This trial on pediatric neuroblastomas was co-funded by the Enfants sans Cancer 2021 race and was selected as part of our European Fight Kids Cancer grant call.


About Neuroblastomas in Children

Neuroblastoma is an extracranial malignant tumor that develops from primitive nerve cells called neuroblasts, which normally form nerve cells in 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 generally diagnosed before the age of five (90% of cases). More than half of the children have 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 onset.

Learn more about this disease: [link]


About Combalk

The development of personalized molecular medicine holds promise for all children and adolescents with high-risk or relapsed cancer. Currently, targeting specific genetic alterations in tumors using targeted drugs is the focus of numerous experimental clinical trials in pediatrics. Specifically, the ALK inhibitor Lorlatinib is entering phase III clinical evaluation in combination with chemotherapy for the treatment of neuroblastoma (SIOPEN-HR2 trial, which plans to recruit 800 children with high-risk neuroblastoma). ALK is a protein heavily involved in many cancers, and its activation maintains the cell in a proliferative state. However, patients are likely to develop resistance to treatment over time.

This project aims to understand the evolution of resistance to Lorlatinib and to counter it with an effective therapeutic combination. Researchers involved in this project will individually track the evolution of tumor cells in vivo. High-throughput sensitivity tests will then be used to test a battery of drugs to anticipate and target mechanisms of resistance to Lorlatinib combined with chemotherapy.


Project Progress

Researchers have identified two promising combinations that increase the likelihood of achieving a complete response in ex vivo models. They are currently studying the therapeutic effect and potential resistance mechanisms of these combinations, particularly in vivo, before potentially moving to clinical trials.


Summary of the COMBALK Project

  • Promoter: Institute of Cancer Research, UK
  • Principal Investigator: Louis Chesler
  • Fight Kids Cancer Funding: €500,000, including Imagine for Margo funding: €300,799
  • Countries involved: United Kingdom, France
  • Duration: September 2022 – September 2025