title: Glioblastoma.
abstract: Glioblastoma is the most common and aggressive primary brain tumor in adults. Defining histopathologic features are necrosis and endothelial proliferation, resulting in the assignment of grade IV, the highest grade in the World Health Organization (WHO) classification of brain tumors. The classic clinical term "secondary glioblastoma" refers to a minority of glioblastomas that evolve from previously diagnosed WHO grade II or grade III gliomas. Specific point mutations of the genes encoding isocitrate dehydrogenase (IDH) 1 or 2 appear to define molecularly these tumors that are associated with younger age and more favorable outcome; the vast majority of glioblastomas are IDH wild-type. Typical molecular changes in glioblastoma include mutations in genes regulating receptor tyrosine kinase (RTK)/rat sarcoma (RAS)/phosphoinositide 3-kinase (PI3K), p53, and retinoblastoma protein (RB) signaling. Standard treatment of glioblastoma includes surgery, radiotherapy, and alkylating chemotherapy. Promoter methylation of the gene encoding the DNA repair protein, O(6)-methylguanyl DNA methyltransferase (MGMT), predicts benefit from alkylating chemotherapy with temozolomide and guides choice of first-line treatment in elderly patients. Current developments focus on targeting the molecular characteristics that drive the malignant phenotype, including altered signal transduction and angiogenesis, and more recently, various approaches of immunotherapy.
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland. Electronic address: hans-georg.wirsching@usz.ch.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Wirsching
authors.affiliation: Departments of Oncology and Molecular Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Evanthia
authors.initials: E
authors.lastname: Galanis
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005909:Glioblastoma / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D059906:Neuroimaging; D057089:Pathology, Molecular; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: angiogenesis; glioblastoma; glioma-initiating cell; immunotherapy; molecular subtype; radiotherapy; temozolomide