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Antikörpertherapie in klinischer und präklinischer Anwendung bei gastrointestinalen Karzinomen

Antibody therapy in the clinical and preclinical treatment of gastrointestinal cancer

  • Leitthema
  • Published:
Der Onkologe Aims and scope

Zusammenfassung

Derzeit befinden sich viele neue Substanzen zur Therapie gastrointestinaler Karzinome in klinischer und präklinischer Anwendung. Die Apoptose von malignen Zellen als natürliche Form der Zellzerstörung stellt ein ideales Ziel in der Krebstherapie dar. Die tatsächliche Effektivität und das Nebenwirkungsspektrum bisheriger Antikörper sind gegenwärtig von einer überzeugenden klinischen Anwendung zu weit entfernt. Verschiedene Substanzklassen von Antikörpern geben aber Hoffnung, dass in naher Zukunft die Verträglichkeit durch veränderte Herstellung (Humanisierung, Chimärisation oder komplett humane Antikörper) und die Wirkung durch höhere Selektivität substanziell verbessert werden.

Durch den Einsatz neuer Zytostatika und die Entwicklung zielgerichteter Antikörper gegen EGFR und VEGF konnte das mediane Überleben bei Patienten mit gastrointestinalen Karzinomen in den letzten Jahren deutlich verlängert werden. Insbesondere das Überleben von Patienten mit fortgeschrittenen kolorektalen Karzinomen konnte auf aktuell über 2 Jahre verlängert und damit im Vergleich zur 5-FU-Ära fast verdoppelt werden. Die vielfältigen Kombinationstherapien mit Chemotherapeutika und monoklonalen Antikörpern machen die Behandlung von Patienten mit gastrointestinalen Karzinomen zwar deutlich komplexer als früher, bieten aber gerade Patienten mit Metastasen wesentlich effektivere Therapieansätze. Bevacizumab und Cetuximab als Paradebeispiele der „targeted therapy“ haben innerhalb klinischer Studien in der Erst- und Zweitlinientherapie des metastasierten kolorektalen Karzinoms berechtigterweise Einzug gehalten.

Abstract

The clinical and preclinical applications of new antitumor agents for the treatment of gastrointestinal cancer is a field undergoing continuous progress. The antibody derived apoptosis of tumor cells represents an ideal target in cancer therapy. However, the actual effectiveness of and tolerance to antibodies does not yet allow for a convincing clinical application. Modifications in the production of antibodies, such as humanisation, chimerisation or the establishment of totally human antibodies, provide hope for higher selectivity and less side effects in the future.

Through the development of targeted therapy with antibodies against epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), as well as the combination with new cytotoxic agents, the median overall survival in colorectal cancer patients has been significantly improved over the next few years. In particular, the survival of patients with advanced colorectal cancer could be increased by more than 2 years, almost doubling that found with the classical 5-FU regimen. Thus, the use of chemotherapy and antibodies in the treatment of gastrointestinal cancer means that this has become not only more effective, particularly for patients with metastases, but also much more complex. Bevacizumab and cetuximab are excellent examples for a selectively targeted therapy in first and second-line therapy for metastatic colorectal cancer.

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  1. Zentrum Operative Medizin, Chirurgische Klinik I, Universitätsklinikum Würzburg, Oberdürrbacherstraße 6, 97080, Würzburg, Deutschland

    A. Thalheimer, A. Thiede, D. Meyer & B. Illert

  2. Pathologisches Institut, Universitätsklinikum Würzburg, Würzburg, Deutschland

    S. Braendlein & P. Vollmers

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  1. A. Thalheimer
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Thalheimer, A., Braendlein, S., Vollmers, P. et al. Antikörpertherapie in klinischer und präklinischer Anwendung bei gastrointestinalen Karzinomen. Onkologe 13, 236–249 (2007). https://doi.org/10.1007/s00761-007-1190-3

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