Brain tumors are the leading cause of cancer-related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancers are limited and hard to establish. We present a protocol that enables efficient generation, expansion, and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient-derived organoids (PDOs) from ependymomas, medulloblastomas, low-grade glial tumors, and patient-derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles, and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine.

Patient- and xenograft-derived organoids recapitulate pediatric brain tumor features and patient treatments / Lago, Chiara; Federico, Aniello; Leva, Gloria; Mack, Norman L; Schwalm, Benjamin; Ballabio, Claudio; Gianesello, Matteo; Abballe, Luana; Giovannoni, Isabella; Reddel, Sofia; Rossi, Sabrina; Leone, Nicolas; Carai, Andrea; Mastronuzzi, Angela; Bisio, Alessandra; Soldano, Alessia; Quintarelli, Concetta; Locatelli, Franco; Kool, Marcel; Miele, Evelina; Tiberi, Luca. - In: EMBO MOLECULAR MEDICINE. - ISSN 1757-4676. - 15:12(2023), pp. 1-28. [10.15252/emmm.202318199]

Patient- and xenograft-derived organoids recapitulate pediatric brain tumor features and patient treatments

Soldano, Alessia;
2023-01-01

Abstract

Brain tumors are the leading cause of cancer-related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancers are limited and hard to establish. We present a protocol that enables efficient generation, expansion, and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient-derived organoids (PDOs) from ependymomas, medulloblastomas, low-grade glial tumors, and patient-derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles, and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine.
2023
15
12
1
28
e18199
10.15252/emmm.202318199
https://pubmed.ncbi.nlm.nih.gov/38037472/
Lago, Chiara; Federico, Aniello; Leva, Gloria; Mack, Norman L; Schwalm, Benjamin; Ballabio, Claudio; Gianesello, Matteo; Abballe, Luana; Giovannoni, Isabella; Reddel, Sofia; Rossi, Sabrina; Leone, Nicolas; Carai, Andrea; Mastronuzzi, Angela; Bisio, Alessandra; Soldano, Alessia; Quintarelli, Concetta; Locatelli, Franco; Kool, Marcel; Miele, Evelina; Tiberi, Luca
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/135320
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