A three-dimensional experimental system has been developed to study the response to drugs in low-grade gliomas, a common central nervous system tumor in children. The project, developed by the University of Trento, the Bambino Gesu Children’s Hospital and the Sapienza University of Rome, is a breakthrough in the research, understanding and treatment of this disease. The results have just been published in an international journal molecular cancer.
Gliomas are tumors of the central nervous system that originate from glial cells that support neurons in the brain. Gliomas, which are less aggressive and slow to grow, are more common in children and young people. Glial tumors alone account for nearly 40% of all tumors in the central nervous system. Although low-grade gliomas are less malignant than other gliomas, they are still difficult to interpret biologically.
The scientific community is working to understand each of the many dark aspects of this disease and develop more targeted and effective treatments. The results of this Italian study have just been published in an international journal molecular canceris a breakthrough in research to better understand the mechanisms underlying disease onset, progression, and progression and to design new treatments.
The researchers are particularly focused on replicating the heterogeneity of low-grade pediatric gliomas in experimental systems. For this purpose, organoids of the human forebrain, the most anteriorly developed part of the brain, had already been developed. Organoids are three-dimensional cell cultures, small structures that at least partially replicate human organs. In this case, the researchers tried to recreate the part of the brain they were studying in the lab to better understand the disease. The use of organoids allows for the observation of diseases in a more realistic environment compared to monolayer cell cultures, which can improve drug screening before conducting clinical trials in patients. So a group of researchers developed organoids from pluripotent stem cells, which can differentiate into nearly every type of cell in the body, and used them to generate tumors.
Luca Tiberi, professor in the Department of Cellular, Computational, and Integrative Biology at the University of Trento and director of the Sibio Division at the Armenis Harvard Institute for Brain Disorders and Cancer Research, reports: With glioma. He continued, “These organoids allow us to study a variety of important stages, replicating some features of both human brain and glioma development under normal conditions.However, because organoids lack an immune system, vasculature, metabolism, and are not connected to a complete organism, they still have significant There are limitations. Blood vessels in particular are essential not only for the transport of nutrients and oxygen, but also for establishing metabolic and cellular interactions that are important for cell development.” Overall, these gaps prevent us from studying the various contributions to tumor development and growth, as well as the response of tumors to external stimuli. Without all the components, organoids provide only part of the biology of gliomas and their mechanisms. ”
Importantly, Bambino Gesu Children’s Hospital participated in the study of the molecular and epigenetic characterization of the system and its response to drugs, strengthening the link between experimental research and clinical practice.
“These experimental research systems represent a fundamental step towards more reliable preclinical systems for pediatric tumors,” said Evelina Miele from the Oncology Hematology, Cell Therapy, Gene Therapy and Hematopoietic Transplantation Unit. “We showed that the organoids reproduced the molecular features of low-grade gliomas slightly more faithfully and more closely resembled patients’ tumors compared to cells cultured in monolayers.” Miele also highlights the translational value of this study. “The potential to integrate molecular profiles such as DNA methylation and gene expression in the study of drug response makes these systems particularly important for preclinical research. She added: “These can improve the selection of therapeutic strategies and contribute to the development of more targeted approaches, especially in cancers such as low-grade childhood gliomas, where limited experimental systems have been available.”
“The Sapienza University of Rome contributed to this work by choosing a targeted experimental strategy and characterizing the immunohistochemical profile of the model, that is, by studying in detail the proteins expressed by the cancer cells,” explains Professor Elisabetta Ferretti from the Department of Experimental Medicine at the Sapienza University. “This is a true team effort with colleagues from the departments of Radiology, Oncology and Anatomical Pathology who have been working on brain tumor research for many years, following the work of our common mentor and inspiration, Professor Felice Giangaspero. He laid the foundation for our ongoing research. We are very pleased to have collaborated to create an experimental system for the study of low-grade childhood gliomas that will help us better understand this disease and guide future treatments.”
The goal is to overcome the current limitations of organoids. “Our study lays the foundation for a platform that increasingly expresses patient heterogeneity and patient response to treatment over time,” concludes Tiberi. “Our immediate goal is to achieve an increasingly reliable experimental system from both a physiological and clinical point of view for pediatric glioma research.”
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DOI: 10.1186/s12943-026-02612-x
