Paediatric brain tumours: molecular switch that slows growth discovered
Medulloblastoma, one of the most aggressive paediatric brain tumours, is a disease characterised by marked biological heterogeneity, requiring personalised therapeutic strategies. Like other tumours associated with high MYC oncogene activity, medulloblastoma is often resistant to currently available treatments (surgery combined with radiotherapy and chemotherapy).
Understanding the metabolic mechanisms that underpin its progression is therefore a crucial step in the development of new, more effective and less toxic therapies.
An international study, coordinated by Olivier Ayrault of the Institut Curie in collaboration with Sapienza University of Rome, the Pasteur Institute Italy Cenci Bolognetti Foundation and other international institutes such as Baylor College of Medicine in Houston, identified a new molecular mechanism involved in medulloblastoma growth. The research results were published in the prestigious journal Cancer Cell.
The authors examined clinical data and tumour samples from approximately 400 paediatric patients with medulloblastoma, constituting one of the largest cohorts available internationally.
To characterise this tumour as comprehensively as possible, researchers analysed not only DNA, but also messenger RNA, proteins and metabolites present in the cell. Studies have shown that tumour cells accumulate lipids in the form of lipid droplets, which are used as an energy reserve to support cell proliferation and survival.
The results of the research show that, in medulloblastomas characterised by MYC activation, blocking lipid synthesis is not sufficient to inhibit tumour growth, as neoplastic cells are able to compensate by importing lipids from the extracellular environment.
However, this metabolic adaptation mechanism can be slowed down by inhibiting the DGAT1 enzyme, which is involved in the formation of lipid droplets, resulting in a significant reduction in tumour growth and improved survival in experimental models.
The results of the study therefore identify a new metabolic vulnerability in the most aggressive subtypes of medulloblastoma and lay the foundations for the development of targeted therapeutic strategies, with potential implications for improving the effectiveness of treatments and reducing side effects in paediatric patients.
The work represents a significant example of international scientific collaboration. The co-first authors of the study (Flavia Bernardi and Irene Basili) obtained their PhDs in Molecular Medicine at the Department of Molecular Medicine of Sapienza University, conducting their research in the Pasteur-affiliated laboratory of Professor Lucia Di Marcotullio, co-author of the study.
References:
Flavia Bernardi et al. (2026) Multiomic integration reveals tumoral heterogeneity of lipid dependence within lethal group 3 medulloblastoma. Cancer Cell 41544627. DOI: https://doi.org/10.1016/j.
Further Information
Lucia Di Marcotullio - Department of Molecular Medicine