title: Heparin in malignant glioma: review of preclinical studies and clinical results.
abstract: Glioblastoma multiforme (GBM) is the most common primary brain tumor that is invariably lethal. Novel treatments are desperately needed. In various cancers, heparin and its low molecular weight derivatives (LMWHs), commonly used for the prevention and treatment of thrombosis, have shown therapeutic potential. Here we systematically review preclinical and clinical studies of heparin and LMWHs as anti-tumor agents in GBM. Even though the number of studies is limited, there is suggestive evidence that heparin may have various effects on GBM. These effects include the inhibition of tumor growth and angiogenesis in vitro and in vivo, and the blocking of uptake of extracellular vesicles. However, heparin can also block the uptake of (potential) anti-tumor agents. Clinical studies suggest a non-significant trend of prolonged survival of LMWH treated GBM patients, with some evidence of increased major bleedings. Heparin mimetics lacking anticoagulant effect are therefore a potential alternative to heparin/LMWH and are discussed as well.
authors.affiliation: Department of Neurosurgery, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.|Brain Center Rudolf Magnus, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Rosalie
authors.initials: R
authors.lastname: Schnoor
authors.affiliation: Department of Neurosurgery, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.|Brain Center Rudolf Magnus, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Sybren L N
authors.initials: SL
authors.lastname: Maas
authors.affiliation: Department of Neurosurgery, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. M.L.D.Broekman-4@umcutrecht.nl.|Brain Center Rudolf Magnus, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. M.L.D.Broekman-4@umcutrecht.nl.
authors.forename: Marike L D
authors.initials: ML
authors.lastname: Broekman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D005910:Glioma / Q000188:drug therapy*; D006493:Heparin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D006493:Heparin
keywords: Glioblastoma multiforme; Glioma; Heparin; Low molecular weight heparin