title: Molecular neuro-oncology and the challenge of the blood-brain barrier.
abstract: Despite epochal advances in brain imaging, radiation delivery, and neurosurgical sophistication, the survival of patients with primary malignant astrocytomas has not been met with commensurate progress. While temozolomide, an alkylating agent, has demonstrated a survival benefit, median survival in the past decade of patients with glioblastoma (GBM) remains an obdurate 15 months and add-on therapies have not significantly prolonged life. It is likely that further advances may need to await additional discoveries that are slowly being revealed by molecular exploration of the tumor genome. This review summarizes many recent developments in molecular neuro-oncology and examines formidable challenges imposed by the highly restrictive properties of the blood-brain barrier (BBB) that impact effective drug delivery.
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL; Coleman Foundation Comprehensive Brain Tumor Center, Rush University Medical Center, Chicago, IL. Electronic address: robert_aiken@rush.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Aiken
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002872:Chromosome Deletion; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D007521:Isocitrate Dehydrogenase; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D045643:DNA Repair Enzymes; D000077204:Temozolomide