The multifaceted activity of VEGF in angiogenesis - Implications for therapy responses

Cytokine and Growth Factor Reviews

Volumn 25, Issue 4, 2014, Pages 473-482

  Moens, Stijn ^a,b   Goveia, Jermaine ^a,b   Stapor, Peter C ^a,b   Cantelmo, Anna Rita ^a,b   Carmeliet, Peter ^a,b  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

Author keywords

Anti angiogenic therapy; Anti angiogenic therapy resistance; Cancer; Tumor microenvironment; Vascular endothelial growth factor

Indexed keywords

AFLIBERCEPT; AXITINIB; BEVACIZUMAB; PAZOPANIB; REGORAFENIB; SORAFENIB; SUNITINIB; VANDETANIB; VASCULOTROPIN; VASCULOTROPIN INHIBITOR; VASCULOTROPIN RECEPTOR; ANGIOGENESIS INHIBITOR; VASCULOTROPIN A; VEGFA PROTEIN, HUMAN;

ANTIANGIOGENIC THERAPY; BONE MARROW CELL; BREAST METASTASIS; CANCER CELL; CANCER CHEMOTHERAPY; DIFFERENTIATED THYROID CANCER; DRUG INDICATION; DRUG TARGETING; ENDOTHELIAL PROGENITOR CELL; ENDOTHELIUM CELL; EYE DISEASE; FIBROBLAST; GASTROINTESTINAL STROMAL TUMOR; GLIOBLASTOMA; HUMAN; KIDNEY CARCINOMA; KIDNEY METASTASIS; LIVER CELL CARCINOMA; MALIGNANT NEOPLASTIC DISEASE; METASTATIC COLORECTAL CANCER; NON SMALL CELL LUNG CANCER; NONHUMAN; OVARY CANCER; PANCREATIC NEUROENDOCRINE TUMOR; PERICYTE; SHORT SURVEY; SMOOTH MUSCLE FIBER; SOFT TISSUE SARCOMA; THYROID MEDULLARY CARCINOMA; TUMOR MICROENVIRONMENT; ANTAGONISTS AND INHIBITORS; CYTOLOGY; METABOLISM; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; SIGNAL TRANSDUCTION; VASCULARIZATION;

ANGIOGENESIS INHIBITORS; BONE MARROW CELLS; ENDOTHELIAL CELLS; FIBROBLASTS; HUMANS; MYELOID CELLS; MYOCYTES, SMOOTH MUSCLE; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; SIGNAL TRANSDUCTION; TUMOR MICROENVIRONMENT; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84907969444     PISSN: 13596101     EISSN: 18790305     Source Type: Journal    
DOI: 10.1016/j.cytogfr.2014.07.009     Document Type: Short Survey

References (136)

1. Welti J., Loges S., Dimmeler S., Carmeliet P. Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer. J Clin Invest 2013, 123:3190-3200.
2. Poon R.T., Fan S.T., Wong J. Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol 2001, 19:1207-1225.
3. Bottsford-Miller J.N., Coleman R.L., Sood A.K. Resistance and escape from antiangiogenesis therapy: clinical implications and future strategies. J Clin Oncol 2012, 30:4026-4034.
4. Sennino B., McDonald D.M. Controlling escape from angiogenesis inhibitors. Nat Rev Cancer 2012, 12:699-709.
5. Goel H.L., Mercurio A.M. VEGF targets the tumour cell. Nat Rev Cancer 2013, 13:871-882.
6. Shibuya M. Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases. J Biochem 2013, 153:13-19.
7. Lee S., Chen T.T., Barber C.L., Jordan M.C., Murdock J., Desai S., et al. Autocrine VEGF signaling is required for vascular homeostasis. Cell 2007, 130:691-703.
8. Vempati P., Popel A.S., Mac Gabhann F. Extracellular regulation of VEGF: isoforms, proteolysis, and vascular patterning. Cytokine Growth Factor Rev 2014, 25:1-19.
9. Fischer C., Mazzone M., Jonckx B., Carmeliet P. FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy. Nat Rev Cancer 2008, 8:942-956.
10. Zhang G.H., Qin R., Zhang S.H., Zhu H. Effects of vascular endothelial growth factor B on proliferation and migration in EA.Hy926 cells. Mol Biol Rep 2013, 41:779-785.
