Anti-Angiogenese: Von der präklinischen Forschung zur klinischen Anwendung

Zusammenfassung

Angiogenese, die Entwicklung neuer Blutgefäße, ist essenziell für das Wachstum und die Metastasierung von Tumoren. Es existieren ausreichend klinische Hinweise, die die zentrale Bedeutung der Angiogenese für die Tumorprogression beweisen. Die Hemmung der Angiogenese könnte somit die Behandlung von Patientinnen mit gynäkologischen Malignomen effektiver gestalten. Eine Vielzahl von möglichen therapeutischen „Targets“ antiangiogener Substanzen wurde bereits identifiziert. Es konnte gezeigt werden, dass die häufige Gabe bestimmter Chemotherapeutika in niedriger Dosierung, auch bekannt als „metronomische Chemotherapie“, antiangiogen wirkt. Der humanisierte monoklonale anti-VEGF-Antikörper Bevacizumab ist der gegenwärtig klinisch am weitesten ausgereifte Angiogenesehemmer. In einer klinischen Phase-III-Studie führte die Zugabe von Bevacizumab zu Paclitaxel in der First-Line-Behandlung von Patientinnen mit fortgeschrittenem Mammakarzinom zu einer signifikanten Verlängerung des progressionsfreien Überlebens. Diese Studie belegt somit die Effektivität einer antiangiogenen Therapie bei Brustkrebs. Weitere Studien mit Bevacizumab, zum Beispiel beim Ovarialkarzinom, laufen derzeit. Eine Vielzahl anderer Angiogeneseinhibitoren wird gegenwärtig klinisch untersucht, und neue angiogenesehemmende Substanzen werden entwickelt. Dieser Artikel gibt eine Übersicht über die Rolle der Gefäßneubildung bei der Pathogenese maligner Tumorerkrankungen sowie über aktuelle Behandlungsstrategien zur Hemmung der Tumorangiogenese.

Abstract

Angiogenesis, the process of new blood vessel formation, is required for tumor growth and metastasis. There is also substantial clinical evidence supporting the central role of angiogenesis in tumor progression. Thus, the inhibition of angiogenesis may provide more efficacious treatment for patients with advanced gynecological malignancies. A number of possible therapeutic targets for anti-angiogenic agents have been identified. The results of recent experimental studies have suggested that the frequent administration of certain chemotherapeutic agents at low doses, known as “metronomic chemotherapy”, may result in anti-angiogenic effects. The central importance of tumor neovascularization has been emphasized by clinical trials using anti-angiogenic therapy. The humanized monoclonal antibody against VEGF, bevacizumab, is the clinically most mature of the anti-angiogenic agents. Recently, a large phase III clinical trial demonstrated a significant benefit in progression-free survival with the addition of anti-VEGF monoclonal antibody bevacizumab to paclitaxel for the first-line treatment of advanced breast cancer. This study established that anti-angiogenic therapy is effective in breast cancer. Additional studies on bevacizumab, i.e. on its application in ovarian cancer, are underway. A variety of other anti-angiogenic agents are currently under clinical investigation and novel angiogenesis inhibitors are being developed. This article reviews the role of angiogenesis in the pathogenesis of cancer and the current treatment strategies for inhibiting tumor angiogenesis.

Schlüsselwörter

Tumor - Metastasierung - Anti‐Angiogenese - zielgerichtete Therapie

Key words

tumor - metastasis - anti‐angiogenesis - targeted therapy

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