Therapeutic targeting of VEGF in the treatment of glioblastoma

Expert Opinion on Therapeutic Targets

Volumn 16, Issue 10, 2012, Pages 973-984

  Robles Irizarry, Lizbeth ^a   Hambardzumyan, Dolores ^a   Nakano, Ichiro ^b   Gladson, Candece L ^a   Ahluwalia, Manmeet S ^a,c  

^a LERNER RESEARCH INSTITUTE   (United States)

^b OHIO STATE UNIVERSITY   (United States)

^c CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Angiogenesis; Glioblastoma; Targeted therapy; VEGF

Indexed keywords

6 [4 (4 ETHYL 1 PIPERAZINYLMETHYL)PHENYL] 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; AFLIBERCEPT; BEVACIZUMAB; CABOZANTINIB; CARBOPLATIN; CEDIRANIB; CETUXIMAB; IRINOTECAN; LOMUSTINE; PAZOPANIB; PLACEBO; RAMUCIRUMAB; SORAFENIB; SUNITINIB; TEMOZOLOMIDE; VANDETANIB; VASCULOTROPIN; VATALANIB;

ANGIOGENESIS; CANCER COMBINATION CHEMOTHERAPY; CANCER RADIOTHERAPY; DRUG EFFICACY; DRUG TARGETING; GLIOBLASTOMA; HUMAN; PROGRESSION FREE SURVIVAL; REVIEW;

ANGIOGENESIS INHIBITORS; ANIMALS; BRAIN NEOPLASMS; DRUG RESISTANCE, NEOPLASM; GLIOBLASTOMA; HUMANS; NEOVASCULARIZATION, PATHOLOGIC; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84866504364     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2012.711817     Document Type: Review

References (111)

