Effect of the Angiogenesis Inhibitor Cilengitide (Emd 121974) on Glioblastoma Growth in Nude Mice

Abstract

This standardized brain tumor model is highly reproducible and useful for testing new treatment regimens. Cilengitide is highly effective in suppressing blood vessel growth, thereby controlling orthotopic growth of this glioblastoma cell line.

Randomized Phase II Study of Cilengitide, an Integrin-Targeting Arginine-Glycine-Aspartic Acid Peptide, in Recurrent Glioblastoma Multiforme

“…[5][6][7] Cilengitide (EMD 121974; Merck KGaA, Darmstadt, Germany), a cyclic RGD peptide, competitively binds ␣v␤3 and ␣v␤5 integrin receptors. 8 Cilengitide 9,10 and other integrin inhibitors are active against preclinical GBM models, [11][12][13][14] and clinical studies also demonstrate encouraging antitumor benefit. In a recent phase I study, 10% of recurrent GBM patients achieved radiographic responses, and 31% achieved stable disease for a median of 5.4 months across a wide range of cilengitide dose levels.…”

Cilengitide: An RGD Pentapeptide ανβ3 and ανβ5 Integrin Inhibitor in Development for Glioblastoma and Other Malignancies

“…Preclinical studies demonstrate that cilengitide monotherapy has anti-tumor activity in xenograft tumor models and cilengitide can augment the activity of radiation and chemotherapy, including TMZ [36][37][38][39][40]. Cilengitide monotherapy and the combination of cilengitide with standard temozolomide (TMZ) and radiation have demonstrated consistent anti-tumor activity as well as a highly favorable safety profile across a spectrum of phase I and II clinical trials for both recurrent and newly diagnosed GBM patients [9,[41][42][43][44].…”

Acute Depletion of Endothelial β3-Integrin Transiently Inhibits Tumor Growth and Angiogenesis in Mice

“…The αvβ3-integrin antagonist studies, which show the potential to inhibit angiogenesis both in vitro 39 and in vivo 16,[40][41][42] when targeting the molecule, have always stood in seeming contrast to the enhanced angiogenesis observed in β3-integrinknockout mice. The findings we present here help to marry the conflicting results and, more importantly, to explain further the disappointing clinical outcomes achieved to date with αvβ3-integrin antagonism.…”