Development of a Murine Intracranial Surgical Resection Glioblastoma Model to Facilitate Preclinical In Vivo Drug Screening

Background: Current murine glioblastoma (GBM) models do not incorporate tumor resection and thus do not allow study of recurrent GBM after surgery, including postsurgical changes in the tumor microenvironment (TME), thereby limiting translational relevance. Methods: In phase 1 of a three-phase study, we compared tumor cell implantation into a cavity created using conventional microdissection techniques or the Myriad Research Laboratory System (MRLS) versus direct implantation into the brain without a cavity, and assessed morbidity using the neurological severity score (NSS). In phase 2, we developed a new surgical resection model, the Surgical murine GBM resection model (Sur-rGBM), and examined the effects of tumor resection on the tumor microenvironment (TME) and on overall survival. In phase 3, we compared the therapeutic response to temozolomide (TMZ) with or without anti-VEGF antibody, after resection (Sur-rGBM) or no resection. Tumor growth was confirmed before and after resection by ultrasound. Animals were euthanized for immunohistochemical assessment at maximal tumor growth. Results: Creating a cavity for tumor cell implantation using MRLS improved survival compared to direct cell injection with no cavity. Tumor resection increased survival, and TMZ combined with an anti-VEGF antibody after tumor resection improved survival compared with surgery or TMZ alone. Resection induced significant changes in biomarker expression within the TME. Conclusions: Our novel murine GBM surgical resection model (Sur-rGBM) provides reliable, controlled tumor growth and a standardized resection technique to facilitate studies on TME changes and therapeutic response after tumor resection.