Developing a Novel Tumor Model to Screen for New Therapies for Spinal Ependymoma

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Linda M. Smith-Resar


CBTN Participants

CBTN Pre-clinical Models Used


Alex's Lemonade Stand Foundation

About this


Spinal ependymomas (SEs) are rare tumors of the central nervous system with limited treatment options and poor outcomes for more advanced disease. Successful treatment depends primarily upon complete surgical resection of the tumor, which is generally feasible only for well-differentiated (Grade I) myxopapillary tumors. In contrast, less differentiated tumors (Grades II-III) are often invasive, poorly circumscribed, and therefore difficult to resect. Unfortunately, SEs do not respond will to radiation therapy or chemotherapy and up to 50% will recur with poor outcomes following surgical resection. Recurrence is thought to result from persistent, stem-like, ependymoma-initiator cells. Even when SEs are resectable, children often suffer from significant sequelae, such as damage to the spinal cord from the tumor or surgery, in addition to radiation injury to nearby tissues. Impaired growth near the site of the tumor is also common, with resultant scoliosis, hypoplasia of paraspinal muscles, and even endocrinopathies. Because these tumors are rare, there are few tumor models and limited research to define underlying molecular lesions. To address this significant gap, we propose to develop an innovative tumor model based on the recent discovery that primary, ectodermally-derived tumor cells can be cultured indefinitely ex vivo on fibroblast feeder cells in the presence of a rho kinase inhibitor (ROCK inhibitor or Y-27632). These “conditionally reprogrammed cells (CRCs)” form spheres in vitro and replicate tumor pathology as xenografts in vivo.

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Ask the scientists

What are the goals of this project?

The goals of this project are to generate CRCs from primary tumors or normal developing spinal cord and to begin to screen a unique library of drugs (>3,000) already approved for use in humans for agents that selectively kill CRCs from tumor, but not normal tissue. This work will help to establish a unique tumor model and begin to identify new therapies for children with SE.

What is the impact of this project?

This work could provide a new paradigm for personalized therapy for children with spinal ependymomas, and possibly other tumors of ectodermal origins. If successful, we will translate our approach to the clinics to improve outcomes for children with high grade spinal ependymoma.

Specimen Data

The Children's Brain Tumor Network contributed to this project by providing cell lines.