Evaluation of radioresponse and radiosensitizers in glioblastoma organotypic cultures

Abstract

Glioblastoma (GBM), a deadly primary brain malignancy, manifests pronounced radioresistance. Identifying agents that improve the sensitivity of tumor tissue to radiotherapy is critical for improving patient outcomes. The response to ionizing radiation is regulated by both cell-intrinsic and -extrinsic mechanisms. In particular, the tumor microenvironment is known to promote radioresistance in GBM. Therefore, model systems used to test radiosensitizing agents need to take into account the tumor microenvironment. We recently showed that GBM explant cultures represent an adaptable ex vivo platform for rapid and personalized testing of radiosensitizers. These explants preserve the cellular composition and tissue architecture of parental patient tumors and therefore capture the microenvironmental context that critically determines the response to radiotherapy. This chapter focuses on the detailed protocol for testing candidate radiosensitizing agents in GBM explants.