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Published in: Angiogenesis 4/2017

01-11-2017 | Review Paper

Tumor angiogenesis and vascular normalization: alternative therapeutic targets

Authors: Claire Viallard, Bruno Larrivée

Published in: Angiogenesis | Issue 4/2017

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Abstract

Tumor blood vessels are a key target for cancer therapeutic management. Tumor cells secrete high levels of pro-angiogenic factors which contribute to the creation of an abnormal vascular network characterized by disorganized, immature and permeable blood vessels, resulting in poorly perfused tumors. The hypoxic microenvironment created by impaired tumor perfusion can promote the selection of more invasive and aggressive tumor cells and can also impede the tumor-killing action of immune cells. Furthermore, abnormal tumor perfusion also reduces the diffusion of chemotherapeutic drugs and radiotherapy efficiency. To fight against this defective phenotype, the normalization of the tumor vasculature has emerged as a new therapeutic strategy. Vascular normalization, by restoring proper tumor perfusion and oxygenation, could limit tumor cell invasiveness and improve the effectiveness of anticancer treatments. In this review, we investigate the mechanisms involved in tumor angiogenesis and describe strategies used to achieve vascular normalization.
Literature
11.
go back to reference Jakobsson L, Franco CA, Bentley K et al (2010) Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting. Nat Cell Biol 12:943–953. doi:10.1038/ncb2103 PubMedCrossRef Jakobsson L, Franco CA, Bentley K et al (2010) Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting. Nat Cell Biol 12:943–953. doi:10.​1038/​ncb2103 PubMedCrossRef
23.
go back to reference Davis GE, Bayless KJ (2003) An integrin and Rho GTPase-dependent pinocytic vacuole mechanism controls capillary lumen formation in collagen and fibrin matrices. Microcirc NY N 10:27–44. doi:10.1038/sj.mn.7800175 CrossRef Davis GE, Bayless KJ (2003) An integrin and Rho GTPase-dependent pinocytic vacuole mechanism controls capillary lumen formation in collagen and fibrin matrices. Microcirc NY N 10:27–44. doi:10.​1038/​sj.​mn.​7800175 CrossRef
24.
go back to reference Davis GE, Koh W, Stratman AN (2007) Mechanisms controlling human endothelial lumen formation and tube assembly in three-dimensional extracellular matrices. Birth Defects Res Part C Embryo Today Rev 81:270–285. doi:10.1002/bdrc.20107 CrossRef Davis GE, Koh W, Stratman AN (2007) Mechanisms controlling human endothelial lumen formation and tube assembly in three-dimensional extracellular matrices. Birth Defects Res Part C Embryo Today Rev 81:270–285. doi:10.​1002/​bdrc.​20107 CrossRef
25.
go back to reference Sacharidou A, Stratman AN, Davis GE (2012) Molecular mechanisms controlling vascular lumen formation in three-dimensional extracellular matrices. Cells Tissues Organs 195:122–143. doi:10.1159/000331410 PubMedCrossRef Sacharidou A, Stratman AN, Davis GE (2012) Molecular mechanisms controlling vascular lumen formation in three-dimensional extracellular matrices. Cells Tissues Organs 195:122–143. doi:10.​1159/​000331410 PubMedCrossRef
28.
go back to reference Augustin HG, Koh GY, Thurston G, Alitalo K (2009) Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol 10:165–177. doi:10.1038/nrm2639 PubMedCrossRef Augustin HG, Koh GY, Thurston G, Alitalo K (2009) Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol 10:165–177. doi:10.​1038/​nrm2639 PubMedCrossRef
30.
