A three-dimensional experimental system has been developed to study the response to drugs in low-grade glioma, a tumor of the central nervous system that often occurs in children. The project, developed by the University of Trento, Bambino Gesù Children's Hospital and Sapienza University of Rome, is a breakthrough in the study, understanding and treatment of the disease. The results have just been published in the international journal Molecular Cancer .
Glioma is a tumor of the central nervous system that originates from glial cells, which support neurons in the brain. In the less aggressive, slow-progressing forms, gliomas are often found in children and youth. Glial tumors alone make up almost 40% of all tumors of the central nervous system. Low grade gliomas are less aggressive than others, but still difficult to interpret biologically.
The scientific community is committed to understand, one by one, the numerous dark sides of the disease and to develop more targeted and effective treatments. The results of this Italian study, just published in the international journal Molecular Cancer , are a leap forward in research to better understand the onset, progression and mechanisms underlying the progression of the disease and to design new therapies.
Researchers have focused in particular on trying to reproduce the heterogeneity of low-grade pediatric glioma in an experimental system. For this purpose, organoids of the human forebrain, the most anterior and developed part of the brain, had already been developed. Organoids are three-dimensional cell cultures, miniature structures that replicate, at least in part, human organs. In this case, the research team tried to reproduce in the laboratory the part of the brain to be investigated to better understand the disease. The organoids make it possible to observe the disease in a slightly more realistic environment, compared to single-layer cell cultures, and to improve drug screening before carrying out clinical trials with patients. The group of researchers has therefore developed organoids from pluripotent stem cells, which are capable of differentiating into almost all types of cells in the body, and used them to develop the tumor.
Luca Tiberi, professor of the Department of Cellular, Computational and Integrative Biology of the University of Trento and head of the Armenise Harvard Laboratory of Brain Disorders and Cancer at the Cibio Department, reports: "In the study, we create a system in which to study low-grade tumors. The path we have taken is based on organoids that we generate in the laboratory from pluripotent cells. Once we have generated the brain organoids, we make them sick with glioma." He continues: "In these organoids we can reproduce some characteristics of the development of both the human brain, under normal conditions, and the glioma, to examine various important phases. Organoids however still have considerable limitations, as they do not have an immune system, a vascular system, no metabolism, and are not connected to a complete organism. Blood vessels, in particular, are essential not only for the transport of nutrients and oxygen, but also to establish metabolic and cellular interactions that are crucial for the development of the tumor. Overall, these gaps prevent us from studying the different contributions to tumor onset and growth, as well as the tumor's response to external stimuli. Without all the components, organoids provide only a partial representation of glioma biology and its mechanisms."
Crucially, the Bambino Gesù Children's Hospital participated in the molecular and epigenetic characterization of the systems and in the study of the response to drugs, strengthening the connection between experimental research and clinical practice.
"These experimental study systems represent a fundamental step towards more reliable preclinical systems for pediatric tumors," says Evelina Miele, of the Onco-Hematology, Cell Therapy, Gene Therapies and Hemopoietic Transplant Unit. "We have shown that organoids reproduce in a slightly more faithful way the molecular characteristics of low-grade gliomas, compared to cells in single-layer culture, and are more similar to the patients' tumors." Miele also underlines the translational value of the work: "The possibility of integrating molecular profiles, such as DNA methylation and gene expression, in the study of drug response, makes these systems particularly important for preclinical research. In fact, they allow us to more accurately evaluate the effectiveness of treatments before their experimental use in patient studies." She adds: "They can improve the selection of therapeutic strategies and contribute to the development of more targeted approaches, especially in cancers such as low-grade pediatric gliomas, for which the experimental systems available until now were limited."
"Sapienza University of Rome contributed to the study by selecting targeted experimental strategies and characterizing the immunohistochemical profile of the models, that is, by studying in detail the proteins expressed by cancer cells," explains Elisabetta Ferretti, professor of the Department of Experimental Medicine of Sapienza University. "It was a real team effort with colleagues from the Department of Radiological, Oncological and Anatomical Pathological Sciences, who have been working on brain tumors for years, following the work of our common mentor and inspiration, Professor Felice Giangaspero, who laid the foundations of our ongoing research. We are very happy to have helped to create experimental systems for the study of low-grade pediatric glioma that will help to better understand this disease and guide future therapies."
The goal is to overcome the current limits of organoids. "Our work lays the foundations for platforms that are more and more representative of the heterogeneity of patients and their responses to treatments over time," concludes Tiberi. "The horizon for us now is to achieve increasingly reliable experimental systems, from a physiological and clinical point of view, for research on pediatric glioma."
Funding and article information
The project received funding from Fondazione Giovanni Armenise-Harvard; Fondazione Cassa di Risparmio di Trento e Rovereto; Fondazione Airc for Cancer Research; Fight Kids Cancer; European Molecular Biology Organization (Embo); Fondazione Pezcoller. The Core Facilities of the Cibio Department are supported by the European Regional Development Fund.
The article "Modeling Pediatric Low-Grade Glioma Heterogeneity Using Human Forebrain Organoids" was published in Molecular Cancer, with Evelina Miele (Bambino Gesù Children's Hospital in Rome), Elisabetta Ferretti (Sapienza University of Rome) and Luca Tiberi (University of Trento) as main authors, and Gloria Leva and Lucia Santomaso (PhD students at the University of Trento) as first authors.
Molecular Cancer
Experimental study
Lab-produced tissue samples
Modeling pediatric low-grade glioma heterogeneity using human forebrain organoids
1-Apr-2026