Scientists Identify Key Enzyme in Childhood Brain Tumor Growth, Paving Way for Targeted Therapies
A groundbreaking international study has pinpointed the Dgat1 enzyme as critical to the growth of medulloblastoma, the most common malignant brain tumor in children. Published in the journal Cancer Cell, the research offers a promising new avenue for developing more effective and less toxic treatments for this aggressive disease.
Medulloblastoma is a particularly challenging cancer, characterized by important biological differences between patients. This complexity necessitates personalized treatment approaches, as standard therapies – surgery, radiotherapy, and chemotherapy – often prove ineffective, especially in tumors with high activity of the Myc oncogene. Understanding the underlying metabolic processes fueling tumor progression is therefore paramount.
The study, a collaborative effort led by Olivier ayrault of the Institut Curie and involving researchers from Sapienza university of Rome, the Istituto pasteur Italia fondazione Cenci Bolognetti, and the Baylor College of Medicine in Houston, represents a significant leap forward. Researchers meticulously analyzed clinical data and tumor samples from approximately 400 pediatric patients – one of the largest cohorts of its kind globally.This complete analysis extended beyond DNA to include messenger RNA, proteins, and metabolites within the tumor cells.
The team discovered that medulloblastoma cells accumulate lipids in the form of lipid droplets,utilizing them as an energy reserve to drive cell proliferation and survival. However, the research revealed a surprising adaptation mechanism. In medulloblastomas with activated Myc, simply blocking lipid synthesis isn’t enough to halt tumor growth. These cancer cells can compensate by importing lipids from their surrounding environment.
“This metabolic adaptation mechanism can be slowed down by inhibiting the Dgat1 enzyme,” explained a lead researcher. “We observed a significant reduction in tumor growth and improved survival rates in experimental models when Dgat1 was inhibited.” this finding identifies a crucial metabolic vulnerability within the most aggressive subtypes of medulloblastoma.
The implications of this research are considerable. The study’s authors believe their findings “lay the foundations for the advancement of targeted therapeutic strategies,with potential implications for improving the effectiveness of treatments and reducing side effects in pediatric patients.” This represents a critical step towards more precise and less harmful cancer care for children.
The collaborative nature of this work underscores the importance of international scientific partnerships. Flavia Bernardi and Irene Basili, co-first authors of the study, completed their doctoral work in Molecular Medicine at Sapienza University, conducting their research in a laboratory affiliated with the Pasteur Institute, under the guidance of co-author Lucia Di Marcotullio. This research exemplifies how shared expertise and resources can accelerate progress in the fight against childhood cancer.
Why this research matters: Childhood medulloblastoma, a highly aggressive brain tumor, often resists standard treatments. Researchers sought to understand why some tumors are so resilient and identify new therapeutic targets.
Who was involved: The study was a collaborative effort led by Olivier Ayrault (Institut Curie) and included researchers from Sapienza university of Rome, the Istituto Pasteur Italia Fondazione Cenci Bolognetti, and the baylor College of Medicine. Flavia bernardi and Irene Basili were co-first authors.
What thay discovered: The team found that medulloblastoma cells, particularly those with high myc activity, rely heavily on lipids for energy. They discovered that inhibiting the Dgat1 enzyme, which regulates lipid metabolism, significantly slowed tumor growth and improved survival in experimental models.
How it ended (and what’s next): The research doesn’t represent a cure, but it identifies a crucial metabolic vulnerability. The findings pave the way for developing targeted therapies specifically designed to inhibit Dgat1, potentially offering a more effective and less toxic treatment option for children with aggressive medullo
