The role of integrins in glioma biology and anti-glioma therapies

Ghazaleh Tabatabai*, Jörg Christian Tonn, Roger Stupp, Michael Weller

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

37 Scopus citations


The tumor environment is critical for tumor maintenance and progression. Integrins are a large family of cell surface receptors mediating the interaction of tumor cells with their microenvironment and play important roles in glioma biology, including migration, invasion, angiogenesis and tumor stem cell anchorage. Here, we review preclinical and clinical data on integrin inhibition in malignant gliomas. Various pharmacological approaches to the modulation of integrin signaling have been explored including antibodies and peptide- based agents. Cilengitide, a cyclic RGD-mimetic peptide of αvβ3 and αvβ5 integrins is in advanced clinical development in glioblastoma. Cilengitide had only limited activity as a single agent in glioblastoma, but, when added to standard radiochemotherapy, appeared to prolong progression-free and overall survival in patients with newly diagnosed glioblastomas and methylation of the promoter of the O6 methylguanine methyltransferase (MGMT) gene. MGMT gene promoter methylation in turn predicts benefit from alkylating chemotherapy. A phase III randomized clinical trial in conjunction with standard radiochemotherapy in newly diagnosed glioblastoma patients with MGMT gene promoter methylation has recently completed accrual (EORTC 26071-22072). A companion trial explores a dose-escalated regimen of cilengitide added to radiotherapy plus temozolomide in patients without MGMT gene promoter methylation. Promising results in these trials would probably result in a broader interest in integrins as targets for glioma therapy and hopefully the development of a broader panel of anti-integrin agents.

Original languageEnglish (US)
Pages (from-to)2402-2410
Number of pages9
JournalCurrent Pharmaceutical Design
Issue number23
StatePublished - Aug 2011


  • Angiogenesis
  • Clinical trials
  • Glioma
  • Integrins

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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