Mouse Models of Glioblastoma

ABSTRACT

Glioblastoma is one of the most common malignant brain tumors. The prognosis for glioblastoma is still very poor despite intensive treatment by surgery, radiation, and chemotherapy. To develop new therapies for glioblastoma, preclinical mouse models are essential for analyzing the biology of glioblastoma, identifying new therapeutic targets, and evaluating the potential of new therapeutic strategies. Current preclinical glioblastoma models are classified into two categories: xenografts and genetically engineered mouse models. Xenografts are classified into two categories: glioblastoma cell-line xenografts and patient-derived xenografts. Glioblastoma cell-line xenografts generally have the advantages of high engraftment and growth rates, but it is doubtful whether glioblastoma cell-line xenografts reflect the true biological nature of glioblastoma. Patient-derived xenografts retain both the genetic and histological features of the primary tumor, and thus are expected to be good preclinical models in translational glioblastoma research. However, they cannot fully reflect the host’s antitumor immunity in human glioblastoma. Glioblastoma genetically engineered mouse models make it possible to pinpoint genetic alterations involved in tumor initiation and progression, but tumors are usually composed of cells with specific, homogeneous genetic changes, and thus cannot completely reflect the intratumoral genomic and phenotypic heterogeneity of glioblastoma. Presently, patient-derived xenografts and genetically engineered mouse models are excellent glioblastoma mouse models for current use, but more work is needed to establish mouse models that fully recapitulate human glioblastoma.