1. Kohler BA, Ward E, McCarthy BJ, et al. Annual report to the nation on the status of cancer, 1975-2007, featuring tumors of the brain and other nervous system. J Natl Cancer Inst 2011;103(9):714-36
2. CBTRUS. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2004-2008 (March 23, 2012 Revision) Central Brain Tumor Registry of the United States, Hinsdale, IL. 2012.Available from: www.cbtrus.org
3. Phillips HS, Kharbanda S, Chen R, et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 2006;9(3):157-73 (Pubitemid 43357943)
4. Verhaak RG, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010;17(1):98-110
5. 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):987-96 (Pubitemid 40349501)
6. Brem S, Cotran R, Folkman J. Tumor angiogenesis: a quantitative method for histologic grading. J Natl Cancer Inst 1972;48(2):347-56
7. Kleihues P, Louis DN, Scheithauer BW, et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 2002;61(3):215-25; discussion 26-9 (Pubitemid 34212595)
8. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 1990;82(1):4-6 (Pubitemid 20020880)
9. Baluk P,Morikawa S, Haskell A, et al. Abnormalities of basement membrane on blood vessels and endothelial sprouts in tumors. Am J Pathol 2003;163(5):1801-15 (Pubitemid 37310012)
10. Vitolo D, Paradiso P, Uccini S, et al. Expression of adhesion molecules and extracellular matrix proteins in glioblastomas: relation to angiogenesis and spread. Histopathology 1996;28(6):521-8 (Pubitemid 26192947)
11. Jain RK, di Tomaso E, Duda DG, et al. Angiogenesis in brain tumours. Nat Rev Neurosci 2007;8(8):610-22 (Pubitemid 47093931)
12. Wang GL, Semenza GL. Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia. J Biol Chem 1993;268(29):21513-18 (Pubitemid 23320639)
13. Tanimoto K, Makino Y, Pereira T, Poellinger L. Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von Hippel-Lindau tumor suppressor protein. EMBO J 2000;19(16):4298-309 (Pubitemid 30623741)
14. Salceda S, Caro J. Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes. J Biol Chem 1997;272(36):22642-7 (Pubitemid 27386079)
15. Semenza G. Signal transduction to hypoxia-inducible factor 1. Biochem Pharmacol 2002;64(5-6):993-8 (Pubitemid 35232274)
16. Kelly BD, Hackett SF, Hirota K, et al. Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor. Circ Res 2003;93(11):1074-81 (Pubitemid 37485038)
17. Krishnamachary B, Berg-Dixon S, Kelly B, et al. Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res 2003;63(5):1138-43 (Pubitemid 36278449)
18. Kaur B, Khwaja FW, Severson EA, et al. Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. Neuro Oncol 2005;7(2):134-53 (Pubitemid 40590514)
19. Fischer I, Gagner JP, Law M, et al. Angiogenesis in gliomas: biology and molecular pathophysiology. Brain Pathol 2005;15(4):297-310 (Pubitemid 41677429)
20. Kargiotis O, Rao JS, Kyritsis AP. Mechanisms of angiogenesis in gliomas. J Neurooncol 2006;78(3):281-93 (Pubitemid 44018823)
21. Rahman R, Smith S, Rahman C, Grundy R. Antiangiogenic therapy and mechanisms of tumor resistance in malignant glioma. J Oncol 2010;2010:251231
22. Nagy JA, Benjamin L, Zeng H, et al. Vascular permeability, vascular hyperpermeability and angiogenesis. Angiogenesis 2008;11(2):109-19
23. Jain RK. Molecular regulation of vessel maturation. Nat Med 2003;9(6):685-93 (Pubitemid 36749217)
24. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005;23(5):1011-27 (Pubitemid 46202320)
25. Autiero M, Luttun A, Tjwa M, Carmeliet P. Placental growth factor and its receptor, vascular endothelial growth factor receptor-1: novel targets for stimulation of ischemic tissue revascularization and inhibition of angiogenic and inflammatory disorders. J Thromb Haemost 2003;1(7):1356-70
26. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9(6):669-76 (Pubitemid 36749215)
27. Yonemura Y, Fushida S, Bando E, et al. Lymphangiogenesis and the vascular endothelial growth factor receptor (VEGFR)-3 in gastric cancer. Eur J Cancer 2001;37(7):918-23 (Pubitemid 32323971)
28. Bruce D, Tan PH. Blocking the interaction of vascular endothelial growth factor receptors with their ligands and their effector signaling as a novel therapeutic target for cancer: time for a new look? Expert Opin Investig Drugs 2011;20(10):1413-34
29. Anderson JC, McFarland BC, Gladson CL. New molecular targets in angiogenic vessels of glioblastoma tumours. Expert Rev Mol Med 2008;10:e23
