The development of effective treatments for malignant brain tumors has been hampered by the lack of robust preclinical models that faithfully capture the high inter- and intra-tumor heterogeneity of the human disease. Conventional cell lines lose the most common genetic aberrations of glioblastoma (GBM), while primary cultured cells (gliomasphere models) do not account for the influences of the microenvironment and the blood brain barrier on tumor biology and drug efficacy. These systems are also under strong selection pressure divergent from that in vivo, leading to reduced clonal heterogeneity and an overall shift away from the characteristics of GBM. Our project aims to create a biobank of direct-from-patient derived orthotopic xenografts (GliomaPDOX) that preserve the diverse genetic and transcriptional landscapes found in human GBMs. Further, we hope to utilize both orthotopic xenograft and gliomasphere model systems as an opportunity to learn more about the influences of the tumor microenvironment, intratumoral heterogeneity, and developmental hierarchies on GBM tumorigenesis. Our preliminary findings support GliomaPDOX as a model system that preserves the defining molecular and anatomic characteristics of GBM and is well-suited for translational research investigations.

Team Members and Collaborators