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Erschienen in: Der Nervenarzt 8/2010

01.08.2010 | Leitthema

Angiogenesehemmung in der Neuroonkologie

Eine vielversprechende Therapiestrategie gegen maligne Gliome

verfasst von: Dr. Dr. G. Tabatabai, R. Stupp

Erschienen in: Der Nervenarzt | Ausgabe 8/2010

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Zusammenfassung

Der Einsatz angiogenesehemmender Substanzen in der Hirntumortherapie nimmt zu. Der initialen Euphorie bezüglich der überraschend hohen Ansprechraten bei Hemmstoffen des VEGF („vascular endothelial growth factor“)-Signalwegs ist mittlerweile eine Ernüchterung gefolgt, da die progressionsfreie Zeit und das mediane Überleben langfristig nicht zufriedenstellend sind. Die Tumorprogression kann während/nach antiangiogener Therapie mit rapider klinisch-neurologischer Verschlechterung einhergehen und weist häufig einen gliomatosisähnlichen diffus-infiltrativen Phänotyp auf. Somit bestehen die aktuellen Herausforderungen darin, Kriterien für den individuellen Einsatz von Angiogenesehemmern zu definieren sowie die unter der Therapie auftretenden Resistenzmechanismen zu entschlüsseln.
Literatur
1.
Zurück zum Zitat Bao S, Wu Q, Sathornsumetee S et al (2006) Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res 66:7843–7848CrossRefPubMed Bao S, Wu Q, Sathornsumetee S et al (2006) Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res 66:7843–7848CrossRefPubMed
2.
Zurück zum Zitat Bao S, Wu Q, Mc Lendon RE, Hao Y et al (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760CrossRefPubMed Bao S, Wu Q, Mc Lendon RE, Hao Y et al (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760CrossRefPubMed
3.
Zurück zum Zitat Batchelor TT, Sorensen AG, Tomaso E di et al (2007) AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11:83–95CrossRefPubMed Batchelor TT, Sorensen AG, Tomaso E di et al (2007) AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11:83–95CrossRefPubMed
4.
Zurück zum Zitat Friedman HS, Prados MD, Wen PY et al (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27:4733–4740CrossRefPubMed Friedman HS, Prados MD, Wen PY et al (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27:4733–4740CrossRefPubMed
5.
Zurück zum Zitat Gilbertson RJ, Rich JN (2007) Making a tumour‚s bed: glioblastomas stem cells and the vascular niche. Nat Rev Cancer 7:733–736CrossRefPubMed Gilbertson RJ, Rich JN (2007) Making a tumour‚s bed: glioblastomas stem cells and the vascular niche. Nat Rev Cancer 7:733–736CrossRefPubMed
6.
Zurück zum Zitat Gonzales J, Kumar AJ, Conrad CA et al (2009) Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol 67:323–326 Gonzales J, Kumar AJ, Conrad CA et al (2009) Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol 67:323–326
7.
Zurück zum Zitat Gutin PH, Iwamoto FM, Beal K et al (2009) Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. Int J Radiat Oncol 75:156–163CrossRef Gutin PH, Iwamoto FM, Beal K et al (2009) Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. Int J Radiat Oncol 75:156–163CrossRef
8.
Zurück zum Zitat Hurtwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucoverin for metastatic colorectal cancer. N Engl J Med 350:2335–2342CrossRef Hurtwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucoverin for metastatic colorectal cancer. N Engl J Med 350:2335–2342CrossRef
9.
Zurück zum Zitat Jain RK (2001) Normalizing tumor vasculature with antiangiogenic therapy: a new paradigm for combination therapy. Nat Med 7:987–989CrossRefPubMed Jain RK (2001) Normalizing tumor vasculature with antiangiogenic therapy: a new paradigm for combination therapy. Nat Med 7:987–989CrossRefPubMed
10.
Zurück zum Zitat Kamoun WS, Ley CD, Farrar CT et al (2009) Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice. J Clin Oncol 27:2542–2552CrossRefPubMed Kamoun WS, Ley CD, Farrar CT et al (2009) Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice. J Clin Oncol 27:2542–2552CrossRefPubMed
11.
Zurück zum Zitat Kreisl TN, Kim L, Moore K et al (2009) Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 27:740–745CrossRefPubMed Kreisl TN, Kim L, Moore K et al (2009) Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 27:740–745CrossRefPubMed
12.
Zurück zum Zitat Lai A, Filka E, McGibbon B et al (2008) Phase II pilot study of bevacizumab in combination with temozolomide and regional radiation therapy for up-front treatment of patients with newly diagnosed glioblastoma multiforme: Interim analysis of safety and tolerability. Int J Radiat Oncol Biol Phys 71:1372–1380PubMed Lai A, Filka E, McGibbon B et al (2008) Phase II pilot study of bevacizumab in combination with temozolomide and regional radiation therapy for up-front treatment of patients with newly diagnosed glioblastoma multiforme: Interim analysis of safety and tolerability. Int J Radiat Oncol Biol Phys 71:1372–1380PubMed
13.
14.
Zurück zum Zitat Louis DN, Ohgaki H, Wiestler OD et al (2007) The WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109CrossRefPubMed Louis DN, Ohgaki H, Wiestler OD et al (2007) The WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109CrossRefPubMed
15.