49.
go back to reference Marín-Hernández A, Gallardo-Pérez JC, Ralph SJ et al (2009) HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini Rev Med Chem 9:1084–1101PubMedCrossRef Marín-Hernández A, Gallardo-Pérez JC, Ralph SJ et al (2009) HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini Rev Med Chem 9:1084–1101PubMedCrossRef
53.
go back to reference Larcher F, Franco M, Bolontrade M et al (2003) Modulation of the angiogenesis response through Ha-ras control, placenta growth factor, and angiopoietin expression in mouse skin carcinogenesis. Mol Carcinog 37:83–90. doi:10.1002/mc.10126 PubMedCrossRef Larcher F, Franco M, Bolontrade M et al (2003) Modulation of the angiogenesis response through Ha-ras control, placenta growth factor, and angiopoietin expression in mouse skin carcinogenesis. Mol Carcinog 37:83–90. doi:10.​1002/​mc.​10126 PubMedCrossRef
55.
go back to reference Arbiser JL, Moses MA, Fernandez CA et al (1997) Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways. Proc Natl Acad Sci USA 94:861–866PubMedPubMedCentralCrossRef Arbiser JL, Moses MA, Fernandez CA et al (1997) Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways. Proc Natl Acad Sci USA 94:861–866PubMedPubMedCentralCrossRef
56.
go back to reference Govindarajan B, Bai X, Cohen C et al (2003) Malignant transformation of melanocytes to melanoma by constitutive activation of mitogen-activated protein kinase kinase (MAPKK) signaling. J Biol Chem 278:9790–9795. doi:10.1074/jbc.M212929200 PubMedCrossRef Govindarajan B, Bai X, Cohen C et al (2003) Malignant transformation of melanocytes to melanoma by constitutive activation of mitogen-activated protein kinase kinase (MAPKK) signaling. J Biol Chem 278:9790–9795. doi:10.​1074/​jbc.​M212929200 PubMedCrossRef
61.
go back to reference Ribatti D, Nico B, Floris C et al (2005) Microvascular density, vascular endothelial growth factor immunoreactivity in tumor cells, vessel diameter and intussusceptive microvascular growth in primary melanoma. Oncol Rep 14:81–84PubMed Ribatti D, Nico B, Floris C et al (2005) Microvascular density, vascular endothelial growth factor immunoreactivity in tumor cells, vessel diameter and intussusceptive microvascular growth in primary melanoma. Oncol Rep 14:81–84PubMed
65.
go back to reference Ruf W, Seftor EA, Petrovan RJ et al (2003) Differential role of tissue factor pathway inhibitors 1 and 2 in melanoma vasculogenic mimicry. Cancer Res 63:5381–5389PubMed Ruf W, Seftor EA, Petrovan RJ et al (2003) Differential role of tissue factor pathway inhibitors 1 and 2 in melanoma vasculogenic mimicry. Cancer Res 63:5381–5389PubMed
68.
go back to reference Lyden D, Hattori K, Dias S et al (2001) Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 7:1194–1201. doi:10.1038/nm1101-1194 PubMedCrossRef Lyden D, Hattori K, Dias S et al (2001) Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 7:1194–1201. doi:10.​1038/​nm1101-1194 PubMedCrossRef
74.
go back to reference Wickersheim A, Kerber M, de Miguel LS et al (2009) Endothelial progenitor cells do not contribute to tumor endothelium in primary and metastatic tumors. Int J Cancer 125:1771–1777. doi:10.1002/ijc.24605 PubMedCrossRef Wickersheim A, Kerber M, de Miguel LS et al (2009) Endothelial progenitor cells do not contribute to tumor endothelium in primary and metastatic tumors. Int J Cancer 125:1771–1777. doi:10.​1002/​ijc.​24605 PubMedCrossRef
76.
go back to reference Larrivée B, Niessen K, Pollet I et al (2005) Minimal contribution of marrow-derived endothelial precursors to tumor vasculature. J Immunol Baltim Md 175:2890–2899 Larrivée B, Niessen K, Pollet I et al (2005) Minimal contribution of marrow-derived endothelial precursors to tumor vasculature. J Immunol Baltim Md 175:2890–2899
77.
