Skip to main content
Erschienen in: Targeted Oncology 3/2010

01.09.2010 | Review

Targeting integrins in malignant glioma

verfasst von: Ghazaleh Tabatabai, Michael Weller, Burt Nabors, Martin Picard, David Reardon, Tom Mikkelsen, Curzio Ruegg, Roger Stupp

Erschienen in: Targeted Oncology | Ausgabe 3/2010

Einloggen, um Zugang zu erhalten

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.
Literatur
3.
Zurück zum Zitat Ruegg C, Mariotti A (2003) Vascular integrins: pleiotropic adhesion and signaling molecules in vascular homeostasis and angiogenesis. Cell Mol Life Sci 60(6):1135–1157PubMed Ruegg C, Mariotti A (2003) Vascular integrins: pleiotropic adhesion and signaling molecules in vascular homeostasis and angiogenesis. Cell Mol Life Sci 60(6):1135–1157PubMed
5.
Zurück zum Zitat Alghisi GC, Ruegg C (2006) Vascular integrins in tumor angiogenesis: mediators and therapeutic targets. Endothelium 13(2):113–135CrossRefPubMed Alghisi GC, Ruegg C (2006) Vascular integrins in tumor angiogenesis: mediators and therapeutic targets. Endothelium 13(2):113–135CrossRefPubMed
6.
Zurück zum Zitat Schnell O, Krebs B, Wagner E, Romagna A, Beer AJ, Grau SJ, Thon N, Goetz C, Kretzschmar HA, Tonn JC, Goldbrunner RH (2008) Expression of integrin alphavbeta3 in gliomas correlates with tumor grade and is not restricted to tumor vasculature. Brain Pathol 18(3):378–386. doi:10.1111/j.1750-3639.2008.00137.x CrossRefPubMed Schnell O, Krebs B, Wagner E, Romagna A, Beer AJ, Grau SJ, Thon N, Goetz C, Kretzschmar HA, Tonn JC, Goldbrunner RH (2008) Expression of integrin alphavbeta3 in gliomas correlates with tumor grade and is not restricted to tumor vasculature. Brain Pathol 18(3):378–386. doi:10.​1111/​j.​1750-3639.​2008.​00137.​x CrossRefPubMed
7.
Zurück zum Zitat Taga T, Suzuki A, Gonzalez-Gomez I, Gilles FH, Stins M, Shimada H, Barsky L, Weinberg KI, Laug WE (2002) Alpha v-integrin antagonist emd 121974 induces apoptosis in brain tumor cells growing on vitronectin and tenascin. Int J Cancer 98(5):690–697. doi:10.1002/ijc.10265 CrossRefPubMed Taga T, Suzuki A, Gonzalez-Gomez I, Gilles FH, Stins M, Shimada H, Barsky L, Weinberg KI, Laug WE (2002) Alpha v-integrin antagonist emd 121974 induces apoptosis in brain tumor cells growing on vitronectin and tenascin. Int J Cancer 98(5):690–697. doi:10.​1002/​ijc.​10265 CrossRefPubMed
8.
Zurück zum Zitat Bello L, Francolini M, Marthyn P, Zhang J, Carroll RS, Nikas DC, Strasser JF, Villani R, Cheresh DA, Black PM (2001) Alpha(v)beta3 and alpha(v)beta5 integrin expression in glioma periphery. Neurosurgery 49(2):380–389, discussion 390CrossRefPubMed Bello L, Francolini M, Marthyn P, Zhang J, Carroll RS, Nikas DC, Strasser JF, Villani R, Cheresh DA, Black PM (2001) Alpha(v)beta3 and alpha(v)beta5 integrin expression in glioma periphery. Neurosurgery 49(2):380–389, discussion 390CrossRefPubMed
9.
Zurück zum Zitat Beer AJ, Haubner R, Sarbia M, Goebel M, Luderschmidt S, Grosu AL, Schnell O, Niemeyer M, Kessler H, Wester HJ, Weber WA, Schwaiger M (2006) Positron emission tomography using [18f]galacto-rgd identifies the level of integrin alpha(v)beta3 expression in man. Clin Cancer Res 12(13):3942–3949. doi:10.1158/1078-0432.CCR-06-0266 CrossRefPubMed Beer AJ, Haubner R, Sarbia M, Goebel M, Luderschmidt S, Grosu AL, Schnell O, Niemeyer M, Kessler H, Wester HJ, Weber WA, Schwaiger M (2006) Positron emission tomography using [18f]galacto-rgd identifies the level of integrin alpha(v)beta3 expression in man. Clin Cancer Res 12(13):3942–3949. doi:10.​1158/​1078-0432.​CCR-06-0266 CrossRefPubMed
11.
