The development of novel therapiesfor bevacizumab-induced brain tumor invasion

2016 Fiscal Year Final Research Report

• Project/Area Number: 26670644
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Okayama University
• Principal Investigator: Date Isao 岡山大学, 医歯薬学総合研究科, 教授 (70236785)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: Bevacizumab / Integrin / Molecular targeted drug / invasion / glioma

Outline of Final Research Achievements

Glioblastoma is known to secrete high levels of vascular endothelial growth factor (VEGF). Clinical studies with bevacizumab, a monoclonal antibody to VEGF, have demonstrated convincing therapeutic benefits in glioblastoma patients. However, its induction of invasive proliferation has also been reported. We examined the effects of treatment with cilengitide, an integrin inhibitor, on bevacizumab-induced invasive changes in glioma. U87ΔEGFR cells were stereotactically injected into the brain of nude mice or rats. When the rats were treated with a combination of bevacizumab and cilengitide, the depth of tumor invasion was significantly less than with only bevacizumab. Pathway analysis demonstrated the inhibition of invasion associated genes such as the integrin-mediated cell adhesion pathway in the combination group. This study showed that the combination of bevacizumab with cilengitide exerted its anti-invasive effect.

Free Research Field

医歯薬学、外科系臨床医学、脳神経外科学