Understanding high-risk glioma cancer, cell by cell

This project was selected in the framework of our fourth European call: FIGHT KIDS CANCER 2023. It is jointly financed by Imagine for Margo, Kriibskrank Kanner Fondatioun, CRIS Cancer Foundation, KiKa and KickCancer.

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Brain tumours are among the most common and deadly solid tumours in children, adolescents, and young adults. Despite improvements in treatments such as chemotherapy, surgery and radiation therapy, the outlook for patients with a high-risk tumour is poor. In recent years, there has been little progress in the development of new drugs for brain tumours, including gliomas.

The ability to detect molecular changes in tumours has led to improved therapies, which act by disrupting cancer-specific mutations. These targeted therapies are now increasingly used in clinic, often as personalised treatment attempts for children with high-risk cancers, who have exhausted all other standard therapeutic options. Meaningful responses to targeted therapies are seen in some but not all patients. Even when patients respond to treatment, long-term tumour control is rarely achieved, and treatment fails after a time as cancer cells start developing resistance to the novel targeted drugs.

This study aims to understand this development of drug resistance during treatment and optimise the current standard tumour profiling approaches to increase detection of drug-resistant cells.

Researchers will sequence the tumour at a single-cell level. This will help to understand how, within a tumour, different cell populations reprogram their survival strategies to escape targeted therapies. Both the disease and mimic treatment will be modelled in a lab: researchers will compare glioma tumour samples from patients that responded to targeted therapies to those that did not. Such an in-depth approach will hopefully enable to capture changes in individual cells to understand how those cells overcome the most cutting-edge therapies.

This study aims to increase the efficacy of these therapies and prevent treatment failure. This knowledge can be used to refine therapy, enabling clinical trials to improve the selection and implementation of targeted therapies, with the ultimate objective to improve survival for children and adolescents with high-risk cancers.