Zurück zum Zitat Maurer GD, Tritschler I, Adams B, Tabatabai G, Wick W, Stupp R, Weller M (2009) Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro. Neuro Oncol 11(6):747–756. doi:10.1215/15228517-2009-012 CrossRefPubMed Maurer GD, Tritschler I, Adams B, Tabatabai G, Wick W, Stupp R, Weller M (2009) Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro. Neuro Oncol 11(6):747–756. doi:10.​1215/​15228517-2009-012 CrossRefPubMed
12.
16.
Zurück zum Zitat Nieder C, Wiedenmann N, Andratschke NH, Astner ST, Molls M (2007) Radiation therapy plus angiogenesis inhibition with bevacizumab: rationale and initial experience. Rev Recent Clin Trials 2(3):163–168CrossRefPubMed Nieder C, Wiedenmann N, Andratschke NH, Astner ST, Molls M (2007) Radiation therapy plus angiogenesis inhibition with bevacizumab: rationale and initial experience. Rev Recent Clin Trials 2(3):163–168CrossRefPubMed
19.
Zurück zum Zitat Albert JM, Cao C, Geng L, Leavitt L, Hallahan DE, Lu B (2006) Integrin alpha v beta 3 antagonist cilengitide enhances efficacy of radiotherapy in endothelial cell and non-small-cell lung cancer models. Int J Radiat Oncol Biol Phys 65(5):1536–1543. doi:10.1016/j.ijrobp.2006.04.036 PubMed Albert JM, Cao C, Geng L, Leavitt L, Hallahan DE, Lu B (2006) Integrin alpha v beta 3 antagonist cilengitide enhances efficacy of radiotherapy in endothelial cell and non-small-cell lung cancer models. Int J Radiat Oncol Biol Phys 65(5):1536–1543. doi:10.​1016/​j.​ijrobp.​2006.​04.​036 PubMed
21.
Zurück zum Zitat Wild-Bode C, Weller M, Rimner A, Dichgans J, Wick W (2001) Sublethal irradiation promotes migration and invasiveness of glioma cells: implications for radiotherapy of human glioblastoma. Cancer Res 61(6):2744–2750PubMed Wild-Bode C, Weller M, Rimner A, Dichgans J, Wick W (2001) Sublethal irradiation promotes migration and invasiveness of glioma cells: implications for radiotherapy of human glioblastoma. Cancer Res 61(6):2744–2750PubMed
22.
Zurück zum Zitat Mikkelsen T, Brodie C, Finniss S, Berens ME, Rennert JL, Nelson K, Lemke N, Brown SL, Hahn D, Neuteboom B, Goodman SL (2009) Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule-dependency. Int J Cancer 124(11):2719–2727. doi:10.1002/ijc.24240 CrossRefPubMed Mikkelsen T, Brodie C, Finniss S, Berens ME, Rennert JL, Nelson K, Lemke N, Brown SL, Hahn D, Neuteboom B, Goodman SL (2009) Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule-dependency. Int J Cancer 124(11):2719–2727. doi:10.​1002/​ijc.​24240 CrossRefPubMed
23.
Zurück zum Zitat Reynolds AR, Hart IR, Watson AR, Welti JC, Silva RG, Robinson SD, Da Violante G, Gourlaouen M, Salih M, Jones MC, Jones DT, Saunders G, Kostourou V, Perron-Sierra F, Norman JC, Tucker GC, Hodivala-Dilke KM (2009) Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors. Nat Med 15(4):392–400. doi:10.1038/nm.1941 CrossRefPubMed Reynolds AR, Hart IR, Watson AR, Welti JC, Silva RG, Robinson SD, Da Violante G, Gourlaouen M, Salih M, Jones MC, Jones DT, Saunders G, Kostourou V, Perron-Sierra F, Norman JC, Tucker GC, Hodivala-Dilke KM (2009) Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors. Nat Med 15(4):392–400. doi:10.​1038/​nm.​1941 CrossRefPubMed
25.
Zurück zum Zitat Nabors B, Mikkelsen T, Rosenfeld S, Hochberg F, Shastry Akella N, Fisher J, Cloud G, Zhang Y, Carson K, Wittemer S, Colvevas D, Grossman S, for the NABTT CNS Consortium (2007) A phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. J Clin Oncol 25(13):1651–1657CrossRefPubMed Nabors B, Mikkelsen T, Rosenfeld S, Hochberg F, Shastry Akella N, Fisher J, Cloud G, Zhang Y, Carson K, Wittemer S, Colvevas D, Grossman S, for the NABTT CNS Consortium (2007) A phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. J Clin Oncol 25(13):1651–1657CrossRefPubMed
26.
