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Zielgerichtete Therapieansätze beim Endometriumkarzinom

Targeted therapy approach for endometrial cancer

  • Leitthema
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Zusammenfassung

Endometriumkarzinome (EC) sind eine heterogene Gruppe von malignen epithelialen Neoplasien mit sowohl unterschiedlichen Ätiologien, histopathologischen und molekularen Eigenschaften als auch einem breiten Spektrum an klinischen Verläufen. Im Rahmen der Primärbehandlung einer lokalisierten Erkrankung stellt die operativ-chirurgische Entfernung der inneren Genitalien der Frau die entscheidende Basistherapie für die überwiegende Mehrzahl der Patientinnen dar, anhand derer ggf. der Einsatz zusätzlicher adjuvanter Maßnahmen je nach Risikoprofil vorgenommen werden können. Die Behandlung im Falle einer disseminierten Erkrankung hingegen besteht aktuell aus der Durchführung konventioneller Chemotherapien und/oder antihormoneller Therapiestrategien. Jüngste Erkenntnisse im Verständnis der molekularen Pathologie der heutzutage allgemein anerkannten 2 Haupttypen des EC – Typ 1 (endometrioid) und Typ 2 (nichtendometrioid) – haben die ersten Schritte in der Entwicklung und Erprobung von zielgerichteten Therapieansätzen in der Behandlung des disseminierten EC geebnet. Von den aktuell identifizierten potenziell therapeutischen Targets liegen zurzeit lediglich mäßig erfolgreiche Ergebnisse aus einigen klinischen Phase-II-Studien vor, welche entweder auf einer Inhibition der mTOR-Signalkaskade, einer Hemmung diverser Wachstumsfaktoren (z. B. EGFR bzw. VEGF) oder aber auf einer Immuntherapie mit einem monoklonalen Antikörper gegen HER2-NEU beruhen. Trotz der markanten molekularen Unterschiede zwischen Typ-1- und Typ-2-Endometriumkarzinomen haben die meisten klinischen Studien diese Diversität bislang nicht hinreichend berücksichtigt.

Abstract

Endometrial cancer comprises a heterogeneous group of malignant epithelial tumors with different etiologies, distinct histopathological and molecular characteristics as well as a variety of clinical presentations. At primary diagnosis of localized disease, hysterectomy and salpingoophorectomy represent the current gold standard of initial treatment and the decision about further adjuvant therapy is based on an individual histopathological risk profile. Currently, treatment of metastatic disease is based on conventional chemotherapy or anti-proliferative hormonal agents. Recent advances in the understanding of the different molecular pathologies of the two types of endometrial cancer have underlined initial steps in the development and testing of targeted therapies. Of the potential therapeutic targets identified to date, clinical trials have assessed the efficacy of mTOR inhibitors, inhibition of several growth factors (mainly EGRF and VEGF) or treatment with monoclonal antibodies against HER2-new, all of which have shown only modest success. Despite the known diversity between type I and II cancers, the vast majority of clinical trials have not taken these differences into account.

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Authors and Affiliations

  1. Gynäkologie und Geburtshilfe, Hochtaunus-Kliniken Bad Homburg, Urseler Straße 33, 61348, Bad Homburg, Deutschland

    D. Denschlag

  2. Frauenklinik, Universitätsklinikum Erlangen, Erlangen, Deutschland

    M.W. Beckmann

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  2. M.W. Beckmann
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Denschlag, D., Beckmann, M. Zielgerichtete Therapieansätze beim Endometriumkarzinom. Onkologe 18, 891–900 (2012). https://doi.org/10.1007/s00761-012-2293-z

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