IronMatt Grant Recipient Finds Promising Medulloblastoma Therapy Target

medulloblastoma study

Current treatments have improved the survival rate of children with medulloblastoma, but children who fall under the high-risk category are prone to having the tumor spread to other parts of the brain and spine. 

The challenge for doctors is that the mechanism of the cancer’s growth and dissemination are poorly understood. To help, a 2015 IronMatt grant recipient, Samuel H. Cheshire, conducted a study exploring Anti NRR1 as a novel therapeutic against human c-Myc Driven Medulloblastoma. The study was published in Nature Communications in 2018.

Here’s how Dr. Cheshire described the study in his grant application:

“Metastasis in such cases is seen in very high numbers, often requiring more aggressive therapies at the cost of significant life-long mental and physical impairments. In fact most medulloblastoma patients die from inoperable metastasis rather than the primary tumor.

“Despite this obvious need, very little research has focused on medulloblastoma metastasis. Notch1 is a cell membrane receptor known to play a multi-faceted role in the signaling of cancer cells. We present an animal model of patient-derived medulloblastoma cells that shows the spread of the tumor to the spine, recapitulating the natural progression of medulloblastoma and, therefore, allows us to identify the molecular pathways that play a crucial role in medulloblastoma metastasis.

“Preliminary studies in our lab have shown increased expression and activity of Notch1 in Medulloblastoma spinal metastasis. We intend to further investigate the effects of blocking Notch1 signaling in prevention of medulloblastoma growth and metastasis through the use of a highly specific and potent blocker of Notch1. Data gathered from these preclinical studies will address our hypothesis that this blocking agent is a safe and effective treatment for medulloblastoma patients, and will be able to replace standard of care treatments in the foreseeable future.”

Data gathered from the study indicates that Group 3 medulloblastoma cells that metastasize to the spinal cord arise from a distinct subpopulation of tumor cells with increased NOTCH1 pathway activity and expression.

The findings suggest that “NOTCH1-induced medulloblastoma metastasis occurs through TWIST1-induced BMI1 activation. In conjunction with the low adverse effects of specifically inhibiting NOTCH1,116, this pathway represents a promising target for therapy of Group 3 medulloblastoma.”

Help Us Find a Cure for This Deadly Disease

Currently, research into childhood brain cancers are severely underfunded. It’s through foundations like IronMatt that many of these trials are able to be run.

Let’s continue finding better treatments. Please donate to this important cause. Every dollar makes a difference.