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Blocking tumor-associated macrophages decreased glioblastoma's growth & extended survival in mice
Date:12/15/2013

An experimental drug that targets macrophages, a type of immune cells, in the microenvironment surrounding the lethal brain tumor glioblastoma multiforme decreased the cancer's growth and extended survival of laboratory mice with the cancer, scientists will report on Tuesday Dec. 17, at the American Society for Cell Biology (ASCB) annual meeting in New Orleans.

The rates of apoptosis, or programmed cell death, were higher in the mice treated with the experimental agent than in the untreated animals that also had high-grade glioblastomas, said Johanna Joyce, Ph.D., of the Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City. As a result, the drug-treated laboratory mice survived many months longer than the untreated animals with the same cancer.

The experimental drug blocks cell receptors for colony-stimulating factor-1 (CSF-1R), which is essential to the differentiation and survival of tumor-associated macrophages and microglia (TAMS), which are the brain's front-line immune defense cells. The microenvironment that surrounds brain tumors contains many macrophages with this receptor.

Glioblastoma multiforme (GBM) is the most common and the most deadly adult primary brain tumor, with an average survival of just 14 months following diagnosis. Even with aggressive treatment by surgery, radiation and chemotherapy, most therapeutic approaches targeting the glioma cells in GBM fail.

Faced with this bleak picture, Dr. Joyce and colleagues MSKCC looked for an alternative strategy and turned to the cancer's cellular neighbors, the non-tumor cells that are part of the glioma microenvironment. In particular, they zeroed in on tumor-associated macrophages and TAMs.

When Dr. Joyce's lab used an inhibitor of the CSF-1 receptor (CSF-1R) to target TAMs in a mouse model of GBM, the treated mice survived many months longer than the control cohort. Their established, high-grade gliomas regressed in proliferation and maligna
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Contact: Cathy Yarbrough
cyarbrough@ascb.org
858-243-1814

John Fleischman
jfleischman@ascb.org

American Society for Cell Biology
Source:Eurekalert


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