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Novel Strategy for Reducing Radiation-Induced Morbidity and Treating Recurrent Medulloblasoma

Massachusetts General Hospital
Rakesh Jain, PhD
Grant Type: 
Reach Grants
Year Awarded: 
Type of Childhood Cancer: 
General Pediatric Cancer
Project Description: 

Medulloblastoma is the most common malignant pediatric brain tumor. Current standard of the care of medulloblastoma is a combination of chemotherapy and radiation therapy. While this aggressive treatment regiment can potentially cure the disease, treatment-induced morbidities are devastating and furthermore, one third of patients relapse despite the treatment. Currently, there are no alternative therapies available for patients with recurrent tumors.

We have recently discovered that placental growth factor (PlGF) and its receptor Neuropilin-1 are highly expressed in medulloblastoma. Importantly, PlGF blockade significantly inhibited the medulloblastoma growth and metastatic spread of human medulloblastoma grown experimentally in mice as well as spontaneously arising medulloblastoma in genetically engineered animals (Snuderl et al, Cell,2013). We have also investigated the expression of PlGF and Neuropilin-1 in human medulloblastoma tissues and found the expression of these growth factor and receptor across different subtypes of medulloblastoma.

This is critical information for the translation to clinic as different subtypes of medulloblastoma often behave and respond to treatments differently. Based on these exciting findings, we will investigate the effects of anti-PlGF antibodies in combination with radiation in mouse models of medulloblastoma in two different clinical scenarios. First, we will test if PIGF blockade can improve curative treatment of primary tumor and hence, allows reducing radiation dose and side effects. Then, we will evaluate the effect of anti-PlGF therapy against the recurrent tumors after radiation. If successful, this novel treatment strategy for medulloblastoma can be rapidly translated in clinic as we have done so for other tumors.