Research program led by Prof. Rogier Versteeg on combinatorial therapy to prevent fatal relapses in pediatric neuroblastoma.
Neuroblastomas in Children
A neuroblastoma is an extracerebral 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 cancer originates from the sympathetic nervous system (which prepares the body for intense activity) in the abdomen and sometimes in the adrenal glands located just above the kidneys, or along the spine. More rarely, this cancer can also develop in nerve ganglia located in the neck, chest, or pelvis.
This disease represents 10% of solid tumors in children under the age of 15 and primarily affects young children, as it is usually diagnosed before the age of five (90% of cases). More than half of the children present with metastatic disease at the time of diagnosis. The exact causes of neuroblastoma are unknown, but genetic and environmental factors are believed to play a role in its occurrence.
About Prevention of Neuroblastoma Relapse
In the majority of patients, the tumor reappears within five years. These relapses are resistant to therapy and have a fatal outcome. The current treatment for neuroblastoma is very effective in eradicating all the cells that make up the tumor, except for a very small number of them. These resistant cells are unfortunately responsible for recurrences, and it took time to identify them.
Five years ago, it was discovered that a neuroblastoma tumor cell could adopt two different forms: one resembling an immature cell type (mesenchymal type) and the other more like mature neuronal cells that produce adrenaline (adrenergic type). The two cell types have very different properties but can switch from one to the other. Mature, adrenergic-type cells can be killed by chemotherapy, but immature cells are resistant to it.
The project team recently identified that the protein TRAIL could target these immature mesenchymal neuroblastoma cells. It was shown that a therapy test combining this “drug” with the standard protocol significantly prevented relapses. However, it is unfortunately not possible to indicate this treatment for patients. A pharmaceutical company has provided the research team with a new generation of this drug, GEN1029, which reproduces the same effects as the TRAIL protein. In this project, the researchers will evaluate the ability of this new compound to prevent or delay relapses in different neuroblastoma models, notably in combination with lorlatinib, which targets the ALK pathway. The results of this project, especially if positive, could significantly improve the management of patients with relapsed neuroblastoma.
Project Progress
The initial results are very encouraging and show that the relapse was significantly delayed thanks to the combination (in vivo model). To refine these results, five new mouse relapse models are being generated. Thus, the results obtained on these five different models will provide essential knowledge before any clinical investigation.
Summary of the Prevention of Neuroblastoma Relapse Project
- Lead Investigators: Prof. Rogier Versteeg
- Program Duration: January 2023 – January 2025
- Countries Involved: Germany, Netherlands
- Funding by Fight Kids Cancer: €400,000, including funding by Imagine for Margo: €226,704
