“Encourager” is a project to explore the cellular origins of therapeutic failure in pediatric gliomas, in order to optimize targeted therapies.
Children’s Brain Cancers
Brain tumors are the most common solid tumors in children. The annual number of new cases for all children’s brain tumors is estimated at approximately 30 per million.
Gliomas encompass tumors of the central nervous system, varying by the originating brain cells (astrocytes, oligodendrocytes, or both) and their aggressiveness (ranging from less to more aggressive: low-grade glioma, anaplastic glioma, and high-grade gliomas).
Gliomas are the most common brain tumors in children and adolescents. Low-grade (benign) gliomas are more frequent in younger children, while malignant gliomas affect older children and adolescents. These tumors include well-prognosed forms like pilocytic astrocytoma and more challenging types like diffuse intrinsic pontine glioma.
About ENCOURAGER
Despite recent advancements in detection and therapies, brain tumors remain the leading cause of cancer-related deaths among children in Europe. Approximately 1 in 4 children or adolescents with a brain tumor dies due to tumor recurrence and treatment failure. The ability to detect molecular changes in tumors has led to improved therapies that disrupt cancer-specific mutations. These targeted therapies are increasingly used in clinics, often as personalized treatments for high-risk children who have exhausted standard therapeutic options. Significant responses to targeted therapies are observed in some, but not all, patients. Even when patients respond, sustained tumor control is rarely achieved, and treatment fails due to drug resistance. This project addresses the main challenges and limitations to making targeted therapies a true clinical success:
- Development of drug resistance during treatment
- Limitations of current standard tumor profiling approaches, which are not optimized to detect drug-resistant cells.
Researchers involved in this project use new single-cell sequencing technologies to gain maximum information on how different cell populations within a tumor reprogram their survival mechanisms to evade targeted therapies. To study treatment failure, the ENCOURAGER team models the disease and simulates treatment effects in the lab. Additionally, they will study glioma samples from patients who received targeted therapies, comparing those who responded to those who did not benefit from the treatment. This project focuses on pediatric gliomas, but successful development of this approach could accelerate its application to other high-risk pediatric cancers. By exploring the origins of drug resistance in-depth, the changes occurring in each tumor cell will be scrutinized to understand how they overcome advanced therapies. Another aspect of this project aims to improve the effectiveness of these therapies and prevent treatment failure by targeting cellular programs that promote therapeutic resistance. The knowledge gained from this program will enable clinical trials to better implement these targeted therapies, improving the prognosis for children and adolescents with high-grade gliomas.
Summary of ENCOURAGER
- Coordinating Investigators: Dr. Ana S. Guerreiro Stücklin
- Program Duration: January 2024 – January 2026
- Countries Involved: France, Switzerland
- Fight Kids Cancer Funding: €500,000, including €181,275 from Imagine for Margo
