Low-dose angiostatic tyrosine kinase inhibitors improve photodynamic therapy for cancer: lack of vascular normalization

Authors

  • Andrea Weiss,

    1. Medical Photonics Group, Institute of Bioengineering, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland
    2. Angiogenesis Laboratory, Department of Medical Oncology, VU Medical Center, Amsterdam, The Netherlands
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  • Judy R. van Beijnum,

    1. Angiogenesis Laboratory, Department of Medical Oncology, VU Medical Center, Amsterdam, The Netherlands
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  • Debora Bonvin,

    1. Medical Photonics Group, Institute of Bioengineering, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland
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  • Patrice Jichlinski,

    1. Department of Urology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
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  • Paul J. Dyson,

    1. Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland
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  • Arjan W. Griffioen,

    Corresponding author
    1. Angiogenesis Laboratory, Department of Medical Oncology, VU Medical Center, Amsterdam, The Netherlands
    • Correspondence to: Prof. Dr. Arjan W. GRIFFIOEN, Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.

      Tel.: +31-20-4443374

      Fax: +31-20-4443844

      E-mail: aw.griffioen@vumc.nl

      Dr. Patrycja NOWAK-SLIWINSKA, Department of Urology, Centre Hospitalier Universitaire Vaudois (CHUV),

      Rue du Bugnon 21, Lausanne CH-1011, Switzerland.

      Tel.: +41-21-3142981

      Fax: +41-21-3142982

      E-mail: Patrycja.Nowak-Sliwinska@chuv.ch

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  • Patrycja Nowak-Sliwinska

    Corresponding author
    1. Angiogenesis Laboratory, Department of Medical Oncology, VU Medical Center, Amsterdam, The Netherlands
    2. Department of Urology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
    • Correspondence to: Prof. Dr. Arjan W. GRIFFIOEN, Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.

      Tel.: +31-20-4443374

      Fax: +31-20-4443844

      E-mail: aw.griffioen@vumc.nl

      Dr. Patrycja NOWAK-SLIWINSKA, Department of Urology, Centre Hospitalier Universitaire Vaudois (CHUV),

      Rue du Bugnon 21, Lausanne CH-1011, Switzerland.

      Tel.: +41-21-3142981

      Fax: +41-21-3142982

      E-mail: Patrycja.Nowak-Sliwinska@chuv.ch

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Abstract

Photodynamic therapy (PDT) is an effective clinical treatment for a number of different cancers. PDT can induce hypoxia and inflammation, pro-angiogenic side effects, which may counteract its angio-occlusive mechanism. The combination of PDT with anti-angiogenic drugs offers a possibility for improved anti-tumour outcome. We used two tumour models to test the effects of the clinically approved angiostatic tyrosine kinase inhibitors sunitinib, sorafenib and axitinib in combination with PDT, and compared these results with the effects of bevacizumab, the anti-VEGF antibody, for the improvement of PDT. Best results were obtained from the combination of PDT and low-dose axitinib or sorafenib. Molecular analysis by PCR revealed that PDT in combination with axitinib suppressed VEGFR-2 expression in tumour vasculature. Treatment with bevacizumab, although effective as monotherapy, did not improve PDT outcome. In order to test for tumour vessel normalization effects, axitinib was also applied prior to PDT. The absence of improved PDT outcome in these experiments, as well as the lack of increased oxygenation in axitinib-treated tumours, suggests that vascular normalization did not occur. The current data imply that there is a future for certain anti-angiogenic agents to further improve the efficacy of photodynamic anti-cancer therapy.

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