[en] BACKGROUND: Glioblastoma multiforme (GBM) has a very poor prognosis and novel treatment strategies are urgently needed. GBM appears to be an optimal target for anti-angiogenic therapy as the tumour shows a high degree of endothelial cell proliferation and pro-angiogenic growth factor expression. OBJECTIVE: To examine the role of angiogenic factors (particularly VEGF) in glioma and whether inhibition of these factors can be used as a treatment. METHODS: A review of relevant literature. RESULTS/CONCLUSIONS: Anti-angiogenic therapy has fulfilled the proof of concept in glioma animal models. In glioma patients, the efficacy of anti-angiogenic mono-therapies initially has been disappointing. However recent clinical trials combining bevacizumab, an anti-VEGF antibody, with chemotherapy reported very encouraging response rates. Although randomized phase III clinical trials with anti-angiogenic molecules are not yet available for GBM patients, this treatment regimen is already applied off protocol in several clinical centers. It should be kept in mind though that tumours can develop escape mechanisms. In particular invasive cells, which migrate away from the highly vascularized tumour core, are not targeted by anti-angiogenic therapies. In our opinion, the future of anti-angiogenic therapy will rely on a combination strategy including chemotherapy and drugs that target invasive glioma cells.
Disciplines :
Oncologie
Auteur, co-auteur :
Miletic, Hrvoje; Department of Biomedicine, University of Bergen, NorLux Neuro-Oncology, Bergen, Norway. Hrvoje.Miletic@biomed.uib.no
NICLOU, Simone P. ; NorLux Neuro-Oncology Laboratory, CRP-Santé, Luxembourg
Johansson, Mikael
Bjerkvig, Rolf
Co-auteurs externes :
yes
Langue du document :
Anglais
Titre :
Anti-VEGF therapies for malignant glioma: treatment effects and escape mechanisms.
Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007;114(2):97-109
Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med 2008;359(5):492-507
Wrensch M, Minn Y, Chew T, et al. Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro Oncol 2002;4(4):278-299
Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352(10):987-996 (Pubitemid 40349501)
Sathornsumetee S, Rich JN. Antiangiogenic therapy in malignant glioma: promise and challenge. Curr Pharm Des 2007;13(35):3545-3558 (Pubitemid 350238925)
Holash J, Maisonpierre PC, Compton D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 1999;284(5422):1994-1998 •• First paper confirming the concept of vessel co-option. (Pubitemid 29309448)
Leenders WP, Kusters B, de Waal RM. Vessel co-option: how tumors obtain blood supply in the absence of sprouting angiogenesis. Endothelium 2002;9(2):83-87 (Pubitemid 35252016)
Sakariassen PO, Prestegarden L, Wang J, et al. Angiogenesis-independent tumor growth mediated by stem-like cancer cells. Proc Natl Acad Sci USA 2006;103(44):16466-16471 •• First study showing growth of glioblastoma independent of angiogenesis. (Pubitemid 44715219)
Jain RK, di Tomaso E, Duda DG, et al. Angiogenesis in brain tumours. Nat Rev Neurosci 2007;8(8):610-622 •• Excellent review about angiogenesis in brain tumors. (Pubitemid 47093931)
Plate KH, Breier G, Millauer B, et al. Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. Cancer Res 1993;53(23):5822-5827 (Pubitemid 23360294)
Plate KH, Risau W. Angiogenesis in malignant gliomas. Glia 1995;15(3):339-347
Duda DG, Cohen KS, Kozin SV, et al. Evidence for incorporation of bone marrow-derived endothelial cells into perfused blood vessels in tumors. Blood 2006;107(7):2774-2776
Santarelli JG, Udani V, Yung YC, et al. Incorporation of bone marrow-derived Flk-1-expressing CD34+ cells in the endothelium of tumor vessels in the mouse brain. Neurosurgery 2006;59(2):374-82; discussion-82 (Pubitemid 44325883)
Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407(6801):249-257 •• General concepts of angiogenesis.
