title: Targeting integrins in malignant glioma.
abstract: The integrin family of cell adhesion receptors is emerging as a promising target of anticancer therapy. AlphaVbeta3 and alphaVbeta5 integrins are overexpressed on both glioma cells and tumor vasculature. Cilengitide, the most advanced specific integrin inhibitor in oncology, has shown antitumor activity against glioma in early clinical trials. Durable remissions have been observed in phase I and phase II trials for recurrent glioblastoma (GBM) with both lower and higher doses of cilengitide. Pilot trials in newly diagnosed glioblastoma in conjunction with standard chemoradiotherapy have been encouraging. Preclinical data suggest synergy with concomitant chemo- and radiation therapy. A pivotal phase III study (CENTRIC) in newly diagnosed GBM patients is currently recruiting. This paper summarizes the current understanding of the role of integrins and their inhibition in gliomagenesis. The background and design of ongoing trials are outlined.
authors.affiliation: Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland. ghazaleh.tabatabai@usz.ch
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Tabatabai
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.forename: Burt
authors.initials: B
authors.lastname: Nabors
authors.forename: Martin
authors.initials: M
authors.lastname: Picard
authors.forename: David
authors.initials: D
authors.lastname: Reardon
authors.forename: Tom
authors.initials: T
authors.lastname: Mikkelsen
authors.forename: Curzio
authors.initials: C
authors.lastname: Ruegg
authors.forename: Roger
authors.initials: R
authors.lastname: Stupp
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D016023:Integrins
references.citation: Clin Cancer Res. 2005 Sep 1;11(17):6270-9
references.pmid: 16144931
references.citation: Genome Biol. 2007;8(5):215
references.pmid: 17543136
references.citation: Cell Stem Cell. 2010 May 7;6(5):421-32
references.pmid: 20452317
references.citation: Cancer Res. 2009 Apr 15;69(8):3308-16
references.pmid: 19351861
references.citation: J Cell Sci. 2006 Dec 1;119(Pt 23):4803-10
references.pmid: 17130294
references.citation: Nat Rev Cancer. 2008 Aug;8(8):604-17
references.pmid: 18497750
references.citation: Recent Results Cancer Res. 2010;180:83-101
references.pmid: 20033379
references.citation: Science. 2002 Apr 5;296(5565):151-5
references.pmid: 11884718
references.citation: Cell Mol Life Sci. 2003 Jun;60(6):1135-57
references.pmid: 12861381
references.citation: J Clin Oncol. 2007 May 1;25(13):1651-7
references.pmid: 17470857
references.citation: Rev Recent Clin Trials. 2007 Sep;2(3):163-8
references.pmid: 18474001
references.citation: Brain Pathol. 2008 Jul;18(3):378-86
references.pmid: 18394009
references.citation: Cancer Metastasis Rev. 2007 Jun;26(2):333-9
references.pmid: 17458506
references.citation: J Clin Oncol. 2010 Jun 1;28(16):2712-8
references.pmid: 20439646
references.citation: J Clin Oncol. 2008 Dec 1;26(34):5610-7
references.pmid: 18981465
references.citation: Neuro Oncol. 2009 Dec;11(6):747-56
references.pmid: 19221171
references.citation: Science. 2003 May 16;300(5622):1155-9
references.pmid: 12750523
references.citation: N Engl J Med. 2005 Mar 10;352(10):997-1003
references.pmid: 15758010
references.citation: J Clin Oncol. 2008 Feb 20;26(6):919-24
references.pmid: 18281665
references.citation: Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1536-43
references.pmid: 16863930
references.citation: Clin Cancer Res. 2006 Jul 1;12(13):3942-9
references.pmid: 16818691
references.citation: Angiogenesis. 2003;6(2):105-19
references.pmid: 14739617
references.citation: Oncogene. 2005 Aug 18;24(35):5414-22
references.pmid: 15940265
references.citation: Cancer Res. 2001 Mar 15;61(6):2744-50
references.pmid: 11289157
references.citation: Lancet Oncol. 2009 May;10(5):459-66
references.pmid: 19269895
references.citation: Nat Med. 2009 Jul;15(7):726; author reply 727
references.pmid: 19584855
references.citation: J Neurosurg. 2001 Jun;94(6):978-84
references.pmid: 11409528
references.citation: Hematol Oncol Clin North Am. 2004 Oct;18(5):1039-57, viii
references.pmid: 15474334
references.citation: Cancer Cell. 2009 Mar 3;15(3):220-31
references.pmid: 19249680
references.citation: J Cell Sci. 1995 Aug;108 ( Pt 8):2825-38
references.pmid: 7593323
references.citation: Int J Cancer. 2009 Jun 1;124(11):2719-27
references.pmid: 19199360
references.citation: PLoS One. 2010 Jun 11;5(6):e11084
references.pmid: 20552031
references.citation: Neurosurgery. 2001 Aug;49(2):380-9; discussion 390
references.pmid: 11504114
references.citation: Cancer Res. 2007 Oct 15;67(20):9921-8
references.pmid: 17942924
references.citation: Neurosurgery. 2001 Jan;48(1):151-7
references.pmid: 11152340
references.citation: J Med Chem. 2002 Feb 28;45(5):1045-51
references.pmid: 11855984
references.citation: Int J Cancer. 2002 Apr 10;98(5):690-7
references.pmid: 11920637
references.citation: Endothelium. 2006 Mar-Apr;13(2):113-35
references.pmid: 16728329
references.citation: Nat Rev Cancer. 2010 Jan;10(1):9-22
references.pmid: 20029421
references.citation: Drug Resist Updat. 2010 Feb-Apr;13(1-2):16-28
references.pmid: 20061178
references.citation: J Clin Oncol. 2007 May 1;25(13):1637-8
references.pmid: 17470853
references.citation: Eur J Cancer. 2003 May;39(7):917-26
references.pmid: 12706360
references.citation: Nat Med. 2009 Apr;15(4):392-400
references.pmid: 19305413
references.citation: N Engl J Med. 2005 Mar 10;352(10):987-96
references.pmid: 15758009
references.citation: Cancer Res. 2008 Sep 15;68(18):7323-31
references.pmid: 18794119