The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas

• DOI: 10.1126/science.aad3018
• Publication Date: 2016-05-20T05:57:49Z
• Authors: Daniela F. Quail; Robert L. Bowman; Leila Akkari; Marsha L. Quick; Alberto J. Schuhm...; Jason T. Huse; Eric C. Holland; James C. Sutton; Johanna A. Joyce
• Keywords: 0301 basic medicine; NFATC Transcription Factors; Macrophages; Imidazoles; Mice, Inbred Strains; Neoplasms, Experimental; Receptor, IGF Type 1; 3. Good health; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Drug Resistance, Neoplasm; Pyrazines; Antineoplastic Combined Chemotherapy Protocols; Human Umbilical Vein Endothelial Cells; Animals; Humans; Benzothiazoles; Insulin-Like Growth Factor I; Neoplasm Recurrence, Local; Glioblastoma; Picolinic Acids; Phosphoinositide-3 Kinase Inhibitors

Another pathway to cancer resistance

Therapies targeting the tumor microenvironment show promise for treating cancer. For example, antibodies targeting colony-stimulating factor-1 receptor (CSF-1R) inhibit protumorigenic macrophages and regress tumors in mouse models of glioblastoma multiforme (GBM), a deadly form of brain cancer. Quail et al. found that although CSR-1R blockade prolonged survival in mouse models of GBM, more than 50% of tumors eventually recurred. Recurrence was correlated with elevated PI3-K activity in tumors, driven by macrophage-secreted IGF-1. Blocking PI3-K and IGF-1 signaling in rebounding tumors prolonged survival. Thus, tumors can acquire resistance to therapy through intrinsic changes and through changes in their microenvironment.

Science , this issue p. 10.1126/science.aad3018