A multi-institutional team led by Massachusetts General Hospital (MGH) researchers has identified a molecular pathway that appears to be essential for the growth and spread of medulloblastoma, the most common malignant brain tumor in children. In their report in the Feb. 28 issue of Cell, they show that blocking this pathway which involves interactions between tumor cells and the surrounding tissues leads to regression of all four molecular subtypes of medulloblastoma in several mouse models.
"Our finding that a pathway carrying signals from host cells to tumor cells via placental growth factor and its receptor neuropilin 1 is critical to the growth of medulloblastoma, regardless of molecular subtype, strongly supports evaluating antibodies against these proteins as a novel therapeutic approach to this pediatric cancer," says Rakesh K. Jain, PhD, director of the Steele Laboratory for Tumor Biology at MGH and corresponding author of the study.
A highly malignant tumor that originates in the cerebellum, medulloblastoma accounts for about 20 percent of all pediatric brain tumors and is ten times more common in children than in adults. While aggressive treatment with surgery, chemotherapy and radiation significantly improves patient survival, those treatments can have long-term developmental, behavioral, and neurological side effects, particularly in the youngest patients, making the need for less damaging therapies essential.
Impetus for the current investigation began with studies by Peter Carmeliet, MD, PhD, of the Vesalius Research Center in Belgium, a co-author of the current study. Carmeliet found that an antibody against placental growth factor (PlGF) could block angiogenesis in a number of adult tumors. Since PlGF, unlike other angiogenic proteins, is not required for normal postnatal development, Jain and his Steele Lab colleague Lei Xu, MD, PhD, proposed targeting PlGF as anti-angiogenic treatment for pediatric t
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Massachusetts General Hospital