Yano S, Shinohara H, Herbst RS, et al. Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis. Cancer Res 2000;60(17):4959-4967 (Pubitemid 30701515)
Folberg R, Hendrix MJ, Maniotis AJ. Vasculogenic mimicry and tumor angiogenesis. Am J Pathol 2000;156(2):361-381 • Discussion of vasculogenic mimicry. (Pubitemid 30648785)
McDonald DM, Munn L, Jain RK. Vasculogenic mimicry: how convincing, how novel, and how significant? Am J Pathol 2000;156(2):383-388 • Discussion of vasculogenic mimicry.
Zhang S, Zhang D, Sun B. Vasculogenic mimicry: current status and future prospects. Cancer Lett 2007;254(2):157-164 (Pubitemid 47126687)
Yue WY, Chen ZP. Does vasculogenic mimicry exist in astrocytoma? J Histochem Cytochem 2005;53(8):997-1002
Roy H, Bhardwaj S, Yla-Herttuala S. Biology of vascular endothelial growth factors. FEBS Lett 2006;580(12):2879-2887 (Pubitemid 43729175)
Senger DR, Galli SJ, Dvorak AM, et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983;219(4587):983-985 • Initial paper about VEGFexpression in tumors.
Keck PJ, Hauser SD, Krivi G, et al. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 1989;246(4935):1309-1312 •• First study showing that VEGF is an endothelial cell mitogen. (Pubitemid 20066717)
Leung DW, Cachianes G, Kuang WJ, et al. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989;246(4935):1306-1309 (Pubitemid 20066716)
Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9(6):669-676 •• Excellent general review about VEGF. (Pubitemid 36749215)
Houck KA, Ferrara N, Winer J, et al. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol 1991;5(12):1806-1814
Tischer E, Mitchell R, Hartman T, et al. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 1991;266(18):11947-11954 (Pubitemid 21907041)
Robinson CJ, Stringer SE. The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J Cell Sci 2001;114(Pt 5):853-865 (Pubitemid 32273121)
Plate KH. Mechanisms of angiogenesis in the brain. J Neuropathol Exp Neurol 1999;58(4):313-320 (Pubitemid 29187893)
Plate KH, Breier G, Weich HA, Risau W. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 1992;359(6398):845-848 •• Initial paper about VEGF in brain tumors.
Shweiki D, Itin A, Neufeld G, et al. Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. J Clin Invest 1993;91(5):2235-2243 (Pubitemid 23141500)
Rak J, Yu JL. Oncogenes and tumor angiogenesis: the question of vascular "supply" and vascular "demand". Semin Cancer Biol 2004;14(2):93-104
Pal S, Datta K, Mukhopadhyay D. Central role of p53 on regulation of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) expression in mammary carcinoma. Cancer Res 2001;61(18):6952-6957 • Study showing that tumor suppressor genes, in particular p53, can suppress VEGF expression. (Pubitemid 32896524)
Zhang L, Yu D, Hu M, et al. Wild-type p53 suppresses angiogenesis in human leiomyosarcoma and synovial sarcoma by transcriptional suppression of vascular endothelial growth factor expression. Cancer Res 2000;60(13):3655-3661 (Pubitemid 30482190)
Ohh M, Kaelin WG Jr. The von Hippel-Lindau tumour suppressor protein: new perspectives. Mol Med Today 1999;5(6):257-263 (Pubitemid 29282464)
Cohen T, Nahari D, Cerem LW, et al. Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem 1996;271(2):736-741 (Pubitemid 26034921)
Pertovaara L, Kaipainen A, Mustonen T, et al. Vascular endothelial growth factor is induced in response to transforming growth factor-β in fibroblastic and epithelial cells. J Biol Chem 1994;269(9):6271-6274 (Pubitemid 24190991)
Tsai JC, Goldman CK, Gillespie GY. Vascular endothelial growth factor in human glioma cell lines: induced secretion by EGF, PDGF-BB, and bFGF. J Neurosurg 1995;82(5):864-873 • VEGF expression can be stimulated by several growth factors.