11. Carmeliet P., Jain R.K. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov 2011, 10:417-427.
12. Matsuda K., Ohga N., Hida Y., Muraki C., Tsuchiya K., Kurosu T., et al. Isolated tumor endothelial cells maintain specific character during long-term culture. Biochem Biophys Res Commun 2010, 394:947-954.
13. Taylor S.M., Nevis K.R., Park H.L., Rogers G.C., Rogers S.L., Cook J.G., et al. Angiogenic factor signaling regulates centrosome duplication in endothelial cells of developing blood vessels. Blood 2010, 116:3108-3117.
14. Nor J.E., Christensen J., Mooney D.J., Polverini P.J. Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl-2 expression. Am J Pathol 1999, 154:375-384.
15. Alon T., Hemo I., Itin A., Pe'er J., Stone J., Keshet E. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1995, 1:1024-1028.
16. Nagy J.A., Chang S.H., Shih S.C., Dvorak A.M., Dvorak H.F. Heterogeneity of the tumor vasculature. Semin Thromb Hemost 2010, 36:321-331.
17. Weis S., Cui J., Barnes L., Cheresh D. Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis. J Cell Biol 2004, 167:223-229.
18. Eliceiri B.P., Paul R., Schwartzberg P.L., Hood J.D., Leng J., Cheresh D.A. Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. Mol Cell 1999, 4:915-924.
19. Dejana E., Tournier-Lasserve E., Weinstein B.M. The control of vascular integrity by endothelial cell junctions: molecular basis and pathological implications. Dev Cell 2009, 16:209-221.
20. Sun Z., Li X., Massena S., Kutschera S., Padhan N., Gualandi L., et al. VEGFR2 induces c-Src signaling and vascular permeability in vivo via the adaptor protein TSAd. J Exp Med 2012, 209:1363-1377.
21. Hashimoto A., Hashimoto S., Ando R., Noda K., Ogawa E., Kotani H., et al. GEP100-Arf6-AMAP1-cortactin pathway frequently used in cancer invasion is activated by VEGFR2 to promote angiogenesis. PLoS ONE 2011, 6:e23359.
22. Phung T.L., Ziv K., Dabydeen D., Eyiah-Mensah G., Riveros M., Perruzzi C., et al. Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin. Cancer Cell 2006, 10:159-170.
23. Bentley K., Franco C.A., Philippides A., Blanco R., Dierkes M., Gebala V., et al. The role of differential VE-cadherin dynamics in cell rearrangement during angiogenesis. Nat Cell Biol 2014, 16:309-321.
24. Kim I., Moon S.O., Kim S.H., Kim H.J., Koh Y.S., Koh G.Y. Vascular endothelial growth factor expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin through nuclear factor-kappa B activation in endothelial cells. J Biol Chem 2001, 276:7614-7620.
25. Schlesinger M., Bendas G. Vascular cell adhesion molecule-1 (VCAM-1)-An increasing insight into its role in tumorigenicity and metastasis. Int J Cancer 2014.
26. De Bock K., Georgiadou M., Schoors S., Kuchnio A., Wong B.W., Cantelmo A.R., et al. Role of PFKFB3-driven glycolysis in vessel sprouting. Cell 2013, 154:651-663.
27. Schoors S., De Bock K., Cantelmo A.R., Georgiadou M., Ghesquiere B., Cauwenberghs S., et al. Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis. Cell Metab 2014, 19:37-48.
28. Xu Y., An X., Guo X., Habtetsion T.G., Wang Y., Xu X., et al. Endothelial 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase, isoform 3 plays a critical role in angiogenesis. Arteriosclerosis Thromb Vasc Biol 2014, 34:1231-1239.
29. Croci D.O., Cerliani J.P., Dalotto-Moreno T., Mendez-Huergo S.P., Mascanfroni I.D., Dergan-Dylon S., et al. Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors. Cell 2014, 156:744-758.
30. Kirschmann D.A., Seftor E.A., Hardy K.M., Seftor R.E., Hendrix M.J. Molecular pathways: vasculogenic mimicry in tumor cells: diagnostic and therapeutic implications. Clin Cancer Res 2012, 18:2726-2732.
