Patient-derived and xenograft-derived organoids for characterization, drugs testing and biobanking of pediatric brain tumors

Central nervous system (CNS) tumors are the most common solid tumors in the pediatric population and the leading cause of death among childhood cancers. They present common features related to the development and produce symptoms based on their location, rate of tumor growth and age of the child. Tumors of embryonal origin, such as medulloblastoma or primitive neuroectodermal tumor, have a higher incidence in younger patients, whereas older ones tend to present tumors of glial origin. Most of CNS-embryonal tumors are highly malignant and consequently leading to poor prognoses. Despite the understanding of the underlying molecular landscape of these tumors that has helped in clinical advances to improve life expectancies of the patients, there is still an emerging need to minimize morbidity and manage the long-term therapy effects. Developing new models to better understand the complexity and heterogeneity of these tumors and to test personalized treatment strategies remains a clinical challenge. We are trying to answer to this medical need with Patient-Derived Organoids (PDOs) and Patient- Derived Xenograft Organoids (PDXOs) established through the direct in vitro culture of primary tumors and patient derived xenograft (PDX)-derived tumors. We have developed a method for generating PDOs from a variety of pediatric brain cancers (ependymoma, medulloblastoma and low-grade glial tumors) that recapitulates the cellular heterogeneity, histological features, and mutational profiles of the corresponding parental tumors. We have obtained promising results from the DNA methylation profile analysis, nowadays used for an accurate routine diagnosis of CNS tumors. Through these new models, we confirmed the action of clinically applied therapeutic regimens, obtaining a proof of concept of their possible application as a reliable tool for personalized medicine, drug screening and development of newer and more specific therapeutic strategies.

Grantor dc:publisher

Università degli studi di Trento

Year dc:date

2023

Author dc:creator

• Lago, Chiara

Statement dc:rights

• info:eu-repo/semantics/openAccess
• license:Tutti i diritti riservati (All rights reserved)
• license uri:iris.PRI01

Language dc:language

eng

Identifier

http://dx.doi.org/10.15168/11572_383190
10.15168/11572_383190

OAI identifier oai:identifier

oai:iris.unitn.it:11572/383190