Samoto K, Ikezaki K, Ono M, et al. Expression of vascular endothelial growth factor and its possible relation with neovascularization in human brain tumors. Cancer Res 1995;55(5):1189-1193
Schmidt NO, Westphal M, Hagel C, et al. Levels of vascular endothelial growth factor, hepatocyte growth factor/scatter factor and basic fibroblast growth factor in human gliomas and their relation to angiogenesis. Int J Cancer 1999;84(1):10-18 (Pubitemid 29059101)
Brown LF, Berse B, Jackman RW, et al. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer. Hum Pathol 1995;26(1):86-91
Guidi AJ, Abu-Jawdeh G, Berse B, et al. Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia. J Natl Cancer Inst 1995;87(16):1237-1245
Wong MP, Cheung N, Yuen ST, et al. Vascular endothelial growth factor is up-regulated in the early pre-malignant stage of colorectal tumour progression. Int J Cancer 1999;81(6):845-850 (Pubitemid 29249965)
Nagy JA, Benjamin L, Zeng H, et al. Vascular permeability, vascular hyperpermeability and angiogenesis. Angiogenesis 2008;11(2):109-119
Kaal EC, Vecht CJ. The management of brain edema in brain tumors. Curr Opin Oncol 2004;16(6):593-600 (Pubitemid 39482980)
Brown LF, Detmar M, Claffey K, et al. Vascular permeability factor/vascular endothelial growth factor: a multifunctional angiogenic. cytokine Exs 1997;79:233-269
Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995;146(5):1029-1039 •• Excellent general review about VEGF.
Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J Mol Med 1999;77(7):527-543 •• Excellent general review about VEGF. (Pubitemid 29426311)
Benjamin LE, Golijanin D, Itin A, et al. Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest 1999;103(2):159-165 (Pubitemid 29053133)
Shibuya M. Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): a dual regulator for angiogenesis. Angiogenesis 2006;9(4):225-30; discussion 31
Lambrechts D, Storkebaum E, Carmeliet P. VEGF: necessary to prevent motoneuron degeneration, sufficient to treat ALS? Trends Mol Med 2004;10(6):275-282
Carmeliet P, Tessier-Lavigne M. Common mechanisms of nerve and blood vessel wiring. Nature 2005;436(7048):193-200 •• Excellent review on similarities in mechanisms between axonal guidance and angiogenesis. (Pubitemid 41021263)
Greenberg DA, Jin K. From angiogenesis to neuropathology. Nature 2005;438(7070):954-959 •• Role of angiogenic factors in the brain under physiological and pathological conditions. (Pubitemid 43093961)
Bielenberg DR, Pettaway CA, Takashima S, Klagsbrun M. Neuropilins in neoplasms: expression, regulation, and function. Exp Cell Res 2006;312(5):584-593 (Pubitemid 43290335)
Pellet-Many C, Frankel P, Jia H, Zachary I. Neuropilins: structure, function and role in disease. Biochem J 2008;411(2):211-226 (Pubitemid 351580173)
Soker S, Takashima S, Miao HQ, et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 1998;92(6):735-745 •• Discovery of neuropilin-1 as a co-receptor for VEGF. (Pubitemid 28155313)
Soker S, Miao HQ, Nomi M, et al. VEGF165 mediates formation of complexes containing VEGFR-2 and neuropilin-1 that enhance VEGF165-receptor binding. J Cell Biochem 2002;85(2):357-368 (Pubitemid 34274903)
Ellis LM. The role of neuropilins in cancer. Mol Cancer Ther 2006;5(5):1099-1107 (Pubitemid 43881301)
Ding H, Wu X, Roncari L, et al. Expression and regulation of neuropilin-1 in human astrocytomas. Int J Cancer 2000;88(4):584-592 (Pubitemid 30805073)
Broholm H, Laursen H. Vascular endothelial growth factor (VEGF) receptor neuropilin-1's distribution in astrocytic tumors. Apmis 2004;112(4-5):257-263 (Pubitemid 39005907)
Hu B, Guo P, Bar-Joseph I, et al. Neuropilin-1 promotes human glioma progression through potentiating the activity of the HGF/SF autocrine pathway. Oncogene 2007;26(38):5577-5586 • Influence of Nrp1 on tumor progression in glioma. (Pubitemid 47267840)
Wang L, Zeng H, Wang P, et al. Neuropilin-1-mediated vascular permeability factor/vascular endothelial growth factor-dependent endothelial cell migration. J Biol Chem 2003;278(49):48848-48860
Murga M, Fernandez-Capetillo O, Tosato G. Neuropilin-1 regulates attachment in human endothelial cells independently of vascular endothelial growth factor receptor-2. Blood 2005;105(5):1992-1999 • VEGF can activate Nrp1 in absence of VEGFR2. (Pubitemid 40731783)
Pan Q, Chanthery Y, Liang WC, et al. Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell 2007;11(1):53-67 • Additive therapeutic effects blocking Nrp1 and VEGF. (Pubitemid 46054517)
Yancopoulos GD, Davis S, Gale NW, et al. Vascular-specific growth factors and blood vessel formation. Nature 2000;407(6801):242-248 • Review on VEGF and other factors that stimulate angiogenesis.