30. Koch S, Tugues S, Li X, et al. Signal transduction by vascular endothelial growth factor receptors. Biochem J 2011;437(2):169-83
31. Nomura M, Yamagishi S, Harada S, et al. Possible participation of autocrine and paracrine vascular endothelial growth factors in hypoxia-induced proliferation of endothelial cells and pericytes. J Biol Chem 1995;270(47):28316-24
32. Ohgaki H, Kleihues P. Genetic pathways to primary and secondary glioblastoma. Am J Pathol 2007;170(5):1445-53 (Pubitemid 47339290)
33. Karcher S, Steiner HH, Ahmadi R, et al. Different angiogenic phenotypes in primary and secondary glioblastomas. Int J Cancer 2006;118(9):2182-9
34. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature 2011;473(7347):298-307
35. Bergers G, Song S. The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol 2005;7(4):452-64 (Pubitemid 41555617)
36. Maisonpierre PC, Suri C, Jones PF, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997;277(5322):55-60 (Pubitemid 27450643)
37. Holash J, Maisonpierre PC, Compton D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 1999;284(5422):1994-8 (Pubitemid 29309448)
38. Zagzag D, Amirnovin R, Greco MA, et al. Vascular apoptosis and involution in gliomas precede neovascularization: a novel concept for glioma growth and angiogenesis. Lab Invest 2000;80(6):837-49 (Pubitemid 30421801)
39. Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 2004;10(8):858-64 (Pubitemid 39070860)
40. Calabrese C, Poppleton H, Kocak M, et al. A perivascular niche for brain tumor stem cells. Cancer Cell 2007;11(1):69-82 (Pubitemid 46054518)
41. Shen Q, Wang Y, Kokovay E, et al. Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell 2008;3(3):289-300
42. Charles NA, Holland EC, Gilbertson R, et al. The brain tumor microenvironment. Glia 2011;59(8):1169-80
43. Yu SP, Yang XJ, Zhang B, et al. Enhanced invasion in vitro and the distribution patterns in vivo of CD133+ glioma stem cells. Chin Med J (Engl) 2011;124(17):2599-604
44. Cheng L, Wu Q, Guryanova OA, et al. Elevated invasive potential of glioblastoma stem cells. Biochem Biophys Res Commun 2011;406(4):643-8
45. Zhao Y, Dong J, Huang Q, et al. Endothelial cell transdifferentiation of human glioma stem progenitor cells in vitro. Brain Res Bull 2010;82(5-6):308-12
46. Wang R, Chadalavada K, Wilshire J, et al. Glioblastoma stem-like cells give rise to tumour endothelium. Nature 2010;468(7325):829-33
47. Ricci-Vitiani L, Pallini R, Biffoni M, et al. Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature 2010;468(7325):824-8
48. Folkman J. Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 2007;6(4):273-86 (Pubitemid 46505878)
49. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005;307(5706):58-62 (Pubitemid 40093472)
50. Stark-Vance V. Bevacizumab. and CPT-11 in the treatment of relapsed malignant glioma. Neuro-Oncology 2005;7:369
51. Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2009;27(28):4733-40
52. Kreisl TN, Kim L, Moore K, et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 2009;27(5):740-5
53. Cloughesy T. FDA accelerated approval benefits glioblastoma. Lancet Oncol 2010;11(12):1120
54. Drappatz J, Lee EQ, Hammond S, et al. Phase I study of panobinostat in combination with bevacizumab for recurrent high-grade glioma. J Neurooncol 2012;107(1):133-8
55. Raizer JJ, Grimm S, Chamberlain MC, et al. A phase 2 trial of single-agent bevacizumab given in an every-3-week schedule for patients with recurrent high-grade gliomas. Cancer 2010;116(22):5297-305
56. Vredenburgh JJ, Desjardins A, Herndon JE II, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 2007;25(30):4722-9 (Pubitemid 350086473)
57. Sathornsumetee S, Desjardins A, Vredenburgh JJ, et al. Phase II trial of bevacizumab and erlotinib in patients with recurrent malignant glioma. Neuro Oncol 2010;12(12):1300-10
58. Hasselbalch B, Lassen U, Hansen S, et al. Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide: a phase II trial. Neuro Oncol 2010;12(5):508-16
59. Desjardins A, Reardon DA, Coan A, et al. Bevacizumab and daily temozolomide for recurrent glioblastoma. Cancer 2012;118(5):1302-12
60. Reardon DA, Desjardins A, Peters KB, et al. Phase II study of carboplatin, irinotecan, and bevacizumab for bevacizumab naive, recurrent glioblastoma. J Neurooncol 2012;107(1):155-64
