mTOR inhibition by everolimus counteracts VEGF induction by sunitinib and improves anti-tumor activity against gastric cancer in vivo |
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Authors: | Thorsten Fuereder Agnes Jaeger-Lansky Doris Hoeflmayer Matthias Preusser Sabine Strommer Daniel Cejka Stefan Koehrer Richard Crevenna Volker Wacheck |
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Institution: | 1. Department of Clinical Pharmacology, Medical University Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria;2. Division of Oncology, Department of Internal Medicine I, Medical University Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria;3. Department of Physical Medicine and Rehabilitation, Medical University Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria |
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Abstract: | VEGF receptor blockage has been reported to increase serum VEGF. We hypothesized that mTOR inhibition by everolimus counteracts VEGF induction by sunitinib resulting in an improved anti-tumor activity of sunitinib. In vitro, sunitinib in combination with everolimus did not outperform the respective monotherapies. In vivo, monotherapies reduced tumor growth by 60%, whereas the combination of sunitinib and everolimus led to an almost complete tumor growth inhibition. This superior anti-tumor activity coincided with attenuation of VEGF peaks. In conclusion mTOR inhibition by everolimus counteracts VEGF induction by sunitinib and results in significant reduction of tumor burden and long-lasting tumor growth control. |
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Keywords: | Angiogenesis Gastric cancer mTOR Sunitinib VEGF |
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