Reiss Y, Machein MR, Plate KH. The role of angiopoietins during angiogenesis in gliomas. Brain Pathol 2005;15(4):311-317 (Pubitemid 41677430)
Machein MR, Knedla A, Knoth R, et al. Angiopoietin-1 promotes tumor angiogenesis in a rat glioma model. Am J Pathol 2004;165(5):1557-1570 • Angiopoietin-1 supports glioma angiogenesis. (Pubitemid 39435155)
Sun L, Hui AM, Su Q, et al. Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain. Cancer Cell 2006;9(4):287-300 • SCF can activate endothelial cells and an angiogenic response in vivo.
Brat DJ, Bellail AC, Van Meir EG. The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro Oncol 2005;7(2):122-133 (Pubitemid 40590513)
Garkavtsev I, Kozin SV, Chernova O, et al. The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis. Nature 2004;428(6980):328-332 •• ING4 regulates brain tumor angiogenesis through NF-kapp-b. (Pubitemid 38418804)
Bajetto A, Barbieri F, Dorcaratto A, et al. Expression of CXC chemokine receptors 1-5 and their ligands in human glioma tissues: role of CXCR4 and SDF1 in glioma cell proliferation and migration. Neurochem Int 2006;49(5):423-432 (Pubitemid 44189638)
Rempel SA, Dudas S, Ge S, Gutierrez JA. Identification and localization of the cytokine SDF1 and its receptor, CXC chemokine receptor 4, to regions of necrosis and angiogenesis in human glioblastoma. Clin Cancer Res 2000;6(1):102-111 (Pubitemid 30064982)
Zagzag D, Lukyanov Y, Lan L, et al. Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion. Lab Invest 2006;86(12):1221-1232 • CXCR4 is involved in brain tumor angiogenesis. (Pubitemid 44789912)
Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285(21):1182-1186 •• Initial concept of blocking angiogenesis for tumor therapy by Judah Folkman.
Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 2007;370(9605):2103-2111 • Clinical study combining antiangiogenic therapy with chemotherapy. (Pubitemid 350296300)
Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350(23):2335-2342 (Pubitemid 38702844)
Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007;357(26):2666- 2676
Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006;355(24):2542-2550 (Pubitemid 44917502)
Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007;356(2):125-134 • Anti-angiogenic monotherapy for renal cancer. (Pubitemid 46089673)
Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356(2):115-124 (Pubitemid 46089672)
Kim KJ, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 1993;362(6423):841-844 •• First experimental evidence for efficacy of anti-angiogenic treatment. (Pubitemid 23132159)
Rubenstein JL, Kim J, Ozawa T, et al. Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption. Neoplasia 2000;2(4):306-314 •• First experimental evidence of escape mechanisms after anti-angiogenic treatment. (Pubitemid 30703463)
Kunkel P, Ulbricht U, Bohlen P, et al. Inhibition of glioma angiogenesis and growth in vivo by systemic treatment with a monoclonal antibody against vascular endothelial growth factor receptor-2. Cancer Res 2001;61(18):6624-6628 (Pubitemid 32896475)
Ran S, Huang X, Downes A, Thorpe PE. Evaluation of novel antimouse VEGFR2 antibodies as potential antiangiogenic or vascular targeting agents for tumor therapy. Neoplasia 2003;5(4):297-307 (Pubitemid 37048607)
de Bouard S, Herlin P, Christensen JG, et al. Antiangiogenic and anti-invasive effects of sunitinib on experimental human glioblastoma. Neuro Oncol 2007;9(4):412-423
Goldbrunner RH, Bendszus M, Wood J, et al. PTK787/ZK222584, an inhibitor of vascular endothelial growth factor receptor tyrosine kinases, decreases glioma growth and vascularization. Neurosurgery 2004;55(2):426-32; discussion 32 (Pubitemid 39014545)
Jones-Bolin S, Zhao H, Hunter K, et al. The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in orthotopic models of glioblastoma and colon carcinoma in mice. Mol Cancer Ther 2006;5(7):1744-1753 (Pubitemid 44323242)
Mendel DB, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2003;9(1):327-337
Sandstrom M, Johansson M, Andersson U, et al. The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model. Br J Cancer 2004;91(6):1174-1180 (Pubitemid 39336259)
Sandstrom M, Johansson M, Bergstrom P, et al. Effects of the VEGFR inhibitor ZD6474 in combination with radiotherapy and temozolomide in an orthotopic glioma model. J Neurooncol 2008;88(1):1-9
Takamoto T, Sasaki M, Kuno T, Tamaki N. Flk-1 specific kinase inhibitor (SU5416) inhibited the growth of GS-9L glioma in rat brain and prolonged the survival. Kobe J Med Sci 2001;47(4):181-191 (Pubitemid 34101040)
Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res 2007;13(4):1253-1259 •• Clinical trial showing efficacy of combined anti-angiogenic and chemotherapy for glioblastoma.
Chen W, Delaloye S, Silverman DH, et al. Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study. J Clin Oncol 2007;25(30):4714-4721 •• This study confirms treatment effects of a combined antiagiogenic and chemotherapy by PET imaging. (Pubitemid 350086472)
Ali SA, McHayleh WM, Ahmad A, et al. Bevacizumab and irinotecan therapy in glioblastoma multiforme: a series of 13 cases. J Neurosurg 2008;109(2):268-272
Norden AD, Young GS, Setayesh K, et al. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology 2008;70(10):779-787
Poulsen HS, Grunnet K, Sorensen M, et al. Bevacizumab plus irinotecan in the treatment patients with progressive recurrent malignant brain tumours. Acta Oncol 2009;48(1):52-58
Cloughesy T, Prados MD, Wen Y, et al. A Phase II, randomized, non-comparative clinincal trial of the effect of bevacizumab (BV) alone or in combination with irinotecan (CPT) on 6-month progression free survival (PFS6) in recurrent, treatment-refractory glioblastoma (GBM) [abstract 2010b]. J Clin Oncol 2008;26(Suppl)
Glusker P, Recht L, Lane B. Reversible posterior leukoencephalopathy syndrome and bevacizumab. N Engl J Med 2006;354(9):980-2; discussion-2 • Side effects due to antiangiogenic therapy. (Pubitemid 43313687)
Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 2007;25(30):4722-4729 • Side effects due to antiangiogenic therapy.