go back to reference Machein MR, Renninger S, de Lima-Hahn E, Plate KH (2003) Minor contribution of bone marrow-derived endothelial progenitors to the vascularization of murine gliomas. Brain Pathol Zur Switz 13:582–597CrossRef Machein MR, Renninger S, de Lima-Hahn E, Plate KH (2003) Minor contribution of bone marrow-derived endothelial progenitors to the vascularization of murine gliomas. Brain Pathol Zur Switz 13:582–597CrossRef
78.
go back to reference Zentilin L, Tafuro S, Zacchigna S et al (2006) Bone marrow mononuclear cells are recruited to the sites of VEGF-induced neovascularization but are not incorporated into the newly formed vessels. Blood 107:3546–3554. doi:10.1182/blood-2005-08-3215 PubMedCrossRef Zentilin L, Tafuro S, Zacchigna S et al (2006) Bone marrow mononuclear cells are recruited to the sites of VEGF-induced neovascularization but are not incorporated into the newly formed vessels. Blood 107:3546–3554. doi:10.​1182/​blood-2005-08-3215 PubMedCrossRef
82.
go back to reference Busk M, Horsman MR (2013) Relevance of hypoxia in radiation oncology: pathophysiology, tumor biology and implications for treatment. Q J Nucl Med Mol Imag 57:219–234 Busk M, Horsman MR (2013) Relevance of hypoxia in radiation oncology: pathophysiology, tumor biology and implications for treatment. Q J Nucl Med Mol Imag 57:219–234
83.
go back to reference Cosse J-P, Michiels C (2008) Tumour hypoxia affects the responsiveness of cancer cells to chemotherapy and promotes cancer progression. Anticancer Agents Med Chem 8:790–797PubMedCrossRef Cosse J-P, Michiels C (2008) Tumour hypoxia affects the responsiveness of cancer cells to chemotherapy and promotes cancer progression. Anticancer Agents Med Chem 8:790–797PubMedCrossRef
84.
go back to reference Luk CK, Veinot-Drebot L, Tjan E, Tannock IF (1990) Effect of transient hypoxia on sensitivity to doxorubicin in human and murine cell lines. J Natl Cancer Inst 82:684–692PubMedCrossRef Luk CK, Veinot-Drebot L, Tjan E, Tannock IF (1990) Effect of transient hypoxia on sensitivity to doxorubicin in human and murine cell lines. J Natl Cancer Inst 82:684–692PubMedCrossRef
85.
go back to reference Young SD, Hill RP (1990) Effects of reoxygenation on cells from hypoxic regions of solid tumors: anticancer drug sensitivity and metastatic potential. J Natl Cancer Inst 82:371–380PubMedCrossRef Young SD, Hill RP (1990) Effects of reoxygenation on cells from hypoxic regions of solid tumors: anticancer drug sensitivity and metastatic potential. J Natl Cancer Inst 82:371–380PubMedCrossRef
86.
go back to reference Sanna K, Rofstad EK (1994) Hypoxia-induced resistance to doxorubicin and methotrexate in human melanoma cell lines in vitro. Int J Cancer 58:258–262PubMedCrossRef Sanna K, Rofstad EK (1994) Hypoxia-induced resistance to doxorubicin and methotrexate in human melanoma cell lines in vitro. Int J Cancer 58:258–262PubMedCrossRef
90.
go back to reference Curiel TJ, Coukos G, Zou L et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949. doi:10.1038/nm1093 PubMedCrossRef Curiel TJ, Coukos G, Zou L et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949. doi:10.​1038/​nm1093 PubMedCrossRef
93.
go back to reference Leung DW, Cachianes G, Kuang WJ et al (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309PubMedCrossRef Leung DW, Cachianes G, Kuang WJ et al (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309PubMedCrossRef
94.
go back to reference Senger DR, Galli SJ, Dvorak AM et al (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219:983–985PubMedCrossRef Senger DR, Galli SJ, Dvorak AM et al (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219:983–985PubMedCrossRef
96.