61. Reardon DA, Desjardins A, Peters KB, et al. Phase 2 study of carboplatin, irinotecan, and bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy. Cancer 2011;117(23):5351-8
62. Lai A, Tran A, Nghiemphu PL, et al. Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. J Clin Oncol 2011;29(2):142-8
63. Vredenburgh JJ, Desjardins A, Kirkpatrick JP, et al. Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme. Int J Radiat Oncol Biol Phys 2012;82(1):58-66
64. Gomez-Manzano C, Holash J, Fueyo J, et al. VEGF Trap induces antiglioma effect at different stages of disease. Neuro Oncol 2008;10(6):940-5
65. de Groot JF, Lamborn KR, Chang SM, et al. Phase II study of aflibercept in recurrent malignant glioma: a North American Brain Tumor Consortium study. J Clin Oncol 2011;29(19):2689-95
66. Batchelor TT, Duda DG, di Tomaso E, et al. Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. J Clin Oncol 2010;28(17):2817-23
67. Ahluwalia MS. 2010 Society for Neuro-Oncology Annual Meeting: a report of selected studies. Expert Rev Anticancer Ther 2011;11(2):161-3
68. Batchelor T MP, Neyns B, et al. The efficacy of cediranib as monotherapy and in combination with lomustine compared to lomustine alone in patients with recurrent glioblastoma: a phase III randomized study [abstract OT-25]. Neuro Oncol 2010;12(suppl 4):iv69-78
69. Chi AS, Gerstner ER, Eichler AF, et al. Phase Ib study of cediranib in combination with daily temozolomide and radiation in patients with newly diagnosed glioblastoma. ASCO Meeting Abstr 2009;27(15S):e13010
70. Adams VR, Leggas M. Sunitinib malate for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors. Clin Ther 2007;29(7):1338-53 (Pubitemid 47348120)
71. Neyns B, Sadones J, Chaskis C, et al. Phase II study of sunitinib malate in patients with recurrent high-grade glioma. J Neurooncol 2011;103(3):491-501
72. Reardon DA, Vredenburgh JJ, Coan A, et al. Phase I study of sunitinib and irinotecan for patients with recurrent malignant glioma. J Neurooncol 2011;105(3):621-7
73. Reardon DA, Vredenburgh JJ, Desjardins A, et al. Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma. J Neurooncol 2011;101(1):57-66
74. Jaeckle KA, Schiff D, Anderson SK, et al. NCCTG N0572 phase I/II trial of sorafenib and temsirolimus in patients with recurrent glioblastoma: A North Central Cancer Treatment Group study. ASCO Meeting Abstr 2011;29(15 suppl):2033
75. Hainsworth JD, Ervin T, Friedman E, et al. Concurrent radiotherapy and temozolomide followed by temozolomide and sorafenib in the first-line treatment of patients with glioblastoma multiforme. Cancer 2010;116(15):3663-9
76. Wood JM, Bold G, Buchdunger E, et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res 2000;60(8):2178-89 (Pubitemid 30225181)
77. Reardon D FH, Yung WKA, Brada M, et al. A phase I/II trial of PTK787/ZK 222584 (PTK/ZK), a novel, oral angiogenesis inhibitor, in combination with either temozolomide or lomustine for patients with recurrent glioblastoma multiforme (GBM). Proc Am Soc Clin Oncol 2004;22(14s):110s
78. Frederick B, Gustafson D, Bianco C, et al. ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinase activity in combination with radiotherapy. Int J Radiat Oncol Biol Phys 2006;64(1):33-7 (Pubitemid 41831206)
79. Drappatz J, Norden AD,Wong ET, et al. Phase I study of vandetanib with radiotherapy and temozolomide for newly diagnosed glioblastoma. Int J Radiat Oncol Biol Phys 2010;78(1):85-90
80. Spratlin J. Ramucirumab (IMC-1121B): monoclonal antibody inhibition of vascular endothelial growth factor receptor-2. Curr Oncol Rep 2011;13(2):97-102
81. Spratlin JL, Cohen RB, Eadens M, et al. Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol 2010;28(5):780-7
82. Zhang Y, Guessous F, Kofman A, et al. XL-184, a MET, VEGFR-2 and RET kinase inhibitor for the treatment of thyroid cancer, glioblastoma multiforme and NSCLC. IDrugs 2010;13(2):112-21
83. Wen PY, Prados M, Schiff D, et al. Phase II study of XL184 (BMS 907351), an inhibitor of MET, VEGFR2, and RET, in patients (pts) with progressive glioblastoma (GB). ASCO Meeting Abstr 2010;28(15 suppl):2006
84. Reardon DA, Cloughesy T, Rich J, et al. Pharmacokinetic drug interaction between AEE788 and RAD001 causing thrombocytopenia in patients with glioblastoma. Cancer Chemother Pharmacol 2012;69(1):281-7
