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

David A. Reardon*, L. Burt Nabors, Roger Stupp, Tom Mikkelsen

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

175 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1225-1235
Number of pages11
JournalExpert Opinion on Investigational Drugs
Volume17
Issue number8
DOIs
StatePublished - Aug 2008

Funding

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. 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.

Keywords

  • Angiogenesis
  • Glioblastoma multiforme
  • Integrins
  • Malignant glioma
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

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