Matching panels of in vivo and in vitro model system of pediatric brain tumors

Scope of Work – Northwestern University Feinberg School of Medicine The NIH/NCI U01 entitled “Matching panels of in vivo and in vitro model system of pediatric brain tumors” is aimed at exploring the similarities and differences of in vitro and in vivo models of brain tumors, especially as they are related to the original patient sample. The current mismatch in our understanding of in vivo and in vitro systems hinders preclinical drug testing. We propose to delineate the underlying biological mechanisms that drive the similarity and differences of phenotypes and dictate radiation induced responses in cancer stem cells between the in vitro and in vivo model systems by using PDOX models of medulloblastoma, high grade glioma, ependymoma and CNS germinoma. Given the critical roles of cancer stem cells in radiation resistance and frequent gene mutations involved in histone modification in pediatric brain tumors, we will explore responses of brain tumor stem cells to radiation, since they may not be identical as those in vivo and in vitro. The Northwestern University Feinberg School of Medicine subaward Co-Investigator Dr. Daniel J. Brat, will be subcontracted by Lurie Children’s Hospital to provide: Histologic assessment of PDOX models of brain tumors. There are multiple forms of brain tumors being investigated in this proposal and Dr. Brat is an expert in the neuropathologic classification of human brain tumors and is recognized for his work in tissue-based investigation. Dr. Brat will assist in the analysis of distinct cell populations within the tumor micro-environment of the PDOX models using immunohistochemical and molecular testing. Response to therapy will also be assessed histologically in specific histologic subtypes of PDOX, and the elements of the tumor micro-environment to these treatments will also be assessed using histology, IHC and molecular studies. The proposed work will be conducted during the period 12/01/2019 – 11/30/2024.