title: Targeting core (mutated) pathways of high-grade gliomas: challenges of intrinsic resistance and drug efflux.
abstract: High-grade gliomas are the most common type of primary brain tumor and are among the most lethal types of human cancer. Most patients with a high-grade glioma have glioblastoma multiforme (GBM), the most malignant glioma subtype that is associated with a very aggressive disease course and short overall survival. Standard treatment of newly diagnosed GBM involves surgery followed by chemoradiation with temozolomide. However, despite this extensive treatment the mean overall survival is still only 14.6 months and more effective treatments are urgently needed. Although different types of GBMs are indistinguishable by histopathology, novel molecular pathological techniques allow discrimination between the four main GBM subtypes. Targeting the aberrations in the molecular pathways underlying these subtypes is a promising strategy to improve therapy. In this article, we will discuss the potential avenues and pitfalls of molecularly targeted therapies for the treatment of GBM.
authors: Department of Clinical Chemistry/Preclinical Pharmacology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors: Fan
authors: F
authors: Lin
authors: Mark C
authors: MC
authors: de Gooijer
authors: Diana
authors: D
authors: Hanekamp
authors: Dieta
authors: D
authors: Brandsma
authors: Jos H
authors: JH
authors: Beijnen
authors: Olaf
authors: O
authors: van Tellingen
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents