Thrombininduziertes Tumorwachstum

Zusammenfassung

Das zentrale Gerinnungsenzym, die Serinproteinase Thrombin, kann über die Protease-aktivierten Rezeptoren 1 und 4 der Tumorzellen in deren Wachstum modulierend eingreifen. Das Thrombin ist im Tumormikroenvironment permanent verfügbar, Meizothrombin wird an einem tumorspezifischen Aktivierungskomplex aus Prothrombin generiert und kann ebenfalls das Tumorzellwachstum via PAR-1 und dem 7-Transdomänen-Protein-Rezeptor-Signalweg beeinflussen. PEG-gekoppelte direkte Thrombininhibitoren, die eine spezielle pharmakokinetische Charakteristik aufweisen und für eine langzeitige Wirksamkeit im extrazellulären Wasserraum designt wurden, kontrollieren die Serinproteinaseaktivität im Tumormikroenvironment und haben damit eine hohe potenzielle tumortherapeutische Wirksamkeit. In xenografischen Tumormodellen hat diese neue Substanzklasse einen signifikanten kanzerostatischen Effekt gezeigt.

Summary

The central enzyme of blood coagulation, the serine proteinase thrombin, is capable to modify the growth of tumour cells by interaction with protease activated receptors 1 and 4 of the tumour cells. Thrombin is permanently available in tumour micro environment; meizothrombin is generated from prothrombin at a tumour specific activation complex and can influence tumour cell growth via PAR-1 and 7-transdomain protein receptor signalling pathway, too. PEG-coupled direct thrombin inhibitors that possess special pharmacokinetic characteristics and that have been designed for long lasting efficacy in extracellular space, control serine proteinase activity in tumour micro environment and therefore they own a high potential anti-tumour efficacy. In xenographic tumour models this new substance class has shown a significant carcinostatic effect.

Schlüsselwörter

Thrombin - Meizothrombin - Tumormikroenvironment - PAR-1 - PEG-gekoppelte direkte Thrombininhibitoren

Keywords

Thrombin - meizothrombin - tumour micro environment - PAR-1 - PEG-coupled direct thrombin inhibitors

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