31. Carmeliet P., Jain R.K. Molecular mechanisms and clinical applications of angiogenesis. Nature 2011, 473:298-307.
32. Cao Z., Bao M., Miele L., Sarkar F.H., Wang Z., Zhou Q. Tumour vasculogenic mimicry is associated with poor prognosis of human cancer patients: a systemic review and meta-analysis. Eur J Cancer 2013, 49:3914-3923.
33. Hlushchuk R., Riesterer O., Baum O., Wood J., Gruber G., Pruschy M., et al. Tumor recovery by angiogenic switch from sprouting to intussusceptive angiogenesis after treatment with PTK787/ZK222584 or ionizing radiation. Am J Pathol 2008, 173:1173-1185.
34. Hillen F., Griffioen A.W. Tumour vascularization: sprouting angiogenesis and beyond. Cancer Metastasis Rev 2007, 26:489-502.
35. Holash J., Maisonpierre P.C., Compton D., Boland P., Alexander C.R., Zagzag D., et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 1999, 284:1994-1998.
36. Nico B., Crivellato E., Guidolin D., Annese T., Longo V., Finato N., et al. Intussusceptive microvascular growth in human glioma. Clin Exp Med 2010, 10:93-98.
37. Yao X., Ping Y., Liu Y., Chen K., Yoshimura T., Liu M., et al. Vascular endothelial growth factor receptor 2 (VEGFR-2) plays a key role in vasculogenic mimicry formation, neovascularization and tumor initiation by Glioma stem-like cells. PLOS ONE 2013, 8:e57188.
38. Christiansen A., Detmar M. Lymphangiogenesis and cancer. Genes Cancer 2011, 2:1146-1158.
39. Stacker S.A., Williams S.P., Karnezis T., Shayan R., Fox S.B., Achen M.G. Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat Rev Cancer 2014, 14:159-172.
40. Kovacic J.C., Moore J., Herbert A., Ma D., Boehm M., Graham R.M. Endothelial progenitor cells, angioblasts, and angiogenesis - old terms reconsidered from a current perspective. Trends Cardiovasc Med 2008, 18:45-51.
41. Hattori K., Dias S., Heissig B., Hackett N.R., Lyden D., Tateno M., et al. Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med 2001, 193:1005-1014.
42. Lyden D., Hattori K., Dias S., Costa C., Blaikie P., Butros L., et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001, 7:1194-1201.
43. Grunewald M., Avraham I., Dor Y., Bachar-Lustig E., Itin A., Jung S., et al. VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell 2006, 124:175-189.
44. Avraham-Davidi I., Yona S., Grunewald M., Landsman L., Cochain C., Silvestre J.S., et al. On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells. J Exp Med 2013, 210:2611-2625.
45. Lu-Emerson C., Snuderl M., Kirkpatrick N.D., Goveia J., Davidson C., Huang Y., et al. Increase in tumor-associated macrophages after antiangiogenic therapy is associated with poor survival among patients with recurrent glioblastoma. Neurooncology 2013, 15:1079-1087.
46. Lin E.Y., Li J.F., Gnatovskiy L., Deng Y., Zhu L., Grzesik D.A., et al. Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res 2006, 66:11238-11246.
47. Rolny C., Mazzone M., Tugues S., Laoui D., Johansson I., Coulon C., et al. HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF. Cancer Cell 2011, 19:31-44.
48. Snuderl M., Batista A., Kirkpatrick N.D., Ruiz de Almodovar C., Riedemann L., Walsh E.C., et al. Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma. Cell 2013, 152:1065-1076.
49. Ferrara N. Role of myeloid cells in vascular endothelial growth factor-independent tumor angiogenesis. Curr Opin Hematol 2010, 17:219-224.
50. Welford A.F., Biziato D., Coffelt S.B., Nucera S., Fisher M., Pucci F., et al. TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice. J Clin Invest 2011, 121:1969-1973.
51. Venneri M.A., De Palma M., Ponzoni M., Pucci F., Scielzo C., Zonari E., et al. Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer. Blood 2007, 109:5276-5285.
52. De Palma M., Venneri M.A., Galli R., Sergi Sergi L., Politi L.S., Sampaolesi M., et al. Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 2005, 8:211-226.
53. Shojaei F., Wu X., Malik A.K., Zhong C., Baldwin M.E., Schanz S., et al. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol 2007, 25:911-920.
