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.