title: Vascular endothelial growth factor inhibitors in malignant gliomas.
abstract: Glioblastomas are highly vascularized tumors. Treatment strategies targeting angiogenesis have demonstrated promising results in preclinical studies and clinical trials in patients with malignant gliomas. Anti-VEGF agents, either alone or in combination with chemotherapy, have been associated with reduction in vasogenic brain edema, and prolonged progression-free survival. Larger prospective clinical trials are needed to validate these results, and to assess the impact of these agents on overall survival. Unfortunately, antiangiogenic treatment inevitably fails in most patients. Further studies are needed to understand the molecular pathways that enable a tumor to evade antiangiogenic therapy.
authors.affiliation: Stephen E. and Catherine Pappas Center for Neuro-Oncology, Department of Neurology, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center, Boston, MA, USA. pbrastianos@partners.org
authors.forename: Priscilla K
authors.initials: PK
authors.lastname: Brastianos
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Batchelor
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000098:blood supply*; D002986:Clinical Trials as Topic; D005910:Glioma / Q000098:blood supply*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D015398:Signal Transduction; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D042442:Vascular Endothelial Growth Factors
references.citation: Neurosurgery. 2004 Aug;55(2):426-32; discussion 432
references.pmid: 15271251
references.citation: J Clin Oncol. 2009 May 20;27(15):2542-52
references.pmid: 19332720
references.citation: Nature. 1994 Feb 10;367(6463):576-9
references.pmid: 8107827
references.citation: Cancer Res. 2001 Aug 15;61(16):6020-4
references.pmid: 11507045
references.citation: Nat Rev Cancer. 2007 Jun;7(6):475-85
references.pmid: 17522716
references.citation: Nat Rev Drug Discov. 2007 Apr;6(4):273-86
references.pmid: 17396134
references.citation: Science. 1999 Jun 18;284(5422):1994-8
references.pmid: 10373119
references.citation: Clin Cancer Res. 2007 Feb 15;13(4):1253-9
references.pmid: 17317837
references.citation: Neuro Oncol. 2008 Jun;10(3):355-60
references.pmid: 18436627
references.citation: N Engl J Med. 2008 Jul 24;359(4):378-90
references.pmid: 18650514
references.citation: J Clin Oncol. 2009 Oct 1;27(28):4733-40
references.pmid: 19720927
references.citation: Cancer Res. 1996 Sep 15;56(18):4264-6
references.pmid: 8797602
references.citation: J Clin Oncol. 2007 Oct 20;25(30):4722-9
references.pmid: 17947719
references.citation: J Nucl Med. 2006 Mar;47(3):393-403
references.pmid: 16513607
references.citation: Cancer Res. 1995 Dec 15;55(24):6161-5
references.pmid: 8521408
references.citation: Cancer Res. 1994 Sep 1;54(17):4564-8
references.pmid: 8062241
references.citation: Science. 1997 Jul 4;277(5322):48-50
references.pmid: 9229772
references.citation: Oncogene. 1997 May 1;14(17):2005-13
references.pmid: 9160879
references.citation: J Magn Reson Imaging. 2007 Aug;26(2):235-49
references.pmid: 17623889
references.citation: Int J Radiat Oncol Biol Phys. 1994 Jun 15;29(3):427-31
references.pmid: 8005794
references.citation: Cancer Treat Res. 2004;117:169-90
references.pmid: 15015561
references.citation: Neuro Oncol. 2005 Oct;7(4):436-51
references.pmid: 16212809
references.citation: Cancer Res. 2002 Jul 15;62(14):4015-22
references.pmid: 12124335
references.citation: Int J Radiat Oncol Biol Phys. 2010 Sep 1;78(1):85-90
references.pmid: 20137866
references.citation: Cancer Cell. 2004 Dec;6(6):553-63
references.pmid: 15607960
references.citation: J Clin Oncol. 2010 Jun 10;28(17):2817-23
references.pmid: 20458050
references.citation: Lancet. 2006 Oct 14;368(9544):1329-38
references.pmid: 17046465
references.citation: Invest New Drugs. 2015 Feb;33(1):247-53
references.pmid: 25388940
references.citation: J Clin Oncol. 2007 Oct 20;25(30):4714-21
references.pmid: 17947718
