Cilengitide in newly diagnosed glioblastoma: biomarker expression and outcome.

摘要: // Michael Weller 1 , Louis Burt Nabors 2 Thierry Gorlia 3 Henning Leske 4 Elisabeth Rushing Pierre Bady 5, 6, 7 Christine Hicking 8 James Perry 9 Yong-Kil Hong 10 Patrick Roth Wolfgang Wick 11, 12 Simon L. Goodman Monika E. Hegi Martin Picard Holger Moch 13 Josef Straub Roger Stupp 14 Department of Neurology, University Hospital Zurich and Zurich, Switzerland Alabama at Birmingham, AL, USA EORTC Data Centre, Brussels, Belgium Institute Neuropathology, 5 Education Research, Lausanne, 6 SIB Swiss Bioinformatics, Clinical Neurosciences, Translational Biomarkers Oncology, Merck KGaA, Darmstadt, Germany Sunnybrook Health Sciences Toronto, ON, Canada The Catholic Korea, Seoul St. Mary’s Hospital, Seoul, Korea 11 Neurology Clinic, Heidelberg, Cooperation Unit (CCU) Neurooncology, German Cancer Consortium (DKTK), Research Center (DKFZ), Surgical Pathology, Correspondence to: Weller, e-mail: michael.weller@usz.ch Keywords: glioblastoma, integrin, pSmad, TGF-β, biomarker Received: January 03, 2016     Accepted: 29, Published: February 22, 2016 ABSTRACT Integrins αvβ3 αvβ5 regulate angiogenesis invasiveness in cancer, potentially by modulating activation the transforming growth factor (TGF)-β pathway. randomized phase III CENTRIC II CORE trials explored integrin inhibitor cilengitide patients with newly diagnosed glioblastoma versus without O -methylguanine DNA methyltransferase ( MGMT ) promoter methylation. These failed to meet their primary endpoints. Immunohistochemistry was used assess levels target integrins cilengitide, integrins, αvβ8 putative target, phosphorylation SMAD2, tumor tissues from (n=274) (n=224). expression correlated well endothelial cells, but showed little association or pSMAD2 levels. In CENTRIC, there no interaction between biomarkers treatment for prediction outcome. CORE, higher cells were associated improved progression-free survival central review overall treated cilengitide. αvβ3, are differentially expressed glioblastoma. Integrin do not correlate level canonical TGF-β may predict benefit inhibition lacking