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Translation molekularer Zusammenhänge in die klinische Anwendung

Dargestellt am Beispiel des Vascular-Endothelial-Growth-Factor- (VEGF-)Pathway

Translational research in renal cell cancer

Illustrated by the example of the vascular endothelial growth factor pathway

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Der Urologe Aims and scope Submit manuscript

Zusammenfassung

Für Patienten mit metastasiertem Nierenzellkarzinom sind die therapeutischen Möglichkeiten nach Versagen der Zytokintherapie sehr limitiert. Es besteht ein großer Bedarf an neuen Substanzen, die in dieser Therapiesituation wirksam sind. Wegen der konsekutiven Hochregulierung nach Funktionsverlust des Von-Hippel-Lindau-Gens ist die Signalkaskade des Vascular Endothelial Growth Factor (VEGF) ein vielversprechender Ansatzpunkt für eine molekular-zielgerichtete Therapie. In den vergangenen Jahren wurden Therapeutika entwickelt, die an verschiedenen Punkten dieser Signalkaskade eingreifen. Die vorliegende Arbeit skizziert die zugrunde liegenden molekularen Mechanismen und gibt einen Überblick über die Substanzen, die derzeit in klinischen Studien beim metastasierten Nierenzellkarzinom eingesetzt werden. Bisherige klinische Erfolge sind vielversprechend, auch wenn die besten Therapiezeitpunkte, Dosierungen, mögliche Kombinationsregime und die Dauer des Ansprechens in der Zukunft definiert und erfasst werden müssen.

Abstract

For patients with metastatic renal cell cancer (RCC), therapeutic options after cytokine failure are rather limited. There is a considerable need to identify new substances for systemic therapy. Due to upregulation after the loss of a functional von Hippel Lindau gene product, the vascular endothelial growth factor (VEGF) pathway is a promising target for a molecular based therapy. Over the last few years, therapeutic agents have been developed which inhibit this pathway at various levels. Here, we provide an overview of the molecular background and currently used drugs which have entered clinical trials in the setting of metastatic RCC disease. Until now, the results from early clinical trials are very promising, however, the best schedule, dosage, potential combination regimens, as well as long time efficacy, are still to be determined.

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Interessenkonflikt:

Der korrespondierende Autor weist auf eine Verbindung mit folgender Firma/Firmen hin: M.A., K.H., P.B., J.G. und M.R. waren als Investigator oder Principal Investigator an klinischen Studien mit BAY 43–9006 oder SU11248 beteiligt.

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Authors and Affiliations

  1. Urologische Universitätsklinik und Poliklinik, Universität Ulm

    R. Kuefer, M. Autenrieth, K. Herkommer, M. Hofer, L. Rinnab & J. Gschwend

  2. Urologische Abteilung, Eberhard-Karls-Universität, Tübingen

    A. Merseburger

  3. Department of Pathology, Brigham and Women’s Hospital, Boston, USA

    M. Hofer

  4. Abteilung für Innere Medizin III, Universitätsklinikum Ulm

    P. Blum &  M. Ringhoffer

  5. Abteilung für Innere Medizin III, Universitätsklinikum Ulm, Robert-Koch-Straße 8, 89081, Ulm

    M. Ringhoffer

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  1. R. Kuefer
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Correspondence to M. Ringhoffer.

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Kuefer, R., Autenrieth, M., Herkommer, K. et al. Translation molekularer Zusammenhänge in die klinische Anwendung . Urologe 45, 328–335 (2006). https://doi.org/10.1007/s00120-006-1006-x

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  • DOI: https://doi.org/10.1007/s00120-006-1006-x

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