TY - JOUR
T1 - Patient- and xenograft-derived organoids recapitulate pediatric brain tumor features and patient treatments
AU - Lago, Chiara
AU - Federico, Aniello
AU - Leva, Gloria
AU - Mack, Norman L.
AU - Schwalm, Benjamin
AU - Ballabio, Claudio
AU - Gianesello, Matteo
AU - Abballe, Luana
AU - Giovannoni, Isabella
AU - Reddel, Sofia
AU - Rossi, Sabrina
AU - Leone, Nicolas
AU - Carai, Andrea
AU - Mastronuzzi, Angela
AU - Bisio, Alessandra
AU - Soldano, Alessia
AU - Quintarelli, Concetta
AU - Locatelli, Franco
AU - Kool, Marcel
AU - Miele, Evelina
AU - Tiberi, Luca
N1 - Publisher Copyright:
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
PY - 2023/12/7
Y1 - 2023/12/7
N2 - 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.
AB - 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.
KW - brain tumors
KW - organoids
KW - patient-derived
KW - pediatric cancer
KW - translational applications
UR - http://www.scopus.com/inward/record.url?scp=85178430589&partnerID=8YFLogxK
U2 - 10.15252/emmm.202318199
DO - 10.15252/emmm.202318199
M3 - Article
C2 - 38037472
AN - SCOPUS:85178430589
SN - 1757-4676
VL - 15
JO - Embo Molecular Medicine
JF - Embo Molecular Medicine
IS - 12
M1 - e18199
ER -