54. Panka D.J., Liu Q., Geissler A.K., Mier J.W. Effects of HDM2 antagonism on sunitinib resistance, p53 activation, SDF-1 induction, and tumor infiltration by CD11b+/Gr-1+ myeloid derived suppressor cells. Mol Cancer 2013, 12:17.
55. Dondossola E., Rangel R., Guzman-Rojas L., Barbu E.M., Hosoya H., St John L.S., et al. CD13-positive bone marrow-derived myeloid cells promote angiogenesis, tumor growth, and metastasis. Proc Natl Acad Sci USA 2013, 110:20717-20722.
56. Phan V.T., Wu X., Cheng J.H., Sheng R.X., Chung A.S., Zhuang G., et al. Oncogenic RAS pathway activation promotes resistance to anti-VEGF therapy through G-CSF-induced neutrophil recruitment. Proc Natl Acad Sci USA 2013, 110:6079-6084.
57. Chung A.S., Wu X., Zhuang G., Ngu H., Kasman I., Zhang J., et al. An interleukin-17-mediated paracrine network promotes tumor resistance to anti-angiogenic therapy. Nat Med 2013, 19:1114-1123.
58. Armulik A., Genove G., Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 2011, 21:193-215.
59. Cooke V.G., LeBleu V.S., Keskin D., Khan Z., O'Connell J.T., Teng Y., et al. Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway. Cancer Cell 2012, 21:66-81.
60. De Bock K., Mazzone M., Carmeliet P. Antiangiogenic therapy, hypoxia, and metastasis: risky liaisons, or not. Nat Rev Clin Oncol 2011, 8:393-404.
61. Huang H., Bhat A., Woodnutt G., Lappe R. Targeting the ANGPT-TIE2 pathway in malignancy. Nat Rev Cancer 2010, 10:575-585.
62. Lobov I.B., Brooks P.C., Lang R.A. Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc Natl Acad Sci USA 2002, 99:11205-11210.
63. Banerjee S., Mehta S., Haque I., Sengupta K., Dhar K., Kambhampati S., et al. VEGF-A165 induces human aortic smooth muscle cell migration by activating neuropilin-1-VEGFR1-PI3K axis. Biochemistry 2008, 47:3345-3351.
64. Wang H., Keiser J.A. Vascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle cells: role of flt-1. Circ Res 1998, 83:832-840.
65. Franco M., Roswall P., Cortez E., Hanahan D., Pietras K. Pericytes promote endothelial cell survival through induction of autocrine VEGF-A signaling and Bcl-w expression. Blood 2011, 118:2906-2917.
66. Mancuso M.R., Davis R., Norberg S.M., O'Brien S., Sennino B., Nakahara T., et al. Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J Clin Invest 2006, 116:2610-2621.
67. Erber R., Thurnher A., Katsen A.D., Groth G., Kerger H., Hammes H.P., et al. Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J 2004, 18:338-340.
68. Hosaka K., Yang Y., Seki T., Nakamura M., Andersson P., Rouhi P., et al. Tumour PDGF-BB expression levels determine dual effects of anti-PDGF drugs on vascular remodelling and metastasis. Nat Commun 2013, 4:2129.
69. Hainsworth J.D., Spigel D.R., Sosman J.A., Burris H.A., Farley C., Cucullu H., et al. Treatment of advanced renal cell carcinoma with the combination bevacizumab/erlotinib/imatinib: a phase I/II trial. Clin Genitourin Cancer 2007, 5:427-432.
70. Guan Y.Y., Luan X., Xu J.R., Liu Y.R., Lu Q., Wang C., et al. Selective eradication of tumor vascular pericytes by peptide-conjugated nanoparticles for antiangiogenic therapy of melanoma lung metastasis. Biomaterials 2014, 35:3060-3070.
71. Dong J., Grunstein J., Tejada M., Peale F., Frantz G., Liang W.C., et al. VEGF-null cells require PDGFR alpha signaling-mediated stromal fibroblast recruitment for tumorigenesis. EMBO J 2004, 23:2800-2810.
72. Jin X., Ge X., Zhu D.L., Yan C., Chu Y.F., Chen W.D., et al. Expression and function of vascular endothelial growth factor receptors (Flt-1 and Flk-1) in vascular adventitial fibroblasts. J Mol Cell Cardiol 2007, 43:292-300.
