BIOL-02. MODELING BRAIN TUMORS IN VIVO AND WITH HUMAN ORGANOIDS

Abstract

Abstract Brain tumors are a large and heterogeneous group of neoplasms that affect the central nervous system and include some of the deadliest cancers. Almost all the conventional and new treatments fail to hinder tumoral growth of the most malignant brain tumors. This is due to multiple factors, such as intra-tumor heterogeneity, the microenvironmental properties of the human brain, and the lack of reliable models to test new therapies. Therefore, creating faithful models for each tumor and discovering tailored treatments pose great challenges in the fight against brain cancer. We have recently developed a human IPSCs-derived organoid model of pediatric medulloblastoma and pediatric high-grade glioma. These models overcome the limitations of using animal models and pave the way to gaining unprecedented new knowledge into the development of brain cancer in a human system. Nevertheless, to fill the gap in the brain cancer field it will be crucial to use patient-derived tissues. To this aim, in the next years, we will develop patient-derived organoids (PDO) of pediatric brain tumors. These organoids recapitulate several features of the primary human tumors, such as intra-tumor heterogeneity and genomic alternation. The production of PDOs will allow us to generate important new knowledge, discover of potential drug targets, and small molecules that could be exploited in early-phase clinical trials, hopefully, to develop and validate new treatments. Interestingly, the possibility of using organoids directly generated from pediatric tumors will also pave the bases for personalized therapies.