The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas.
Détails
ID Serval
serval:BIB_F2EFF73DAC5C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas.
Périodique
Science
ISSN
1095-9203 (Electronic)
ISSN-L
0036-8075
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
352
Numéro
6288
Pages
aad3018
Langue
anglais
Résumé
Macrophages accumulate with glioblastoma multiforme (GBM) progression and can be targeted via inhibition of colony-stimulating factor-1 receptor (CSF-1R) to regress high-grade tumors in animal models of this cancer. However, whether and how resistance emerges in response to sustained CSF-1R blockade is unknown. We show that although overall survival is significantly prolonged, tumors recur in >50% of mice. Gliomas reestablish sensitivity to CSF-1R inhibition upon transplantation, indicating that resistance is tumor microenvironment-driven. Phosphatidylinositol 3-kinase (PI3K) pathway activity was elevated in recurrent GBM, driven by macrophage-derived insulin-like growth factor-1 (IGF-1) and tumor cell IGF-1 receptor (IGF-1R). Combining IGF-1R or PI3K blockade with CSF-1R inhibition in recurrent tumors significantly prolonged overall survival. Our findings thus reveal a potential therapeutic approach for treating resistance to CSF-1R inhibitors.
Pubmed
Web of science
Création de la notice
06/06/2016 17:25
Dernière modification de la notice
20/08/2019 17:20