references.citation: Cancer Res. 2006 Dec 15;66(24):11851-8
references.pmid: 17178882
references.citation: Methods Mol Biol. 2009;472:323-42
references.pmid: 19107440
references.citation: Nat Med. 2001 Sep;7(9):987-9
references.pmid: 11533692
references.citation: Cancer Cell. 2007 Jan;11(1):83-95
references.pmid: 17222792
references.citation: J Clin Oncol. 1990 Jul;8(7):1277-80
references.pmid: 2358840
references.citation: Science. 2005 Jan 7;307(5706):58-62
references.pmid: 15637262
references.citation: Cancer Cell. 2007 Jan;11(1):69-82
references.pmid: 17222791
references.citation: Nat Rev Cancer. 2008 Aug;8(8):592-603
references.pmid: 18650835
references.citation: Cancer Cell. 2004 Nov;6(5):507-16
references.pmid: 15542434
references.citation: Rev Neurol (Paris). 2008 Jun-Jul;164(6-7):588-94
references.pmid: 18565358
references.citation: Int J Cancer. 1999 Feb 19;84(1):10-8
references.pmid: 9988225
references.citation: Clin Cancer Res. 2005 Nov 15;11(22):8145-57
references.pmid: 16299247
references.citation: Cancer Res. 2006 Aug 15;66(16):7843-8
references.pmid: 16912155
references.citation: J Neuropathol Exp Neurol. 2006 Jun;65(6):529-39
references.pmid: 16783163
references.citation: J Pharmacol Exp Ther. 2006 Dec;319(3):1070-80
references.pmid: 16959960
references.citation: N Engl J Med. 2007 Jan 11;356(2):115-24
references.pmid: 17215529
references.citation: Int J Radiat Oncol Biol Phys. 2007 Apr 1;67(5):1526-37
references.pmid: 17234361
references.citation: Nat Rev Cancer. 2006 Jul;6(7):521-34
references.pmid: 16794635
references.citation: J Clin Oncol. 2006 Jul 10;24(20):3293-8
references.pmid: 16829653
references.citation: Cancer Res. 2004 Jun 1;64(11):3731-6
references.pmid: 15172975
references.citation: Nature. 2006 Dec 21;444(7122):1083-7
references.pmid: 17183323
references.citation: Nature. 2000 Sep 14;407(6801):242-8
references.pmid: 11001067
references.citation: Nature. 2006 Dec 21;444(7122):1032-7
references.pmid: 17183313
references.citation: Nat Rev Neurosci. 2007 Aug;8(8):610-22
references.pmid: 17643088
references.citation: Cancer Res. 2007 Mar 15;67(6):2729-35
references.pmid: 17363594
references.citation: Cancer. 2010 Apr 1;116(7):1776-82
references.pmid: 20143438
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11393-8
references.pmid: 12177445
references.citation: N Engl J Med. 2008 May 8;358(19):2039-49
references.pmid: 18463380
references.citation: Cancer Res. 2000 Sep 1;60(17):4959-67
references.pmid: 10987313
references.citation: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references.pmid: 10655437
references.citation: Neurology. 2008 Mar 4;70(10):779-87
references.pmid: 18316689
references.citation: J Clin Oncol. 2009 Jun 20;27(18):2905-8
references.pmid: 19451418
references.citation: Lab Invest. 2000 Jun;80(6):837-49
references.pmid: 10879735
references.citation: Nature. 1992 Oct 29;359(6398):845-8
references.pmid: 1279432
references.citation: Neurology. 2006 Apr 25;66(8):1258-60
references.pmid: 16636248
references.citation: N Engl J Med. 2007 Jan 11;356(2):125-34
references.pmid: 17215530
references.citation: Cancer Res. 1991 Oct 15;51(20):5760-5
references.pmid: 1717153
references.citation: J Clin Oncol. 2010 Apr 10;28(11):1963-72
references.pmid: 20231676
references.citation: Mol Biol Cell. 1993 Jan;4(1):121-33
references.pmid: 7680247
references.citation: Br J Cancer. 2001 Dec 14;85(12):2010-6
references.pmid: 11747347
references.citation: Nat Med. 1997 Feb;3(2):177-82
references.pmid: 9018236
references.citation: J Clin Oncol. 2010 Apr 20;28(12):e188-9; author reply e190-2
references.pmid: 20159801
references.citation: J Neurooncol. 2006 Jul;78(3):281-93
references.pmid: 16554966
references.citation: Exp Cell Res. 2006 Mar 10;312(5):549-60
references.pmid: 16336962
references.citation: Blood. 2006 Apr 1;107(7):2774-6
references.pmid: 16339405
references.citation: Acta Neuropathol. 2005 Jan;109(1):93-108
references.pmid: 15685439