Cilengitide: an integrin-targeting arginine–glycine–aspartic acid peptide with promising activity for glioblastoma multiforme

Abstract

Background: Glioblastoma multiforme (GBM), a highly invasive and vascular cancer, responds poorly to conventional cytotoxic therapy. Integrins, widely expressed in GBM and tumor vasculature, mediate cell survival, migration and angiogenesis. Cilengitide is a potent αvβ3 and αvβ5 integrin inhibitor. Objective: To summarize the preclinical and clinical experience with cilengitide for GBM. Methods: Preclinical studies and clinical trials evaluating cilengitide for GBM were reviewed. Results/conclusions: Cilengitide is active and synergizes with external beam radiotherapy in preclinical GBM models. In clinical trials for recurrent GBM, single-agent cilengitide has antitumor benefits and minimal toxicity. Among newly diagnosed GBM patients, single-arm studies incorporating cilengitide into standard external beam radiotherapy/temozolomide have shown encouraging activity with no increased toxicity and have led to a planned randomized Phase III trial.

Keywords::

• angiogenesis
• glioblastoma multiforme
• integrins
• malignant glioma
• vascular endothelial growth factor

Acknowledgements

This study was supported by National Institutes of Health grant nos. 1-P50-CA108786-01, NS20023, and CA11898 and by grant no. MO1 RR 30 through the General Clinical Research Centers Program, National Center for Research Resources, National Institutes of Health.