| First Author | Quail DF | Year | 2016 |
| Journal | Science | Volume | 352 |
| Issue | 6288 | Pages | aad3018 |
| PubMed ID | 27199435 | Mgi Jnum | J:231882 |
| Mgi Id | MGI:5775464 | Doi | 10.1126/science.aad3018 |
| Citation | Quail DF, et al. (2016) The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas. Science 352(6288):aad3018 |
| abstractText | 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. |