73. Berthaut A., Mirshahi P., Benabbou N., Azzazene D., Bordu C., Therwath A., et al. Vascular endothelial growth factor receptor-1 (VEGFR-1) expression in human corneal fibroblast decreased with age. Mol Vis 2009, 15:1997-2007.
74. Larsen M., Artym V.V., Green J.A., Yamada K.M. The matrix reorganized: extracellular matrix remodeling and integrin signaling. Curr Opin Cell Biol 2006, 18:463-471.
75. Lee S., Jilani S.M., Nikolova G.V., Carpizo D., Iruela-Arispe M.L. Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. J Cell Biol 2005, 169:681-691.
76. Davis G.E., Senger D.R. Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ Res 2005, 97:1093-1107.
77. Abraham S., Riggs M.J., Nelson K., Lee V., Rao R.R. Characterization of human fibroblast-derived extracellular matrix components for human pluripotent stem cell propagation. Acta Biomater 2010, 6:4622-4633.
78. Kalluri R., Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer 2006, 6:392-401.
79. Yaqoob U., Cao S., Shergill U., Jagavelu K., Geng Z., Yin M., et al. Neuropilin-1 stimulates tumor growth by increasing fibronectin fibril assembly in the tumor microenvironment. Cancer Res 2012, 72:4047-4059.
80. Orimo A., Gupta P.B., Sgroi D.C., Arenzana-Seisdedos F., Delaunay T., Naeem R., et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 2005, 121:335-348.
81. Crawford Y., Kasman I., Yu L., Zhong C., Wu X., Modrusan Z., et al. PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. Cancer Cell 2009, 15:21-34.
82. Shojaei F., Lee J.H., Simmons B.H., Wong A., Esparza C.O., Plumlee P.A., et al. HGF/c-Met acts as an alternative angiogenic pathway in sunitinib-resistant tumors. Cancer Res 2010, 70:10090-10100.
83. Li D., Xie K., Ding G., Li J., Chen K., Li H., et al. Tumor resistance to anti-VEGF therapy through up-regulation of VEGF-C expression. Cancer Lett 2014, 346:45-52.
84. Lieu C.H., Tran H., Jiang Z.Q., Mao M., Overman M.J., Lin E., et al. The association of alternate VEGF ligands with resistance to anti-VEGF therapy in metastatic colorectal cancer. PLOS ONE 2013, 8:e77117.
85. Hwang J.E., Lee J.H., Park M.R., Kim D.E., Bae W.K., Shim H.J., et al. Blockade of VEGFR-1 and VEGFR-2 enhances paclitaxel sensitivity in gastric cancer cells. Yonsei Med J 2013, 54:374-380.
86. Liang Y., Brekken R.A., Hyder S.M. Vascular endothelial growth factor induces proliferation of breast cancer cells and inhibits the anti-proliferative activity of anti-hormones. Endocr Relat Cancer 2006, 13:905-919.
87. Perrot-Applanat M., Di Benedetto M. Autocrine functions of VEGF in breast tumor cells: adhesion, survival, migration and invasion. Cell Adhes Migr 2012, 6:547-553.
88. Casanova M.L., Larcher F., Casanova B., Murillas R., Fernandez-Acenero M.J., Villanueva C., et al. A critical role for ras-mediated, epidermal growth factor receptor-dependent angiogenesis in mouse skin carcinogenesis. Cancer Res 2002, 62:3402-3407.
89. Goel H.L., Pursell B., Standley C., Fogarty K., Mercurio A.M. Neuropilin-2 regulates alpha6beta1 integrin in the formation of focal adhesions and signaling. J Cell Sci 2012, 125:497-506.
90. Lu K.V., Chang J.P., Parachoniak C.A., Pandika M.M., Aghi M.K., Meyronet D., et al. VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex. Cancer Cell 2012, 22:21-35.
91. Xu Y., Li Q., Li X.Y., Yang Q.Y., Xu W.W., Liu G.L. Short-term anti-vascular endothelial growth factor treatment elicits vasculogenic mimicry formation of tumors to accelerate metastasis. J Exp Clin Cancer Res 2012, 31:16.
92. Schoenfeld J.D., Dranoff G. Anti-angiogenesis immunotherapy. Hum Vaccin 2011, 7:976-981.
93. Kandalaft L.E., Chiang C.L., Tanyi J., Motz G., Balint K., Mick R., et al. A phase I vaccine trial using dendritic cells pulsed with autologous oxidized lysate for recurrent ovarian cancer. J Transl Med 2013, 11:149.