Zurück zum Zitat Abdollahi A, Griggs DW, Zieher H, Roth A, Lipson KE, Saffrich R, Grone HJ, Hallahan DE, Reisfeld RA, Debus J, Niethammer AG, Huber PE (2005) Inhibition of alpha(V)beta3 integrin survival signaling enhances antiangiogenic and antitumor effects of radiotherapy. Clin Cancer Res 11(17):6270–6279CrossRefPubMed Abdollahi A, Griggs DW, Zieher H, Roth A, Lipson KE, Saffrich R, Grone HJ, Hallahan DE, Reisfeld RA, Debus J, Niethammer AG, Huber PE (2005) Inhibition of alpha(V)beta3 integrin survival signaling enhances antiangiogenic and antitumor effects of radiotherapy. Clin Cancer Res 11(17):6270–6279CrossRefPubMed
29.
Zurück zum Zitat Monnier Y, Farmer P, Bieler G, Imaizumi N, Sengstag T, Alghisi GC, Stehle JC, Ciarloni L, Andrejevic-Blant S, Moeckli R, Mirimanoff RO, Goodman SL, Delorenzi M, Ruegg C (2008) Cyr61 and alphaVbeta5 integrin cooperate to promote invasion and metastasis of tumors growing in preirradiated stroma. Cancer Res 68(18):7323–7331. doi:10.1158/0008-5472.CAN-08-0841 CrossRefPubMed Monnier Y, Farmer P, Bieler G, Imaizumi N, Sengstag T, Alghisi GC, Stehle JC, Ciarloni L, Andrejevic-Blant S, Moeckli R, Mirimanoff RO, Goodman SL, Delorenzi M, Ruegg C (2008) Cyr61 and alphaVbeta5 integrin cooperate to promote invasion and metastasis of tumors growing in preirradiated stroma. Cancer Res 68(18):7323–7331. doi:10.​1158/​0008-5472.​CAN-08-0841 CrossRefPubMed
31.
Zurück zum Zitat Mitjans F, Sander D, Adan J, Sutter A, Martinez JM, Jaggle CS, Moyano JM, Kreysch HG, Piulats J, Goodman SL (1995) An anti-alpha V-integrin antibody that blocks integrin function inhibits the development of a human melanoma in nude mice. J Cell Sci 108(Pt 8):2825–2838PubMed Mitjans F, Sander D, Adan J, Sutter A, Martinez JM, Jaggle CS, Moyano JM, Kreysch HG, Piulats J, Goodman SL (1995) An anti-alpha V-integrin antibody that blocks integrin function inhibits the development of a human melanoma in nude mice. J Cell Sci 108(Pt 8):2825–2838PubMed
33.
Zurück zum Zitat Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Vinals F, Inoue M, Bergers G, Hanahan D, Casanovas O (2009) Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15(3):220–231. doi:10.1016/j.ccr.2009.01.027 CrossRefPubMed Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Vinals F, Inoue M, Bergers G, Hanahan D, Casanovas O (2009) Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15(3):220–231. doi:10.​1016/​j.​ccr.​2009.​01.​027 CrossRefPubMed
34.
Zurück zum Zitat Xiong JP, Stehle T, Zhang R, Joachimiak A, Frech M, Goodman SL, Arnaout MA (2002) Crystal structure of the extracellular segment of integrin alphaVbeta3 in complex with an arg-gly-asp ligand. Science 296(5565):151–155. doi:10.1126/science1069040 CrossRefPubMed Xiong JP, Stehle T, Zhang R, Joachimiak A, Frech M, Goodman SL, Arnaout MA (2002) Crystal structure of the extracellular segment of integrin alphaVbeta3 in complex with an arg-gly-asp ligand. Science 296(5565):151–155. doi:10.​1126/​science1069040 CrossRefPubMed
35.
Zurück zum Zitat Goodman SL, Holzemann G, Sulyok GA, Kessler H (2002) Nanomolar small molecule inhibitors for alphaV(beta)6, alphaV(beta)5, and alphaV(beta)3 integrins. J Med Chem 45(5):1045–1051. doi:jm0102598 CrossRefPubMed Goodman SL, Holzemann G, Sulyok GA, Kessler H (2002) Nanomolar small molecule inhibitors for alphaV(beta)6, alphaV(beta)5, and alphaV(beta)3 integrins. J Med Chem 45(5):1045–1051. doi:jm0102598 CrossRefPubMed
37.
