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Review
. 2008 Aug;17(8):1225-35.
doi: 10.1517/13543784.17.8.1225.

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

David A Reardon  1 , L Burt Nabors, Roger Stupp, Tom Mikkelsen
Affiliations
Review

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

David A Reardon et al. Expert Opin Investig Drugs. 2008 Aug.

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 alphavbeta3 and alphavbeta5 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.

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Conflict of interest statement

Declaration of interest: T Mikkelsen has received research funding from Merck KGaA. LB Nabors has served on the advisory board for Merck, has received honorarium and has contributed to the writing. R Stupp has acted as a consultant for Merck KGaA sponsored trials and has received honoraria.

Figures

Figure 1
Figure 1. Structure of cilengitide highlighting the RGD-binding domain (left) and the structure of integrin αv (red) and β3 (blue)
This demonstrates the binding of cilengitide through the RGD domain (right).
Figure 2
Figure 2. The perfusion MRI method of dynamic contrast susceptibility was used to determine tumor blood volume and flow and follow changes to these values during treatment with cilengitide
This example demonstrates a glioblastoma multiforme with enhancement on pre-treatment baseline noted on the T1 post gadolinium scan (upper panel) involving the medial and lateral left parietal lobe. The corresponding color map of the cerebral blood volume (bottom panel) reveals substantial signal (red) corresponding to areas of enhancement on the pre-treatment baseline consistent with robust angiogenesis. Of note is the fact that both the gadolinium enhancement and perfusion signals diminish sequentially following 8 and 16 weeks of cilengitide therapy, respectively.
Figure 3
Figure 3. Contrast-enhanced magnetic resonance images of representative responses to cilengitide
These include a patient who achieved a partial response (A) and a patient who achieved a complete response (B).
See this image and copyright information in PMC

References

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