go back to reference Ohtsu A, Shah MA, Van Cutsem E et al (2011) Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 29:3968–3976. doi:10.1200/JCO.2011.36.2236 PubMedCrossRef Ohtsu A, Shah MA, Van Cutsem E et al (2011) Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 29:3968–3976. doi:10.​1200/​JCO.​2011.​36.​2236 PubMedCrossRef
97.
go back to reference Reck M, von Pawel J, Zatloukal P et al (2009) Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 27:1227–1234. doi:10.1200/JCO.2007.14.5466 PubMedCrossRef Reck M, von Pawel J, Zatloukal P et al (2009) Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 27:1227–1234. doi:10.​1200/​JCO.​2007.​14.​5466 PubMedCrossRef
104.
go back to reference 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 6:553–563. doi:10.1016/j.ccr.2004.10.011 PubMed 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 6:553–563. doi:10.​1016/​j.​ccr.​2004.​10.​011 PubMed
106.
109.
go back to reference Martin JD, Fukumura D, Duda DG et al (2016) Reengineering the tumor microenvironment to alleviate hypoxia and overcome cancer heterogeneity. Cold Spring Harb Perspect Med. doi:10.1101/cshperspect.a027094 Martin JD, Fukumura D, Duda DG et al (2016) Reengineering the tumor microenvironment to alleviate hypoxia and overcome cancer heterogeneity. Cold Spring Harb Perspect Med. doi:10.​1101/​cshperspect.​a027094
119.
go back to reference Witzenbichler B, Maisonpierre PC, Jones P et al (1998) Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial-specific receptor tyrosine kinase Tie2. J Biol Chem 273:18514–18521PubMedCrossRef Witzenbichler B, Maisonpierre PC, Jones P et al (1998) Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial-specific receptor tyrosine kinase Tie2. J Biol Chem 273:18514–18521PubMedCrossRef
120.
go back to reference Jones N, Master Z, Jones J et al (1999) Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration. J Biol Chem 274:30896–30905PubMedCrossRef Jones N, Master Z, Jones J et al (1999) Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration. J Biol Chem 274:30896–30905PubMedCrossRef
121.
go back to reference Hayes AJ, Huang WQ, Mallah J et al (1999) Angiopoietin-1 and its receptor Tie-2 participate in the regulation of capillary-like tubule formation and survival of endothelial cells. Microvasc Res 58:224–237. doi:10.1006/mvre.1999.2179 PubMedCrossRef Hayes AJ, Huang WQ, Mallah J et al (1999) Angiopoietin-1 and its receptor Tie-2 participate in the regulation of capillary-like tubule formation and survival of endothelial cells. Microvasc Res 58:224–237. doi:10.​1006/​mvre.​1999.​2179 PubMedCrossRef
122.
go back to reference Teichert-Kuliszewska K, Maisonpierre PC, Jones N et al (2001) Biological action of angiopoietin-2 in a fibrin matrix model of angiogenesis is associated with activation of Tie2. Cardiovasc Res 49:659–670PubMedCrossRef Teichert-Kuliszewska K, Maisonpierre PC, Jones N et al (2001) Biological action of angiopoietin-2 in a fibrin matrix model of angiogenesis is associated with activation of Tie2. Cardiovasc Res 49:659–670PubMedCrossRef
123.
go back to reference Kwak HJ, So JN, Lee SJ et al (1999) Angiopoietin-1 is an apoptosis survival factor for endothelial cells. FEBS Lett 448:249–253PubMedCrossRef Kwak HJ, So JN, Lee SJ et al (1999) Angiopoietin-1 is an apoptosis survival factor for endothelial cells. FEBS Lett 448:249–253PubMedCrossRef
124.
go back to reference Kim I, Kim JH, Moon SO et al (2000) Angiopoietin-2 at high concentration can enhance endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Oncogene 19:4549–4552. doi:10.1038/sj.onc.1203800 PubMedCrossRef Kim I, Kim JH, Moon SO et al (2000) Angiopoietin-2 at high concentration can enhance endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Oncogene 19:4549–4552. doi:10.​1038/​sj.​onc.​1203800 PubMedCrossRef
125.
