Cilengitide in newly diagnosed glioblastoma: biomarker expression and outcome.

Détails

Ressource 1Télécharger: BIB_E7DED146FFB5.P001.pdf (8180.01 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_E7DED146FFB5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Cilengitide in newly diagnosed glioblastoma: biomarker expression and outcome.
Périodique
Oncotarget
Auteur(s)
Weller M., Nabors L.B., Gorlia T., Leske H., Rushing E., Bady P., Hicking C., Perry J., Hong Y.K., Roth P., Wick W., Goodman S.L., Hegi M.E., Picard M., Moch H., Straub J., Stupp R.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Statut éditorial
Publié
Date de publication
22/03/2016
Peer-reviewed
Oui
Volume
7
Numéro
12
Pages
15018-15032
Langue
anglais
Notes
Publication types: Clinical Trial, Phase II ; Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial
Publication Status: ppublish
Résumé
Integrins αvβ3 and αvβ5 regulate angiogenesis and invasiveness in cancer, potentially by modulating activation of the transforming growth factor (TGF)-β 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, αvβ3 and αvβ5 integrins, of αvβ8 and of their putative target, phosphorylation of SMAD2, in tumor tissues from CENTRIC (n=274) and CORE (n=224).αvβ3 and αvβ5 expression correlated well in tumor and endothelial cells, but showed little association with αvβ8 or pSMAD2 levels. In CENTRIC, there was no interaction between the biomarkers and treatment for prediction of outcome. In CORE, higher αvβ3 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 αvβ3, αvβ5 and αvβ8 are differentially expressed in glioblastoma. Integrin levels do not correlate with the activation level of the canonical TGF-β pathway. αvβ3 integrin expression may predict benefit from integrin inhibition in patients with glioblastoma lacking MGMT promoter methylation.

Mots-clé
Adult, Aged, Aged, 80 and over, Biomarkers, Tumor/metabolism, Cohort Studies, Female, Follow-Up Studies, Gene Expression Regulation, Neoplastic/drug effects, Glioblastoma/drug therapy, Glioblastoma/metabolism, Glioblastoma/pathology, Humans, Integrin alphaVbeta3/metabolism, Male, Middle Aged, Neoplasm Staging, Prognosis, Receptors, Vitronectin/metabolism, Smad2 Protein/metabolism, Snake Venoms/therapeutic use, Survival Rate, Young Adult, TGF-β, biomarker, glioblastoma, integrin, pSmad
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/02/2016 14:18
Dernière modification de la notice
20/08/2019 16:10
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