85. Iwamoto FM, Lamborn KR, Robins HI, et al. Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02). Neuro Oncol 2010;12(8):855-61
86. Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 1990;8(7):1277-80 (Pubitemid 20195640)
87. van den Bent MJ, Vogelbaum MA, Wen PY, et al. End point assessment in gliomas: novel treatments limit usefulness of classical Macdonald's Criteria. J Clin Oncol 2009;27(18):2905-8
88. Norden AD, Young GS, Setayesh K, et al. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology 2008;70(10):779-87
89. Zuniga RM, Torcuator R, Jain R, et al. Efficacy, safety and patterns of response and recurrence in patients with recurrent high-grade gliomas treated with bevacizumab plus irinotecan. J Neurooncol 2009;91(3):329-36
90. Wen PY, Macdonald DR, Reardon DA, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 2010;28(11):1963-72
91. Sawlani RN, Raizer J, Horowitz SW, et al. Glioblastoma: a method for predicting response to antiangiogenic chemotherapy by using MR perfusion imaging-pilot study. Radiology 2010;255(2):622-8
92. Sorensen AG, Batchelor TT, Zhang WT, et al. A "vascular normalization index" as potential mechanistic biomarker to predict survival after a single dose of cediranib in recurrent glioblastoma patients. Cancer Res 2009;69(13):5296-300
93. Ellingson BM, Malkin MG, Rand SD, et al. Volumetric analysis of functional diffusion maps is a predictive imaging biomarker for cytotoxic and anti-angiogenic treatments in malignant gliomas. J Neurooncol 2011;102(1):95-103
94. Barajas RF Jr, Chang JS, Segal MR, et al. Differentiation of recurrent glioblastoma multiforme from radiation necrosis after external beam radiation therapy with dynamic susceptibility-weighted contrastenhanced perfusion MR imaging. Radiology 2009;253(2):486-96
95. 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):4714-21 (Pubitemid 350086472)
96. Takano S, Mashiko R, Osuka S, et al. Detection of failure of bevacizumab treatment for malignant glioma based on urinary matrix metalloproteinase activity. Brain Tumor Pathol 2010;27(2):89-94
97. Gerstner ER, Eichler AF, Plotkin SR, et al. Phase I trial with biomarker studies of vatalanib (PTK787) in patients with newly diagnosed glioblastoma treated with enzyme inducing anti-epileptic drugs and standard radiation and temozolomide. J Neurooncol 2011;103(2):325-32
98. Hasselbalch B, Eriksen JG, Broholm H, et al. Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan. APMIS 2010;118(8):585-94
99. Lucio-Eterovic AK, Piao Y, de Groot JF. Mediators of glioblastoma resistance and invasion during antivascular endothelial growth factor therapy. Clin Cancer Res 2009;15(14):4589-99
100. Ebos JM, Lee CR, Christensen JG, et al. Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy. Proc Natl Acad Sci USA 2007;104(43):17069-74 (Pubitemid 350210993)
101. 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 (Pubitemid 46075199)
102. Du R, Lu KV, Petritsch C, et al. HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell 2008;13(3):206-20 (Pubitemid 351318372)
103. Norden AD, Drappatz J,Wen PY. Antiangiogenic therapies for high-grade glioma. Nat Rev Neurol 2009;5(11):610-20
104. Bergers G, Song S, Meyer-Morse N, et al. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest 2003;111(9):1287-95 (Pubitemid 36554699)
105. Franco M, Paez-Ribes M, Cortez E, et al. Use of a Mouse Model of Pancreatic Neuroendocrine Tumors to Find Pericyte Biomarkers of Resistance to Anti-angiogenic Therapy. Horm Metab Res 2011;43(12):884-9
106. 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):306-14
107. Takano S. Glioblastoma angiogenesis: VEGF resistance solutions and new strategies based on molecular mechanisms of tumor vessel formation. Brain Tumor Pathol 2012;29(2):73-86
108. Rapisarda A, Melillo G. Overcoming disappointing results with antiangiogenic therapy by targeting hypoxia. Nat Rev Clin Oncol 2012;9(7):378-90
109. Moreno Garcia V, Basu B, Molife LR, Kaye SB. Combining Antiangiogenics to Overcome Resistance: rationale and clinical experience. Clin Cancer Res 2012;18(14):3750-61
110. 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):2335-42 (Pubitemid 38702844)
111. Wen PY, Cloughesy T, Kuhn J, et al. Phase I/II study of sorafenib and temsirolimus for patients with recurrent glioblastoma (GBM) (NABTC 05-02). ASCO Meeting Abstr 2009;27(15S):2006