94. Huang Y., Yuan J., Righi E., Kamoun W.S., Ancukiewicz M., Nezivar J., et al. Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc Natl Acad Sci USA 2012, 109:17561-17566.
95. Akerley W., Boucher K., Rich N., Egbert L., Harker G., Bylund J., et al. A phase II study of bevacizumab and erlotinib as initial treatment for metastatic non-squamous, non-small cell lung cancer with serum proteomic evaluation. Lung Cancer 2013, 79:307-311.
96. Miles D.W., de Haas S.L., Dirix L.Y., Romieu G., Chan A., Pivot X., et al. Biomarker results from the AVADO phase 3 trial of first-line bevacizumab plus docetaxel for HER2-negative metastatic breast cancer. Br J Cancer 2013, 108:1052-1060.
97. Van Cutsem E., de Haas S., Kang Y.K., Ohtsu A., Tebbutt N.C., Ming Xu J., et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol 2012, 30:2119-2127.
98. Liu Y., Starr M.D., Bulusu A., Pang H., Wong N.S., Honeycutt W., et al. Correlation of angiogenic biomarker signatures with clinical outcomes in metastatic colorectal cancer patients receiving capecitabine, oxaliplatin, and bevacizumab. Cancer Med 2013, 2:234-242.
99. Lambrechts D., Claes B., Delmar P., Reumers J., Mazzone M., Yesilyurt B.T., et al. VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials. Lancet Oncol 2012, 13:724-733.
100. Penn J.S., Madan A., Caldwell R.B., Bartoli M., Caldwell R.W., Hartnett M.E. Vascular endothelial growth factor in eye disease. Prog Retin Eye Res 2008, 27:331-371.
101. Pe'er J., Shweiki D., Itin A., Hemo I., Gnessin H., Keshet E. Hypoxia-induced expression of vascular endothelial growth factor by retinal cells is a common factor in neovascularizing ocular diseases. Lab Invest 1995, 72:638-645.
102. Tolentino M.J., Miller J.W., Gragoudas E.S., Chatzistefanou K., Ferrara N., Adamis A.P. Vascular endothelial growth factor is sufficient to produce iris neovascularization and neovascular glaucoma in a nonhuman primate. Arch Ophthalmol 1996, 114:964-970.
103. Rasmussen A., Sander B. Long-term longitudinal study of patients treated with ranibizumab for neovascular age-related macular degeneration. Curr Opin Ophthalmol 2014, 25:158-163.
104. van Lookeren Campagne M., LeCouter J., Yaspan B.L., Ye W. Mechanisms of age-related macular degeneration and therapeutic opportunities. J Pathol 2014, 232:151-164.
105. Miller J.W., Adamis A.P., Aiello L.P. Vascular endothelial growth factor in ocular neovascularization and proliferative diabetic retinopathy. Diab Metab Rev 1997, 13:37-50.
106. Stone J., Chan-Ling T., Pe'er J., Itin A., Gnessin H., Keshet E. Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity. Invest Ophthalmol Vis Sci 1996, 37:290-299.
107. Pierce E.A., Avery R.L., Foley E.D., Aiello L.P., Smith L.E. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc Natl Acad Sci USA 1995, 92:905-909.
108. Aiello L.P., Northrup J.M., Keyt B.A., Takagi H., Iwamoto M.A. Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch Ophthalmol 1995, 113:1538-1544.
109. Liu J., Copland D.A., Horie S., Wu W.K., Chen M., Xu Y., et al. Myeloid cells expressing VEGF and arginase-1 following uptake of damaged retinal pigment epithelium suggests potential mechanism that drives the onset of choroidal angiogenesis in mice. PLOS ONE 2013, 8:e72935.
110. Cao X., Shen D., Patel M.M., Tuo J., Johnson T.M., Olsen T.W., et al. Macrophage polarization in the maculae of age-related macular degeneration: a pilot study. Pathol Int 2011, 61:528-535.
111. Brown D.M., Michels M., Kaiser P.K., Heier J.S., Sy J.P., Ianchulev T. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmology 2009, 116:57-65. e5.