Lai A, Filka E, McGibbon B, et al. 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 2008;71(5):1372-1380
Available from: http://clinicaltrials.gov
Wedge SR, Ogilvie DJ, Dukes M, et al. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res 2002;62(16):4645-4655 (Pubitemid 34898591)
Willett CG, Boucher Y, di Tomaso E, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 2004;10(2):145-147 (Pubitemid 38524883)
Batchelor TT, Sorensen AG, di Tomaso E, et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 2007;11(1):83-95 •• First clinical evidence that antiangiogenic therapy can normalize tumor vasculature. (Pubitemid 46075199)
Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001;7(9):987-989 •• Excellent review on the concept of normalization of tumor vasculature by anti-angiogenic therapies. (Pubitemid 32937367)
Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005;307(5706):58-62 •• Excellent review on the concept of normalization of tumor vasculature by anti-angiogenic therapies. (Pubitemid 40093472)
Ignatova TN, Kukekov VG, Laywell ED, et al. Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia 2002;39(3):193-206
Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003;63(18):5821-5828 (Pubitemid 37187480)
Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature 2004;432(7015):396-401 •• Concept of cancer stem cells shown for CD133 positive cells in glioblastoma. (Pubitemid 39551674)
Hemmati HD, Nakano I, Lazareff JA, et al. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 2003;100(25):15178-15183 (Pubitemid 37518036)
Galli R, Binda E, Orfanelli U, et al. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 2004;64(19):7011-7021 (Pubitemid 39331011)
Leenders WP, Kusters B, Verrijp K, et al. Antiangiogenic therapy of cerebral melanoma metastases results in sustained tumor progression via vessel co-option. Clin Cancer Res 2004;10(18 Pt 1):6222-6230 (Pubitemid 39287530)
Beier D, Hau P, Proescholdt M, et al. CD133+ and CD133- glioblastomaderived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res 2007;67(9):4010-4015 (Pubitemid 46815044)
Wang J, Sakariassen PO, Tsinkalovsky O, et al. CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells. Int J Cancer 2008;122(4):761-768 •• CD133 negative cells can also initiate glioblastoma.
Kelly PN, Dakic A, Adams JM, et al. Tumor growth need not be driven by rare cancer stem cells. Science 2007;317(5836):337 • Experimental evidence against the cancer stem cell hypothesis.
Lee J, Kotliarova S, Kotliarov Y, et al. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell 2006;9(5):391-403 (Pubitemid 43668737)
Cloughesy TF, Prados MD, Wen PY, et al. A phase II, randomized, non-comparative clinical trial of the effect of bevacizumab (BV) alone or in combination with irinotecan (CPT) on 6-month progression free survival (PFS6) in recurrent, treatment-refractory glioblastoma (GBM) [abstract 2010]. J Clin Oncol 2008;26(Suppl)
Sathornsumetee S, Vredenburgh JJ, Rich JN, et al. Phase II study of bevacizumab and erlotinib in patients with recurrent glioblastoma multiforme [abstract 13008]. J Clin Oncol 2008;26(Suppl)
Rich JN, Desjardins A, Sathornsumetee S, et al. Phase II study of bevacizumab and etoposide in patients with recurrent malignant glioma [abstract 2022]. J Clin Oncol 2008;26(Suppl)
Reardon DA, Fink KL, Mikkelsen T, et al. Randomized Phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. J Clin Oncol 2008;26(34):5610-5617
Stupp R, Goldbrunner RH, Neyns B, et al. Phase I/IIa trial of cilengitide (EMD121974) and temozolomide with concomitant radiotherapy, followed by temozolomide and cilingitide maintenance therapy in patients with newly diagnosed glioblastoma. J Clin Oncol 2007;25(18S):2000
De Groot JF, Wen PY, Lamborn K, et al. Phase II single arm trial of aflibercept in patients with recurrent temozolomide-resistant glioblastoma: NABTC 0601 [abstract 2020]. J Clin Oncol 2008;26(Suppl)
Fine HA, Puduvalli VK, Chamberlain MC, et al. Enzastaurin versus lomustine in the treatment of recurrent, intracranial glioblastoma multiforme: a phase III study [abstract 2005]. J Clin Oncol 2008;26(Suppl)
Butowski NA, Lamborn K, Chang S, et al. Phase I/II study of enzastaurin plus remozolomide and radiation therapy in patients with glioblastoma multiforme or gliosarcoma [abstract 3559]. J Clin Oncol 2008;26(Suppl)
Chaskis C, Sadones J, Michotte A, et al. A Phase II trial of sunitib in patients with recurrent high-grade glioma [abstract 13001]. J Clin Oncol 2008;26(Suppl).
