With the TAMs blockaded by CSF-1 inhibitors, it was the tumor cells that showed increased rates of apoptosis. The TAMs were not even depleted in the treated mice, despite the drug blockade of their growth factor. Instead the TAMs survived by responding to growth factors secreted by the gliomas, including GM-CSF and IFN-γ, according to Dr. Joyce.
The MSKCC researchers also found that tumor spheres, freshly isolated from glioma patients in the surgery department at MSKCC, responded to the drug when implanted in animals. The CSF-1R blockade slowed intracranial growth in the patient-derived glioma xenografts.
Because GBM is the most common glioma, its genome was the first to be sequenced for the Cancer Genome Atlas, which parsed GBM into four genetic subtypes: proneural, neural, classical and mesenchymal. The mice used in Dr. Joyce's lab experiments model the proneural GBM subtype. All forms of GBM have a 2- to 3-person per 100,000 incidence rate in the U.S. and Europe, according to the National Brain Tumor Society. Because of its highly invasive phenotype, GBM is almost impossible to resect completely in surgery. Drug and radiation treatments are the standard follow-ups.
Dr. Joyce says that these new results, which were first reported only two months ago in Nature Medicine, http://www.ncbi.nlm.nih.gov/pubmed/24056773, are encouraging for planned clinical trials of CSF-1R inhibitors in combination with radiation therapy in glioma patients.
"We are optimistic that CSF-1R inhibitors may provide a more effective therapy than current treatments for the disease management of glioma patients," Dr. Joyce said.
|Contact: Cathy Yarbrough