title: Molecular targeting of glioblastoma: Drug discovery and therapies.
abstract: Despite advances in treatment for glioblastoma multiforme (GBM), patient prognosis remains poor. Although there is growing evidence that molecular targeting could translate into better survival for GBM, current clinical data show limited impact on survival. Recent progress in GBM genomics implicate several activated pathways and numerous mutated genes. This molecular diversity can partially explain therapeutic resistance and several approaches have been postulated to target molecular changes. Furthermore, most drugs are unable to reach effective concentrations within the tumor owing to elevated intratumoral pressure, restrictive vasculature and other limiting factors. Here, we describe the preclinical and clinical developments in treatment strategies of GBM. We review the current clinical trials for GBM and discuss the challenges and future directions of targeted therapies.
authors.affiliation: Departments of Neurosurgery, Johns Hopkins University School of Medicine, CRB II Rm. 257, 1550 Orleans Street, Baltimore, MD 21231, USA.
authors.forename: Ren-Yuan
authors.initials: RY
authors.lastname: Bai
authors.affiliation: Departments of Neurosurgery, Johns Hopkins University School of Medicine, CRB II Rm. 257, 1550 Orleans Street, Baltimore, MD 21231, USA.
authors.forename: Verena
authors.initials: V
authors.lastname: Staedtke
authors.affiliation: Departments of Neurosurgery, Johns Hopkins University School of Medicine, CRB II Rm. 257, 1550 Orleans Street, Baltimore, MD 21231, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riggins
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D055808:Drug Discovery / Q000379:methods*; D004341:Drug Evaluation; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D023281:Genomics / Q000379:methods*; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D006801:Humans; D051379:Mice; D008954:Models, Biological; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor