Breakthrough in Pediatric Brain Cancer: International Team Unveils “Fuel Tank” Vulnerability in Medulloblastoma
An international study led by the Institut Curie in collaboration with the Istituto Pasteur Italia Cenci Bolognetti Foundation –Sapienza University and other international academic institutions, including the Baylor College of Medicine in Houston, has revealed a new molecular mechanism to block the growth of medulloblastoma, the most common malignant brain tumor in children. The results of this work, which identify “lipid droplets” as a critical and targetable vulnerability, have been published in the prestigious journal Cancer Cell
Medulloblastoma exhibits significant biological complexity that demands personalized therapeutic strategies. In particular, tumors characterized by high activity of the MYC oncogene are often resistant to conventional treatments. Understanding the metabolic mechanisms that regulate their progression is a crucial point in the development of new, less toxic, and more effective personalized interventions.
The research was led by Olivier Ayrault (Institut Curie), who is a member of the Board of Professors for the PhD program in Molecular Medicine at Sapienza University of Rome. The laboratory of Dr. Ayrault assembled clinical and omics data from 384 primary medulloblastoma from France, US, Canada and Germany, with two main objectives: to better understand why 20% of children still do not survive and to limit the toxic side effects of chemotherapy.
“We chose an integrated research approach, explain Drs. Ayrault and Basili (Co–first author and recipient of a prestigious fellowship for research abroad awarded by Istituto Pasteur Italia), “meaning that we characterize this tumor as throughly as possible by sequencing not only the DNA but all molecular elements within the cell, including messenger RNA, proteins, and metabolites”. By integrating the largest multi-omics dataset generated to date in cancer, combining five biological layers from 384 patient samples, the team demonstrated that tumor cells survive by creating intracellular “fuel tanks” known as lipid droplets.
The study reveals how aggressive tumors fueled by MYC survive by creating these microscopic droplets to store energy and evade treatments. While traditional treatments often fail because cancer cells find “escape routes” to gather nutrients, the researchers found that blocking the production of new fats is insufficient in medulloblastoma because the tumor compensates by importing lipids from the surrounding environment. However, by targeting an enzyme called DGAT1, a key regulator of lipid droplet formation, the team successfully disrupted this storage system. This inactivation triggers a cascade of events that leads to the blockage of tumor growth and significantly improves survival in experimental models.
This breakthrough discovery highlights a significant bridge between French and Italian scientific training. The co-first authors of the study (Drs. Flavia Bernardi and Irene Basili) are former PhD students from the Department of Molecular Medicine at Sapienza University of Rome, having conducted their doctoral research in the laboratory of Lucia Di Marcotullio, affiliated to Istituto Pasteur Italia, co-author of the present study.
This discovery offers hope for new, more precise therapies for currently untreatable subtypes of medulloblastoma. By identifying this Achilles’ heel downstream of MYC, the study opens the way for a new therapeutic strategy aimed at overcoming drug resistance and turning the cancer’s own survival strategy against itself.
Image credits: Illustration © Biopixia
