Glioblastoma multiforme (GBM), a highly aggressive brain tumor, has a poor prognosis as patients affected from this disease poorly respond to chemotherapy, radiotherapy, and surgery.
Stephanie Pyonteck, Memorial Sloan-Kettering Cancer Center, New York, USA, and colleagues described a new drug that prevents GBM development by targeting immune cells known as macrophages. Although these cells normally protect the organism from infections, during cancer development they accumulate in the tumor microenvironment and stimulate cancerous growth. The researchers targeted these tumor-associated macrophages by using BLZ945 (pictured), a drug that selectively and potently inhibits the CSF-1 receptor, a protein present almost exclusively on the macrophages’ surface.
Although BLZ945 did not cause the death of tumor-associated macrophages, it mitigated their cancer-promoting role and, at the same time, it re-educated these cells to react against the tumor by engulfing and eliminating glioblastoma cells.
BLZ945 may thus open important therapeutic avenues in the treatment of GBM.
- CSF-1R inhibition alters macrophage polarization and blocks glioma progression,
Stephanie M. Pyonteck, Leila Akkari, Alberto J. Schuhmacher, Robert L. Bowman, Lisa Sevenich, Daniela F. Quail, Oakley C Olson, Marsha L. Quick, Jason T. Huse, Virginia Teijeiro, Manu Setty, Christina S. Leslie, Yoko Oei, Alicia Pedraza, Jianan Zhang, Cameron W. Brennan, James C. Sutton, Eric C. Holland, Dylan Daniel, Johanna A. Joyce,
Nat. Med. 2013, 19, 1264–1272.