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Mechanisms of PPM1D in Medulloblastoma Tumorigenesis and Invasion

Emory University
Robert Craig Castellino, MD
Grant Type: 
Bridge Grants
Year Awarded: 
Type of Childhood Cancer: 
Brain Tumors, Medulloblastoma
Project Description: 

Brain tumors are the most common solid cancers in children. Medulloblastoma is the most common aggressive childhood brain tumor and has many treatment-related effects including stunted growth, impaired ability to think and learn, and damage to other normal brain functions. Tumor spread to distant sites within and outside the brain is associated with poor survival. In addition, if medulloblastoma re-appears after treatment, there are no therapies currently available that can help. The cancer-causing gene WIP1 is expressed at high levels in over 50% of medulloblastomas. A high level of WIP1 is associated with medulloblastoma tumor spread all over the brain and down the spinal column, and reduces the chance that a patient will survive. The research proposed in this application will determine how WIP1-expressing medulloblastomas spread and why they are more difficult to treat. We will identify the important molecules that cause aggressive growth and test new therapeutic strategies for preventing growth and spread of WIP1-expressing medulloblastomas. Successful completion of this project will improve our understanding of how medulloblastomas become aggressive. Our long-term contribution will be the development of novel, highly effective strategies for treatment of aggressive medulloblastomas. Ultimately, our research will lead to significant improvements in both the survival and quality of life of children diagnosed with medulloblastoma.