title: Contemporary murine models in preclinical astrocytoma drug development.
abstract: Despite 6 decades of research, only 3 drugs have been approved for astrocytomas, the most common malignant primary brain tumors. However, clinical drug development is accelerating with the transition from empirical, cytotoxic therapy to precision, targeted medicine. Preclinical animal model studies are critical for prioritizing drug candidates for clinical development and, ultimately, for their regulatory approval. For decades, only murine models with established tumor cell lines were available for such studies. However, these poorly represent the genomic and biological properties of human astrocytomas, and their preclinical use fails to accurately predict efficacy in clinical trials. Newer models developed over the last 2 decades, including patient-derived xenografts, genetically engineered mice, and genetically engineered cells purified from human brains, more faithfully phenocopy the genomics and biology of human astrocytomas. Harnessing the unique benefits of these models will be required to identify drug targets, define combination therapies that circumvent inherent and acquired resistance mechanisms, and develop molecular biomarkers predictive of drug response and resistance. With increasing recognition of the molecular heterogeneity of astrocytomas, employing multiple, contemporary models in preclinical drug studies promises to increase the efficiency of drug development for specific, molecularly defined subsets of tumors.
authors.affiliation: Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina (R.S.M., M.V., C.R.M.); Departments of Neurosurgery and Neurology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (J.W.); Department of Neurology, Lineberger Comprehensive Cancer Center, and Neurosciences Center University of North Carolina School of Medicine, Chapel Hill, North Carolina (C.R.M.).
authors.forename: Robert S
authors.initials: RS
authors.lastname: McNeill
authors.affiliation: Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina (R.S.M., M.V., C.R.M.); Departments of Neurosurgery and Neurology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (J.W.); Department of Neurology, Lineberger Comprehensive Cancer Center, and Neurosciences Center University of North Carolina School of Medicine, Chapel Hill, North Carolina (C.R.M.).
authors.forename: Mark
authors.initials: M
authors.lastname: Vitucci
authors.affiliation: Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina (R.S.M., M.V., C.R.M.); Departments of Neurosurgery and Neurology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (J.W.); Department of Neurology, Lineberger Comprehensive Cancer Center, and Neurosciences Center University of North Carolina School of Medicine, Chapel Hill, North Carolina (C.R.M.).
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina (R.S.M., M.V., C.R.M.); Departments of Neurosurgery and Neurology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (J.W.); Department of Neurology, Lineberger Comprehensive Cancer Center, and Neurosciences Center University of North Carolina School of Medicine, Chapel Hill, North Carolina (C.R.M.).
authors.forename: C Ryan
authors.initials: CR
authors.lastname: Miller
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy* / Q000235:genetics*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D055808:Drug Discovery; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D051379:Mice
chemical_list: D000970:Antineoplastic Agents
keywords: astrocytoma; drug development; genomics; glioblastoma; mouse models