Developing a Novel Tumor Model to Screen for New Therapies for Spinal Ependymoma
We propose to develop an innovative assay to identify new, personalized therapy for children with aggressive spinal ependymomas (SE). SEs are rare tumors with limited treatment options for more advanced disease. Successful treatments rely on surgical removal and local radiation therapy to the spine, although these approaches are often associated with significant side effects, including scoliosis (abnormal spine curvature), decreased growth of nearby muscles, and tissue damage from radiation exposure. Unfortunately, up to 50% will recur with poor outcomes. Because SEs are rare, there are no established tumor models nor are there many studies to identify the underlying causes or better therapies. To fill this knowledge gap, we propose to establish a novel experimental model by growing tumor cells under specialized conditions used for normal stem cells. Specifically, tumor cells will be isolated and placed on top of mouse "feeder" cells with a chemical (Rho kinase inhibitor). These conditions "reprogram" cells such that they become "immortalized" or capable of surviving and dividing indefinitely.
The "conditionally reprogrammed cells (CRCs)" were recently used to discover an effective therapy for a pediatric patient with an unusual lung tumor (respiratory papillomatosis).
Based on these exciting discoveries, we now propose to: 1) Derive CRCs from children with SE, and, 2) Screen a library of clinically-approved drugs to identify agents that preferentially kill tumor cells, but not cells from normal spinal tissue. This novel approach could provide a new paradigm for identifying effective, personalized therapy for children with spinal cord ependymomas.