SURG-37. ADVANCING GLIOBLASTOMA RESEARCH THROUGH RESECTION MODELS

Abstract Regardless of its cellular and molecular heterogeneity, glioblastoma (GBM) tumors share a common hallmark: an infiltrative growth pattern that poses challenges to surgical resection and leads to incomplete tumor removal. As part of the current standard-of care treatment, patients undergo surgery in addition to temozolomide and radiation therapy. In GBM research, mice are often used to replicate tumor development and test treatments, but this approach typically omits the crucial aspects of surgical intervention, and thus fails to recapitulate important aspects of human GBM disease progression at the surgical margin. Here we address this challenge by developing a technique for tumor resection in mice. First, we implant the infiltrative patient derived GBM cell line Akaluc G16302 in the frontal cortex, specifically at anteroposterior 2mm, mediolateral 0.5mm, dorsoventral 1mm starting from bregma. After 6 weeks, we anesthetize the mouse and do a craniotomy at the injection site, approximately 3-4mm in diameter. We perform a circumferential cut using a curved Fukushima scissor at the edges of the craniotomy area and scoop the tumor core, mimicking surgical resection. Mice survive the surgery and are alive up to 37 days post-resection. Histology confirms resection of tumor cells and a surgical tumor margin remaining in the xenograft animal. In our pilot study, mice undergoing resection displayed significantly increased overall survival compared to mice without surgery (log-rank p-value = 0.0448; n=6; survival range of 91-100 days for control and 97-107 days for resected mice), recapitulating survival benefit also seen in humans. This preliminary data demonstrates the feasibility of the technique and resection-associated survival benefit. Such advancements enable researchers to more accurately replicate the biology of GBM progression and treatment response observed in human patients, bringing us closer to modeling the clinical scenario in mice. Key words: Glioblastoma, resection, biopsy