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Targeting integrins in malignant glioma

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Abstract

The integrin family of cell adhesion receptors is emerging as a promising target of anticancer therapy. AlphaVbeta3 and alphaVbeta5 integrins are overexpressed on both glioma cells and tumor vasculature. Cilengitide, the most advanced specific integrin inhibitor in oncology, has shown antitumor activity against glioma in early clinical trials. Durable remissions have been observed in phase I and phase II trials for recurrent glioblastoma (GBM) with both lower and higher doses of cilengitide. Pilot trials in newly diagnosed glioblastoma in conjunction with standard chemoradiotherapy have been encouraging. Preclinical data suggest synergy with concomitant chemo- and radiation therapy. A pivotal phase III study (CENTRIC) in newly diagnosed GBM patients is currently recruiting. This paper summarizes the current understanding of the role of integrins and their inhibition in gliomagenesis. The background and design of ongoing trials are outlined.

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Conflict of interest statement

The authors have no significant conflict of interest to declare. The paper was written by G. Tabatabai and R. Stupp, with review, input, comments and final approval by all authors. The authors have conducted and are conducting industry and/or NCI-sponsored trials with cilengitide.

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Authors and Affiliations

  1. Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland

    Ghazaleh Tabatabai & Michael Weller

  2. Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA

    Burt Nabors

  3. Global Clinical Development Unit Oncology, Merck KGaA, Frankfurter Strasse 250, 64293, Darmstadt, Germany

    Martin Picard

  4. Departments of Surgery and Pediatrics, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA

    David Reardon

  5. Department of Neurosurgery, Hermelin Brain Tumor Center, Henry Ford Hospital, Detroit, MI, USA

    Tom Mikkelsen

  6. Department of Neurology, Hermelin Brain Tumor Center, Henry Ford Hospital, Detroit, MI, USA

    Tom Mikkelsen

  7. Division of Experimental Oncology, Centre Pluridisciplinaire d’Oncologie, Faculty of Biology and Medicine, University of Lausanne, and NCCR Molecular Oncology ISREC-EPFL, Epalinges, Switzerland

    Curzio Ruegg

  8. Pathology, Med3, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland

    Curzio Ruegg

  9. Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland

    Roger Stupp

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  1. Ghazaleh Tabatabai
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  2. Michael Weller
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  3. Burt Nabors
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  5. David Reardon
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  6. Tom Mikkelsen
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  7. Curzio Ruegg
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Correspondence to Ghazaleh Tabatabai or Roger Stupp.

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Tabatabai, G., Weller, M., Nabors, B. et al. Targeting integrins in malignant glioma. Targ Oncol 5, 175–181 (2010). https://doi.org/10.1007/s11523-010-0156-3

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