Cilengitide in newly diagnosed glioblastoma: biomarker expression and outcome.

ABSTRACT: Integrins ?v?3 and ?v?5 regulate angiogenesis and invasiveness in cancer, potentially by modulating activation of the transforming growth factor (TGF)-? pathway. The randomized phase III CENTRIC and phase II CORE trials explored the integrin inhibitor cilengitide in patients with newly diagnosed glioblastoma with versus without O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. These trials failed to meet their primary endpoints.Immunohistochemistry was used to assess the levels of the target integrins of cilengitide, ?v?3 and ?v?5 integrins, of ?v?8 and of their putative target, phosphorylation of SMAD2, in tumor tissues from CENTRIC (n=274) and CORE (n=224).?v?3 and ?v?5 expression correlated well in tumor and endothelial cells, but showed little association with ?v?8 or pSMAD2 levels. In CENTRIC, there was no interaction between the biomarkers and treatment for prediction of outcome. In CORE, higher ?v?3 levels in tumor cells were associated with improved progression-free survival by central review and with improved overall survival in patients treated with cilengitide.Integrins ?v?3, ?v?5 and ?v?8 are differentially expressed in glioblastoma. Integrin levels do not correlate with the activation level of the canonical TGF-? pathway. ?v?3 integrin expression may predict benefit from integrin inhibition in patients with glioblastoma lacking MGMT promoter methylation.

SUBMITTER: Weller M 

PROVIDER: S-EPMC4924768 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature