Neue Strategien beim NSCLC: Was bringt die Hemmung der Tumorgefäße?

Zusammenfassung

Lungenkarzinome sind die am häufigsten zum Tode führenden Tumorerkrankungen in Deutschland. Das verbesserte Verständnis der Tumorbiologie und der Bedeutung eines funktionellen Gefäßsystems für das Wachstum und die Metastasierung solider Tumoren resultierte in der Entwicklung neuer Substanzen, die vorwiegend das Gefäßsystem des Tumors zerstören sollen. Anti-angiogene Substanzen hemmen die Neuentstehung von Gefäßen aus dem bereits existierenden Gefäßsystem und können die Gefäßstabilität beeinflussen. Mit Bevacizumab wurde bereits ein monoklonaler anti-VEGF-(vascular endothelial growth factor)-Antikörper zur Erstlinien-Behandlung des metastasierten oder fortgeschrittenen nicht kleinzelligen Lungenkarzinoms (NSCLC) ohne dominierende Plattenepithelhistologie in Kombination mit Platin-basierter Chemotherapie zugelassen. Klinische Studien zeigten vielversprechende Daten auch für die Kombination von klein-molekularen multi-Tyrosinkinase-Inhibitoren mit Zytostatika. Als differenter Therapieansatz wurden gefäßzerstörende Substanzen (Vascular Disrupting Agents, VDAs) entwickelt, die insbesondere etablierte Blutgefäße im Tumor zerstören sollen. In der vorliegenden Übersicht werden die Wirkprinzipien von anti-angiogenen Therapeutika und VDAs beschrieben und die aktuelle klinische Datenlage zusammengefasst.

Abstract

Lung cancer is the leading cause of cancer-related mortality in Germany. Improvements in our understanding of cancer biology have led to the development of novel agents that inhibit the tumour vasculature in order to induce subsequent tumour cell death. In this context, the inhibition of tumour-related angiogenesis - the growth of new vessels from pre-existing vessels – has become an attractive target for anticancer therapy. Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has already been approved in combination with platinum-based chemotherapy in patients with advanced non–small cell lung cancer (NSCLC) without predominant squamous cell histology. Moreover, small molecule inhibitors targeting multiple angiogenic receptors have also shown promise when combined with standard chemotherapy. As a different approach, vascular disrupting agents (VDAs) have been designed to particularly target preexisting blood vessels which may lead to a vascular shut-down. In the present review, both principles of action and current clinical data on anti-angiogenic agents and VDAs in the treatment of patients with NSCLC are reviewed.

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