Targeting integrins in malignant glioma.
The integrin family of cell adhesion receptors is emerging as a promising target of anticancer therapy. AlphaVbeta3 and alphaVbeta5 integrins are overexpressed on both glioma cells and tumor vasculature. Cilengitide, the most advanced specific integrin inhibitor in oncology, has shown antitumor activity against glioma in early clinical trials. Durable remissions have been observed in phase I and phase II trials for recurrent glioblastoma (GBM) with both lower and higher doses of cilengitide. Pilot trials in newly diagnosed glioblastoma in conjunction with standard chemoradiotherapy have been encouraging. Preclinical data suggest synergy with concomitant chemo- and radiation therapy. A pivotal phase III study (CENTRIC) in newly diagnosed GBM patients is currently recruiting. This paper summarizes the current understanding of the role of integrins and their inhibition in gliomagenesis. The background and design of ongoing trials are outlined.
Tabatabai
Ghazaleh
G
Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland. ghazaleh.tabatabai@usz.ch
Weller
Michael
M
Nabors
Burt
B
Picard
Martin
M
Reardon
David
D
Mikkelsen
Tom
T
Ruegg
Curzio
C
Stupp
Roger
R
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
D000970:Antineoplastic Agents; D016023:Integrins
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