Adenokarzinome des Magens und des ösophagogastralen Übergangs – Personalisierte Systemtherapie

Adenokarzinome des Magens und des ösophagogastralen Übergangs (ÖGÜ) sind die zweithäufigste Todesursache weltweit. Trotz der Fortschritte im Bereich der Behandlungsmöglichkeiten ist die Verbesserung des Überlebens, mit einem medianen Überleben von weniger als einem Jahr in der metastasierten Erkrankungssituation weiterhin unbefriedigend. In Zeiten intensiver translationaler Forschung und zunehmend personalisierter Therapie ist die Suche nach neuen prädiktiven und diagnostischen Zielstrukturen damit unverändert von großer klinischer Relevanz.

Bei Patienten mit einem Her-2/neu überexprimierenden oder amplifizierten Karzinom führt die Behandlung mit Trastuzumab in Kombination mit Chemotherapie zu einer Verbesserung des medianen Überlebens. Bislang waren allerdings, abgesehen von der Therapie gegen Her-2 überexprimierende Tumore, alle Ergebnisse zu zielgerichteten Therapien enttäuschend. Molekulare Zielstrukturen, die derzeit in unterschiedlichen Phase-II- und -III-Studien evaluiert werden, sind der epidermale Wachstumsfaktor (EGFR) mit den Subtypen ERBB-1, ERBB-2 (Her-2/neu), ERBB-3 und ERBB-4, der vaskuläre endotheliale Wachstumsfaktor (VEGF) und seine Rezeptoren (VEGFR), das mammalian target of Rapamycin (mTOR) sowie Antikörper gegen den Tyrosinkinaserezeptor c-Met.

Gastroesophageal cancer is the second leading cancer cause of death globally. Despite having improved treatment modalities over the last decade, for most patient's only modest improvements have been seen in overall survival with a median survival below one year. Therefore, in the era of intense translational research and personalized therapy, the identification of novel predictive and diagnostic targets is urgently needed.

Patients with Her-2 overexpression or amplification have experienced significant gains in overall survival with the treatment of Trastuzumab in addition to chemotherapy. However, apart from the successful targeting of Her-2 overexpression in gastroesophageal cancer with Trastuzumab, other targeted therapies have fallen short. The molecular targets currently being evaluated in various phase II and III clinical trials include the epidermal derived growth factor receptor (EGFR) with subtypes ERBB-1, ERBB-2 (Her-2/neu), ERBB-3 and ERBB-4, vascular endothelial derived growth factor (VEGF) and its receptor (VEGFR), mammalian target of Rapamycin (mTOR) and antibodies against the tyrosinkinase receptor c-Met.

Key words

Gastroesophageal cancer - targeted therapy - Her-2 - Trastuzumab

• Literatur

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