112. Krispel C., Rodrigues M., Xin X., Sodhi A. Ranibizumab in diabetic macular edema. World J Diab 2013, 4:310-318.
113. van der Reis M.I., La Heij E.C., De Jong-Hesse Y., Ringens P.J., Hendrikse F., Schouten J.S. A systematic review of the adverse events of intravitreal anti-vascular endothelial growth factor injections. Retina 2011, 31:1449-1469.
114. Semeraro F., Morescalchi F., Duse S., Parmeggiani F., Gambicorti E., Costagliola C. Aflibercept in wet AMD: specific role and optimal use. Drug Des Dev Ther 2013, 7:711-722.
115. Stewart M.W., Rosenfeld P.J., Penha F.M., Wang F., Yehoshua Z., Bueno-Lopez E., et al. Pharmacokinetic rationale for dosing every 2 weeks versus 4 weeks with intravitreal ranibizumab, bevacizumab, and aflibercept (vascular endothelial growth factor trap-eye). Retina 2012, 32:434-457.
116. Heier J.S., Brown D.M., Chong V., Korobelnik J.F., Kaiser P.K., Nguyen Q.D., et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 2012, 119:2537-2548.
117. Hurwitz H., Fehrenbacher L., Novotny W., Cartwright T., Hainsworth J., Heim W., et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004, 350:2335-2342.
118. Sandler A., Gray R., Perry M.C., Brahmer J., Schiller J.H., Dowlati A., et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006, 355:2542-2550.
119. Friedman H.S., Prados M.D., Wen P.Y., Mikkelsen T., Schiff D., Abrey L.E., et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2009, 27:4733-4740.
120. Escudier B., Bellmunt J., Negrier S., Bajetta E., Melichar B., Bracarda S., et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol 2010, 28:2144-2150.
121. Perren T.J., Swart A.M., Pfisterer J., Ledermann J.A., Pujade-Lauraine E., Kristensen G., et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 2011, 365:2484-2496.
122. Miller K., Wang M., Gralow J., Dickler M., Cobleigh M., Perez E.A., et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007, 357:2666-2676.
123. Ramlau R., Gorbunova V., Ciuleanu T.E., Novello S., Ozguroglu M., Goksel T., et al. Aflibercept and docetaxel versus docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial. J Clin Oncol 2012, 30:3640-3647.
124. Van Cutsem E., Tabernero J., Lakomy R., Prenen H., Prausova J., Macarulla T., et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 2012, 30:3499-3506.
125. Raymond E., Dahan L., Raoul J.L., Bang Y.J., Borbath I., Lombard-Bohas C., et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 2011, 364:501-513.
126. Motzer R.J., Michaelson M.D., Rosenberg J., Bukowski R.M., Curti B.D., George D.J., et al. Sunitinib efficacy against advanced renal cell carcinoma. J Urol 2007, 178:1883-1887.
127. Demetri G.D., van Oosterom A.T., Garrett C.R., Blackstein M.E., Shah M.H., Verweij J., et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006, 368:1329-1338.
128. Llovet J.M., Ricci S., Mazzaferro V., Hilgard P., Gane E., Blanc J.F., et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008, 359:378-390.
129. Brose M.S., Nutting C.M., Sherman S.I., Shong Y.K., Smit J.W., Reike G., et al. Rationale and design of decision: a double-blind, randomized, placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory, differentiated thyroid cancer. BMC Cancer 2011, 11:349.
130. Escudier B., Eisen T., Stadler W.M., Szczylik C., Oudard S., Siebels M., et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007, 356:125-134.
131. Sternberg C.N., Hawkins R.E., Wagstaff J., Salman P., Mardiak J., Barrios C.H., et al. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer 2013, 49:1287-1296.
132. van der Graaf W.T., Blay J.Y., Chawla S.P., Kim D.W., Bui-Nguyen B., Casali P.G., et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2012, 379:1879-1886.
133. Wells S.A., Robinson B.G., Gagel R.F., Dralle H., Fagin J.A., Santoro M., et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 2012, 30:134-141.
134. Grothey A., Van Cutsem E., Sobrero A., Siena S., Falcone A., Ychou M., et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013, 381:303-312.
135. Demetri G.D., Reichardt P., Kang Y.K., Blay J.Y., Rutkowski P., Gelderblom H., et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013, 381:295-302.
136. Motzer R.J., Escudier B., Tomczak P., Hutson T.E., Michaelson M.D., Negrier S., et al. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol 2013, 14:552-562.