Ependymoma is one of the most common malignant brain tumors in children and adolescents. It develops in the ependymal tissue, which lines the brain’s ventricles and the central canal of the spinal cord. These tumors can be found in various locations, including different brain ventricles (most commonly) or along the central canal of the spinal cord. Intracranial ependymomas in children are the most common and have a poor prognosis, with a 5-year mortality rate of up to 40%. The standard treatment involves surgery followed by or without radiotherapy, with chemotherapy being a rare option. However, many patients experience serious treatment-related sequelae throughout their lives.
Improving the therapeutic management of children with this cancer remains a challenge, both at the time of diagnosis and in the long term, to prevent the development of chronic conditions. To achieve this goal, it is crucial to develop innovative models that represent the characteristics of these cancers, to understand their molecular bases, and to envision new targeted therapeutic strategies adapted to the specificities of a developing organism.
About the Project
Dr. Leblond and his team have developed 3D tumor avatars, called tumoroids, of ependymomas that recapitulate all the characteristics of the tumors from which they originate. After characterizing each designed tumoroid, especially through genome sequencing, these tools have been used in drug screening to identify new drug candidates and define potential resistance mechanisms. These efforts contribute to the development of innovative models that can be used by the entire scientific community to establish the etiology of these cancers. Additionally, these models are beneficial for conducting pharmaceutical screenings of small molecules as part of personalized medicine approaches.
Study Objectives
- Designing tumoroids in culture from patient samples with ependymomas: optimizing culture conditions and establishing a pediatric ependymoma tumoroid biobank.
- Characterizing the obtained tumoroids (before establishing the biobank) compared to their original tissue to validate their relevance.
- Developing a molecule screening (apoptosis modulators) on the model to identify molecules capable of inducing cell death and thus overcoming treatment resistance.
Project Progress
- 11 biopsies from 11 patients have been cultured and analyzed.
- Transcriptomic analysis has been performed on a cohort of 65 ependymomas (GSE50385) to identify the main signaling pathways involved in the proliferation and survival of ependymoma cells. By comparing these transcriptomic analyses with those of the obtained tumoroids, it has been confirmed that this model is molecularly similar to its original tumor tissue.
- Thanks to this funding, further funding (from Canceropôle CLARA) allows continuation of this project: multi-omic characterization of models and screening of potentially active molecules against ependymomas.
Project Summary
- Promoter: Centre Léon Berard de Lyon
- Principal Investigator: Dr. Pierre Leblond
- Program Duration: December 2020 – December 2022
- Countries Involved: France
- Imagine for Margo Funding: €37,200 (project selected by SFCE)
