Neuroblastomas in Children
A neuroblastoma is an extracranial malignant tumor that develops from primitive nerve cells, called neuroblasts, which normally form the nerve cells of the body. This type of solid tumor is one of the most common in children.
This disease represents 10% of solid tumors in children under 15 years old and mainly affects young children, as it is usually diagnosed before the age of five (90% of cases). More than half of the children have a disease that is metastatic at the time of diagnosis. The exact causes of neuroblastoma are unknown, but it seems that genetic and environmental factors play a role in its onset.
About the Project
The LIMK protein family (LIMK1 and LIMK2) are central regulators of cellular cytoskeletal dynamics (cell architecture). They modulate both the stability and growth of this essential component for the life of every cell. The production of LIMK1 and/or LIMK2 is elevated in a large number of cancers, and multiple studies have shown their contribution to metastatic invasion. Furthermore, LIMKs contribute to the resistance of certain cancers to chemotherapeutic agents, particularly those targeting the cytoskeleton or preventing the proliferation of cancer cells. This is precisely the case with neuroblastoma, which is treated initially with a cocktail of therapeutic agents, including some like vincristine that act directly on the cytoskeleton. Interestingly, a recent study conducted on cultured cells showed that those originating from neuroblastomas are among the most sensitive to molecules targeting LIMK.
This project aims to test the molecule CEL-001 in a new model of high-risk neuroblastoma. It is a collaboration between the NeuroMyoGene Institute (CNRS), the company Cellipse which produces the molecule, and Oncofactory, which develops a model to replicate patient tumors in an immature organism – the avian embryo – and this in a very short time (from 48 hours to 7 days). Furthermore, OncoFactory has validated the possibility of analyzing, through 3D imaging techniques, the anti-tumor efficacy of candidate molecules.
This study involved adapting the doses of CEL-001 inoculated in the avian model of neuroblastoma. 3 doses of CEL-001 were tested alone and in combination with vincristine, a common chemotherapy for this pediatric cancer. This allowed observing the effectiveness of this treatment on neuroblastoma cells inoculated in the egg and its toxicity on the development of the avian embryo. Although the combined effect of these two molecules showed promising potential on neuroblastoma cells in culture and these two molecules did not prove toxic to embryonic development, however, the study did not reveal any therapeutic gain of CEL-001 compared to vincristine (alone or in combination).
Project Summary
- Promoter: NeuroMyoGene Institute
- Principal Investigator: Dr. Valérie Castellani
- Program Duration: 2018-2020
- Countries Involved: France
- Funding from Imagine for Margo: €25,000
