Stereotactic Intracranial Implantation of Glioblastoma Patient-derived Xenograft Cell Lines in Mice

The development of efficacious treatment regimens has been challenging for central nervous system tumors, in part due to the limited availability of translationally relevant preclinical models. Glioblastoma (GBM) is the most common and aggressive primary brain tumor and is the focus of this research. Established cell line-derived models do not accurately reflect the genetic heterogeneity of human diseases. This is of particular concern in the current landscape, where a majority of pharmaceuticals are targeting tumor-specific alterations. Moreover, studies that leverage subcutaneous xenografts are technically easier to execute, but the blood-brain barrier (BBB) is completely absent. As one of the features responsible for treatment failure in neuro-oncology, the BBB must be considered when evaluating any novel therapeutic strategy. Therefore, intracranial placement is of critical importance. We have established and characterized over 100 GBM patient-derived xenograft (PDX) intracranial models to support therapeutic evaluation efforts. Here, we describe the stereotactic implantation technique that we utilize for these studies.