Zurück zum Zitat MacDonald TJ, Taga T, Shimada H, Tabrizi P, Zlokovic BV, Cheresh DA, Laug WE (2001) Preferential susceptibility of brain tumors to the antiangiogenic effects of an alpha(V) integrin antagonist. Neurosurgery 48(1):151–157CrossRefPubMed MacDonald TJ, Taga T, Shimada H, Tabrizi P, Zlokovic BV, Cheresh DA, Laug WE (2001) Preferential susceptibility of brain tumors to the antiangiogenic effects of an alpha(V) integrin antagonist. Neurosurgery 48(1):151–157CrossRefPubMed
38.
Zurück zum Zitat Eskens FA, Dumez H, Hoekstra R, Perschl A, Brindley C, Bottcher S, Wynendaele W, Drevs J, Verweij J, van Oosterom AT (2003) Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of cilengitide (EMD 121974), a novel inhibitor of the integrins alphavbeta3 and alphavbeta5 in patients with advanced solid tumours. Eur J Cancer 39(7):917–926. doi:S0959804903000571 CrossRefPubMed Eskens FA, Dumez H, Hoekstra R, Perschl A, Brindley C, Bottcher S, Wynendaele W, Drevs J, Verweij J, van Oosterom AT (2003) Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of cilengitide (EMD 121974), a novel inhibitor of the integrins alphavbeta3 and alphavbeta5 in patients with advanced solid tumours. Eur J Cancer 39(7):917–926. doi:S095980490300057​1 CrossRefPubMed
39.
Zurück zum Zitat MacDonald TJ, Stewart CF, Kocak M, Goldman S, Ellenbogen RG, Phillips P, Lafond D, Poussaint TY, Kieran MW, Boyett JM, Kun LE (2008) Phase I clinical trial of cilengitide in children with refractory brain tumors: pediatric brain tumor consortium study pbtc-012. J Clin Oncol 26(6):919–924. doi:10.1200/JCO.2007.14.1812 CrossRefPubMed MacDonald TJ, Stewart CF, Kocak M, Goldman S, Ellenbogen RG, Phillips P, Lafond D, Poussaint TY, Kieran MW, Boyett JM, Kun LE (2008) Phase I clinical trial of cilengitide in children with refractory brain tumors: pediatric brain tumor consortium study pbtc-012. J Clin Oncol 26(6):919–924. doi:10.​1200/​JCO.​2007.​14.​1812 CrossRefPubMed
40.
Zurück zum Zitat Stupp R, Ruegg C (2007) Integrin inhibitors reaching the clinic. J Clin Oncol 25(13):1637–1638CrossRefPubMed Stupp R, Ruegg C (2007) Integrin inhibitors reaching the clinic. J Clin Oncol 25(13):1637–1638CrossRefPubMed
41.
Zurück zum Zitat Reardon DA, Fink KL, Mikkelsen T, Cloughesy TF, O’Neill A, Plotkin S, Glantz M, Ravin P, Raizer JJ, Rich KM, Schiff D, Shapiro WR, Burdette-Radoux S, Dropcho EJ, Wittemer SM, Nippgen J, Picard M, Nabors LB (2008) Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. J Clin Oncol 26(34):5610–5617. doi:10.1200/JCO.2008.16.7510 CrossRefPubMed Reardon DA, Fink KL, Mikkelsen T, Cloughesy TF, O’Neill A, Plotkin S, Glantz M, Ravin P, Raizer JJ, Rich KM, Schiff D, Shapiro WR, Burdette-Radoux S, Dropcho EJ, Wittemer SM, Nippgen J, Picard M, Nabors LB (2008) Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. J Clin Oncol 26(34):5610–5617. doi:10.​1200/​JCO.​2008.​16.​7510 CrossRefPubMed
42.
Zurück zum Zitat Fink K, Mikkelsen T, Nabors LB, Ravin P, Plotkin SR, Schiff D, Hicking C, Picard M, Reardon DA (2010) Long-term effects of cilengitide, a novel integrin inhibitor, in recurrent glioblastoma: a randomized phase IIa study. Proc Am Soc Clin Oncol, J Clin Oncol 28(suppl):15s, abstract 2010 Fink K, Mikkelsen T, Nabors LB, Ravin P, Plotkin SR, Schiff D, Hicking C, Picard M, Reardon DA (2010) Long-term effects of cilengitide, a novel integrin inhibitor, in recurrent glioblastoma: a randomized phase IIa study. Proc Am Soc Clin Oncol, J Clin Oncol 28(suppl):15s, abstract 2010
43.
