Researchers are at work to find effective treatments to help young patients with brain tumors. Hundreds of brain organoids have been developed in the laboratories of the University of Trento to understand the genetic mechanisms responsible for medulloblastoma, the most common brain cancer affecting children.

“Creating brain tumor organoids is very difficult, and requires the specific scientific capabilities that the Cibio department managed to attract and develop in its research laboratories. Organoids generated from skin or blood cells and shaped like irregular spheres the size of a small peanut were grown by the University of Trento and examined and characterized with Sapienza University of Rome and Ospedale pediatrico Bambino Gesù in Rome. They can show signs of disease and provide a model of the tumors affecting young patients,“

said Luca Tiberi of the Armenise-Harvard Laboratory of Brain Disorders and Cancer at the University of Trento.

Two Key Proteins

The organoids were used to create in vitro tumor models, and the results will make it possible to advance brain cancer research, as in the near future, the large-scale production of in vitro tumors could provide a low-cost method for screening new drugs.

The research team included personnel from Sapienza University of Rome, Ospedale pediatrico Bambino Gesù in Rome, and Irccs Neuromed-Istituto neurologico mediterraneo in Pozzilli (Isernia).

“We have also grown organoids from the cells of healthy donors, and these gave us the opportunity to understand some of the genetic mechanisms responsible for the onset and development of brain tumors. In particular, the study confirmed the key role of two proteins (Otx2 and c-Myc) and investigated the efficacy of a number of therapeutic options (based on the drug Tazemetostat). These in vitro tumors will help us fine-tune research on the genes that cause cancer and on possible prevention and treatment strategies. Organoids give us the opportunity to study brain tumors without using experimental animals in a context that is similar to a real-patient scenario. They can be a reliable tool for developing personalized therapies.“

said Tiberi.

[caption id="attachment_102247” align="aligncenter” width="700”] (a) DAPI fluorescent staining and GFP immunofluorescence of CD1 mouse brain section 3 months after transfection with pPBase + pPBMyc + pPBGfi1 + pPBVenus at P0.
(b) DAPI and GFP immunofluorescence of CD1 mouse brain section 1 month after transfection with pPBase + pPBMyc + pPBOtx2 + pPBVenus at P0.
(c) Hematoxylin and Flag (Gfi1) immunohistochemistry of CD1 mouse tumors after transfection with pPBase + pPBMyc + pPBGfi1 + pPBVenus at P0.
(d) DAPI and Otx2 immunofluorescence of CD1 mouse brain section 1 month after transfection with pPBase + pPBMyc + pPBOtx2 + pPBVenus at P0.
Credit: Ballabio, C., et al. CC-BY[/caption]

Medulloblastoma

Brain tumors are the first cause of death from cancer in children. They are very aggressive and require a multidisciplinary and integrated approach.

While significant progress has been made in treating these tumors, surviving patients may suffer long-term side effects that significantly compromise their quality of life. When the tumor reappears after some time, therapies are usually ineffective.

Medulloblastoma, the focus of this study, is the most common malignant brain tumor in children affecting the central nervous system. The survival rate at five years from the diagnosis of medulloblastoma is around 70 percent.

Current available treatment for medulloblastoma consists of maximal safe resection, craniospinal radiation (for children ≥ 3 years old) and chemotherapy.

[1] Ballabio, C., Anderle, M., Gianesello, M. et al. Modeling medulloblastoma in vivo and with human cerebellar organoids. Nat Commun 11, 583 (2020). https://doi.org/10.1038/s41467-019-13989-3


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