Zurück zum Zitat MacDonald TJ, Stewart CF, Kocak M et al (2008) Phase I clinical trial of cilengitide in children with refractory brain tumors: pediatric brain tumor consortium study PBTC-012. J Clin Oncol 26:919–924CrossRefPubMed MacDonald TJ, Stewart CF, Kocak M et al (2008) Phase I clinical trial of cilengitide in children with refractory brain tumors: pediatric brain tumor consortium study PBTC-012. J Clin Oncol 26:919–924CrossRefPubMed
16.
Zurück zum Zitat Maurer GD, Tritschler I, Adams B et al (2009) Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro. Neuro-oncol 11:747–756 Maurer GD, Tritschler I, Adams B et al (2009) Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro. Neuro-oncol 11:747–756
17.
Zurück zum Zitat Mikkelsen T, Brodie C, Finiss S et al (2009) Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule-dependency. Int J Cancer 124:2719–2727CrossRefPubMed Mikkelsen T, Brodie C, Finiss S et al (2009) Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule-dependency. Int J Cancer 124:2719–2727CrossRefPubMed
18.
Zurück zum Zitat Nabors LB, Mikkelsen T, Rosenfeld SS et al (2007) Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. J Clin Oncol 25:1651–1657CrossRefPubMed Nabors LB, Mikkelsen T, Rosenfeld SS et al (2007) Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. J Clin Oncol 25:1651–1657CrossRefPubMed
19.
Zurück zum Zitat Norden AD, Young GS, Setayesh K et al (2008) Bevacizumab for recurrent malignant gliomas. Efficacy, toxicity, and patterns of recurrence. Neurology 70:779–787CrossRefPubMed Norden AD, Young GS, Setayesh K et al (2008) Bevacizumab for recurrent malignant gliomas. Efficacy, toxicity, and patterns of recurrence. Neurology 70:779–787CrossRefPubMed
20.
Zurück zum Zitat Reardon D, Fink KL, Mikkelsen T et al (2008) Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastomas multiforme. J Clin Oncol 26:5610–5617CrossRefPubMed Reardon D, Fink KL, Mikkelsen T et al (2008) Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastomas multiforme. J Clin Oncol 26:5610–5617CrossRefPubMed
21.
Zurück zum Zitat Stark-Vance V (2005) Bevacizumab and CPT-11 in the treatment of relapsed malignant glioma. In: World Federation of Neuro-Oncology Second Quadrennial Meeting, Edinburgh, Scotland (Abstr 342) Stark-Vance V (2005) Bevacizumab and CPT-11 in the treatment of relapsed malignant glioma. In: World Federation of Neuro-Oncology Second Quadrennial Meeting, Edinburgh, Scotland (Abstr 342)
22.
Zurück zum Zitat Stupp R, Mason WP, Bent MJ van den et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide in glioblastoma. N Engl J Med 10:997–1003 Stupp R, Mason WP, Bent MJ van den et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide in glioblastoma. N Engl J Med 10:997–1003
23.
Zurück zum Zitat Stupp R, Hegi ME, Mason WP et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastomas in a randomized phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466CrossRefPubMed Stupp R, Hegi ME, Mason WP et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastomas in a randomized phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466CrossRefPubMed
24.
Zurück zum Zitat Stupp R, Hegi ME, Neyns B et al (2010) Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosted glioblastoma. J Clin Oncol epub ahead of print Stupp R, Hegi ME, Neyns B et al (2010) Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosted glioblastoma. J Clin Oncol epub ahead of print
25.
Zurück zum Zitat Taga T, Suzuki A, Gonzales-Gomez I et al (2002) Alpha v-integrin antagonist EMD 121974 induces apoptosis in brain tumor cells growing on vitronectin and tenascin. Int J Cancer 98:690–697CrossRefPubMed Taga T, Suzuki A, Gonzales-Gomez I et al (2002) Alpha v-integrin antagonist EMD 121974 induces apoptosis in brain tumor cells growing on vitronectin and tenascin. Int J Cancer 98:690–697CrossRefPubMed
26.
Zurück zum Zitat Vredenburgh JJ, Desjardins A, Herndon JE et al (2007) Bevacizumab plus irinotecan in recurrent glioblastom multiforme. J Clin Oncol 25:4722–4729CrossRefPubMed Vredenburgh JJ, Desjardins A, Herndon JE et al (2007) Bevacizumab plus irinotecan in recurrent glioblastom multiforme. J Clin Oncol 25:4722–4729CrossRefPubMed
27.
Zurück zum Zitat Wick W, Weller M, Bent M van den et al (2010) Bevacizumab and recurrent malignant gliomas: a European perspective. J Clin Oncol 28:e188–e189CrossRefPubMed Wick W, Weller M, Bent M van den et al (2010) Bevacizumab and recurrent malignant gliomas: a European perspective. J Clin Oncol 28:e188–e189CrossRefPubMed
28.
Zurück zum Zitat Winkler F, Kozin SV, Tong RT et al (2004) Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1 and matrix metalloproteinases. Cancer Cell 6:553–563PubMed Winkler F, Kozin SV, Tong RT et al (2004) Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1 and matrix metalloproteinases. Cancer Cell 6:553–563PubMed
29.
Zurück zum Zitat Wen PY, Macdonald DR, Reardon DA et al (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972CrossRefPubMed Wen PY, Macdonald DR, Reardon DA et al (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972CrossRefPubMed
Metadaten
Titel
Angiogenesehemmung in der Neuroonkologie
Eine vielversprechende Therapiestrategie gegen maligne Gliome
verfasst von
Dr. Dr. G. Tabatabai
R. Stupp
Publikationsdatum
01.08.2010
Verlag
Springer-Verlag
Erschienen in
Der Nervenarzt / Ausgabe 8/2010
Print ISSN: 0028-2804
Elektronische ISSN: 1433-0407
DOI
https://doi.org/10.1007/s00115-010-2957-0

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