved tyrosinkinases (TKIs), like gefitinib, erlotinib or afatinib. Currently, clinical studies are enrolling lung tumor patients for combination treatment with EGFR TKI and antihormonal drugs, e. g. fulvestrant.

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