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Targeting the Accomplices of MYC in MYC-driven Medulloblastoma

Institution: 
Sanford-Burnham Medical Research Institute
Researcher(s): 
Robert Wechsler-Reya, Ph.D.
Grant Type: 
Innovation Grants
Year Awarded: 
2014
Type of Childhood Cancer: 
Brain Tumors, Medulloblastoma
Project Description: 

Background
Medulloblastoma (MB) is the most common malignant brain tumor in children. Current treatments include surgery, radiation and high-dose chemotherapy. Although these treatments have allowed many patients to survive, approximately one-third of MB patients still die from the disease. Moreover, survivors suffer severe side effects from treatment, including dramatic losses in cognitive function, endocrine disorders and increased susceptibility to other cancers later in life.

New therapies are desperately needed, and are likely to come from understanding the molecules and pathways that control tumor growth.  MBs that have high levels of a protein called MYC are particularly aggressive, and are associated with the poorest prognosis. However, the mechanisms responsible for growth of these tumors remain poorly understood. We have recently identified a protein called GFI that cooperates with MYC to promote tumor formation. GFI functions by interacting with a set of proteins that are key regulators of gene expression.

Project Goal
We hypothesize that disrupting the interaction of GFI with these binding partners will inhibit growth of MYC-driven medulloblastoma. To test this hypothesis, we will determine if mutated forms of the GFI protein that cannot bind their partners are still able induce tumors. Moreover, we will test whether drugs that inhibit the activity of GFI binding partners can block the growth of MB cells. These studies will allow us to define the mechanisms driving this aggressive type of MB and develop novel treatment strategies to improve patient outcomes.

 

“I’m extremely grateful to ALSF for supporting our research. The studies we have proposed are risky, but if they are successful they will lead to improved outcomes for children with the most aggressive form of medulloblastoma, driven by the MYC oncogene.  Moreover, given the pivotal role of MYC in tumorigenesis, our findings may have implications for treatment of other pediatric cancers as well." 6/2014

2016 Update

Press Release La Jolla, Calif., March 14, 2016 -- Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified a new combination therapy for the most aggressive form of medulloblastoma, a fast growing type of pediatric brain cancer. The study was published online today in Cancer Cell, and is expected to lead to a clinical trial to confirm the benefits of the novel drug combination. For the full release use http://www.eurekalert.org/pub_releases/2016-03/spmd-ndc031116.php