Zurück zum Zitat Nabors L, Mikkelsen T, Batchelor T, Lesser G, Rosenfeld M, Ye X, Piantadosi S, Olson J, Brem S, Grossman S (2009) Nabtt 0306: A randomized phase II trial of EMD 121974 in conjunction with concomitant and adjuvant temozolomide with radiation therapy in patients with newly diagnosed glioblastoma multiforme (GBM). Proc Am Soc Clin Oncol, J Clin Oncol 27:15s, suppl; abstract 2001 Nabors L, Mikkelsen T, Batchelor T, Lesser G, Rosenfeld M, Ye X, Piantadosi S, Olson J, Brem S, Grossman S (2009) Nabtt 0306: A randomized phase II trial of EMD 121974 in conjunction with concomitant and adjuvant temozolomide with radiation therapy in patients with newly diagnosed glioblastoma multiforme (GBM). Proc Am Soc Clin Oncol, J Clin Oncol 27:15s, suppl; abstract 2001
44.
Zurück zum Zitat Gilbert M, Lamborn K, Lassman A, Cloughesy T, Chang S, Lieberman F, Wen P, Poetzsch S, Picard M, Prados M, Kuhn J, for the North American Brain Tumor Consortium (2007) Tumor tissue delivery of cilengitide fater intravenous administration to patients with recurrent glioblastoma. Preliminary data from NABTC protocol 03–02. Neuro Oncol 4:525 Gilbert M, Lamborn K, Lassman A, Cloughesy T, Chang S, Lieberman F, Wen P, Poetzsch S, Picard M, Prados M, Kuhn J, for the North American Brain Tumor Consortium (2007) Tumor tissue delivery of cilengitide fater intravenous administration to patients with recurrent glioblastoma. Preliminary data from NABTC protocol 03–02. Neuro Oncol 4:525
45.
Zurück zum Zitat Stupp R, Hegi ME, Neyns B, Goldbrunner R, Schlegel U, Clement PM, Grabenbauer GG, Ochsenbein AF, Simon M, Dietrich PY, Pietsch T, Hicking C, Tonn JC, Diserens AC, Pica A, Hermisson M, Krueger S, Picard M, Weller M (2010) Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma. J Clin Oncol 28(16):2712–2718. doi:10.1200/JCO.2009.26.6650 CrossRefPubMed Stupp R, Hegi ME, Neyns B, Goldbrunner R, Schlegel U, Clement PM, Grabenbauer GG, Ochsenbein AF, Simon M, Dietrich PY, Pietsch T, Hicking C, Tonn JC, Diserens AC, Pica A, Hermisson M, Krueger S, Picard M, Weller M (2010) Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma. J Clin Oncol 28(16):2712–2718. doi:10.​1200/​JCO.​2009.​26.​6650 CrossRefPubMed
46.
Zurück zum Zitat Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996CrossRefPubMed Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996CrossRefPubMed
47.
Zurück zum Zitat Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10(5):459–466. doi:10.1016/S1470-2045(09)70025-7 CrossRefPubMed Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10(5):459–466. doi:10.​1016/​S1470-2045(09)70025-7 CrossRefPubMed
48.
Zurück zum Zitat Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10):997–1003CrossRefPubMed Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10):997–1003CrossRefPubMed
49.
Zurück zum Zitat Stupp R, Van Den Bent MJ, Erridge SC, Reardon DA, Hong Y, Wheeler H, Hegi M, Perry JR, Picard M, Weller M (2010) Cilengitide in newly diagnosed glioblastoma with MGMT promoter methylation: protocol of a multicenter, randomized, open-label, controlled phase III trial (CENTRIC). Proc Am Soc Clin Oncol, J Clin Oncol 28:15s, suppl; abstr TPS152 Stupp R, Van Den Bent MJ, Erridge SC, Reardon DA, Hong Y, Wheeler H, Hegi M, Perry JR, Picard M, Weller M (2010) Cilengitide in newly diagnosed glioblastoma with MGMT promoter methylation: protocol of a multicenter, randomized, open-label, controlled phase III trial (CENTRIC). Proc Am Soc Clin Oncol, J Clin Oncol 28:15s, suppl; abstr TPS152
Metadaten
Titel
Targeting integrins in malignant glioma
verfasst von
Ghazaleh Tabatabai
Michael Weller
Burt Nabors
Martin Picard
David Reardon
Tom Mikkelsen
Curzio Ruegg
Roger Stupp
Publikationsdatum
01.09.2010
Verlag
Springer-Verlag
Erschienen in
Targeted Oncology / Ausgabe 3/2010
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-010-0156-3

Weitere Artikel der Ausgabe 3/2010

Targeted Oncology 3/2010 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.