title: Emerging therapies for glioblastoma.
abstract: OBJECTIVE
  Glioblastoma is the most common primary malignant brain tumor, but despite multimodal treatment with surgery, radiotherapy, and temozolomide chemotherapy, the prognosis is poor, with a median survival of 16 to 19 months and poor quality of life throughout the disease course. New treatments are needed.
  
  
  METHODS
  Articles were identified through a search of PubMed references from March 2005 through January 2014, using the terms glioblastoma, glioma, malignant glioma, and brain neoplasm, as well as by search of the authors' files. Clinical trials were identified in the Clinicaltrials.gov registry.
  
  
  RESULTS
  Advances in the understanding of the molecular biology of glioblastoma are being rapidly translated into innovative clinical trials, capitalizing on improved genomic, epigenetic, transcriptional, and proteomic characterization of glioblastomas as well as host factors, including the brain microenvironment and immune system interactions. Therapies targeting tumor growth factor receptors and downstream pathways, angiogenesis, modulation of cancer stemlike cells, cell cycle regulation, oncolytic viruses, new radiotherapy techniques, and immunotherapy, including vaccines and modulation of immune checkpoints (eg, programmed cell death 1 and cytotoxic T-lymphocyte antigen 4), are under investigation. In addition to novel agents, techniques to circumvent the blood-brain barrier to facilitate central nervous system drug exposure are being developed.
  
  
  CONCLUSIONS
  Glioblastoma is an aggressive tumor with heterogeneous molecular features and complex host interactions, many of which are amenable to therapeutic intervention. Meaningful treatment advances will depend on identifying agents that target mechanistic vulnerabilities that are relevant to specific subgroups of patients; increasing patient enrollment into clinical trials is essential to accelerate the development of patient-tailored treatments.
authors.affiliation: Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Alissa A
authors.initials: AA
authors.lastname: Thomas
authors.affiliation: Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Cameron W
authors.initials: CW
authors.lastname: Brennan
authors.affiliation: Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: DeAngelis
authors.affiliation: Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Omuro
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000628:therapy*; D064987:Cell- and Tissue-Based Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D000077204:Temozolomide
chemical_list: D003606:Dacarbazine; D000077204:Temozolomide