title: Glioma Subclassifications and Their Clinical Significance.
abstract: The impact of targeted therapies in glioma has been modest. All the therapies that have demonstrated a significant survival benefit for gliomas in Phase III trials, including radiation, chemotherapy (temozolomide and PCV [procarbazine, lomustine, vincristine]), and tumor-treating fields, are based on nonspecific targeting of proliferating cells. Recent advances in the molecular understanding of gliomas suggest some potential reasons for the failure of more targeted therapies in gliomas. Specifically, the histologic-based glioma classification is composed of multiple different molecular subtypes with distinct biology, natural history, and prognosis. As a result of these insights, the diagnosis and classification of gliomas have recently been updated by the World Health Organization. However, these changes and other novel observations regarding glioma biomarkers and subtypes highlight several clinical challenges. First, the field is faced with the difficulty of reinterpreting the results of prior studies and retrospective data using the new classifications to clarify prognostic assessments and treatment recommendations for patients. Second, the new classifications and insights require rethinking the design and stratification of future clinical trials. Last, these observations provide the essential framework for the development and testing of new specific targeted therapies for particular glioma subtypes. This review aims to summarize the current literature regarding glioma subclassifications and their clinical relevance in this evolving field.
authors.affiliation: Department of Neurology, Clinical Neurosciences Center, University of Utah, Salt Lake City, UT, USA.
authors.forename: Ricky
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Neurology, Clinical Neurosciences Center, University of Utah, Salt Lake City, UT, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Smith-Cohn
authors.affiliation: Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Cohen
authors.affiliation: Department of Neurosurgery, Huntsman Cancer Institute and Clinical Neuroscience Center, University of Utah, Salt Lake City, UT, USA. howard.colman@hci.utah.edu.
authors.forename: Howard
authors.initials: H
authors.lastname: Colman
mesh_terms: D001932:Brain Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D017353:Gene Deletion; D015870:Gene Expression; D005910:Glioma / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D014944:World Health Organization
keywords: 1p/19q co-deletion; 2HG; BRAF; EGFR; Ependymoma; Glioma; IDH mutation; MGMT methylation; MR spectroscopy; TERT promoter; Targeted therapy; Vaccine therapy