Establishing a model for studying recurrent glioblastoma

Abstract

Introduction: Glioblastoma multiforme (GBM) is the most frequent malignant central nervous system neoplasm in adults. Current standard of care includes surgical debulking, followed by concurrent chemo- and radiotherapy. Unfortunately, response to treatment is transient and prognosis is poor as relapse leads to the death of these patients. While the advance of preclinical models has been essential to understand GBM biology and evolution, the models for GBM relapse are scarce, thereby delaying translational studies.

Methods: A CRISPR/Cas9-Cre hybrid system was used for modeling primary glioblastoma. Radiance values were used for defining tumors amenable for treatment. Fluorescent-guided surgery, chemotherapy or radiotherapy were administered. Recurrent tumors were assessed by histopathology.

Results: After surgical resection, complete response to treatment was achieved and tumor regrowth was evidenced in all subjects. EGFRviii amplification model did not respond to the chemo- and radiation therapy regimen used. On the contrary, NF1 deletion model responded to all treatment modalities.

Conclusion: Fluorescence guided surgical debulking is feasible and results in recurrent GBM. Histopathological assessment shows diversification of patterns in the relapsed tumor.