127.
go back to reference Leow CC, Coffman K, Inigo I et al (2012) MEDI3617, a human anti-angiopoietin 2 monoclonal antibody, inhibits angiogenesis and tumor growth in human tumor xenograft models. Int J Oncol 40:1321–1330. doi:10.3892/ijo.2012.1366 PubMed Leow CC, Coffman K, Inigo I et al (2012) MEDI3617, a human anti-angiopoietin 2 monoclonal antibody, inhibits angiogenesis and tumor growth in human tumor xenograft models. Int J Oncol 40:1321–1330. doi:10.​3892/​ijo.​2012.​1366 PubMed
132.
133.
go back to reference Monk BJ, Poveda A, Vergote I et al (2016) Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): long-term survival, impact of ascites, and progression-free survival-2. Gynecol Oncol 143:27–34. doi:10.1016/j.ygyno.2016.07.112 PubMedCrossRef Monk BJ, Poveda A, Vergote I et al (2016) Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): long-term survival, impact of ascites, and progression-free survival-2. Gynecol Oncol 143:27–34. doi:10.​1016/​j.​ygyno.​2016.​07.​112 PubMedCrossRef
136.
139.
go back to reference Huang J, Soffer SZ, Kim ES et al (2004) Vascular remodeling marks tumors that recur during chronic suppression of angiogenesis. Mol Cancer Res MCR 2:36–42PubMed Huang J, Soffer SZ, Kim ES et al (2004) Vascular remodeling marks tumors that recur during chronic suppression of angiogenesis. Mol Cancer Res MCR 2:36–42PubMed
141.
go back to reference Erber R, Thurnher A, Katsen AD et al (2004) Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J 18:338–340. doi:10.1096/fj.03-0271fje PubMed Erber R, Thurnher A, Katsen AD et al (2004) Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J 18:338–340. doi:10.​1096/​fj.​03-0271fje PubMed
142.
143.
go back to reference Hawthorne T, Giot L, Blake L et al (2008) A phase I study of CR002, a fully-human monoclonal antibody against platelet-derived growth factor-D. Int J Clin Pharmacol Ther 46:236–244PubMedCrossRef Hawthorne T, Giot L, Blake L et al (2008) A phase I study of CR002, a fully-human monoclonal antibody against platelet-derived growth factor-D. Int J Clin Pharmacol Ther 46:236–244PubMedCrossRef
144.
go back to reference Jayson GC, Parker GJM, Mullamitha S et al (2005) Blockade of platelet-derived growth factor receptor-beta by CDP860, a humanized, PEGylated di-Fab’, leads to fluid accumulation and is associated with increased tumor vascularized volume. J Clin Oncol 23:973–981. doi:10.1200/JCO.2005.01.032 PubMedCrossRef Jayson GC, Parker GJM, Mullamitha S et al (2005) Blockade of platelet-derived growth factor receptor-beta by CDP860, a humanized, PEGylated di-Fab’, leads to fluid accumulation and is associated with increased tumor vascularized volume. J Clin Oncol 23:973–981. doi:10.​1200/​JCO.​2005.​01.​032 PubMedCrossRef
145.
go back to reference Shen J, Vil MD, Prewett M et al (2009) Development of a fully human anti-PDGFRbeta antibody that suppresses growth of human tumor xenografts and enhances antitumor activity of an anti-VEGFR2 antibody. Neoplasia NY N 11:594–604CrossRef Shen J, Vil MD, Prewett M et al (2009) Development of a fully human anti-PDGFRbeta antibody that suppresses growth of human tumor xenografts and enhances antitumor activity of an anti-VEGFR2 antibody. Neoplasia NY N 11:594–604CrossRef
147.
148.
go back to reference Davis DW, Takamori R, Raut CP et al (2005) Pharmacodynamic analysis of target inhibition and endothelial cell death in tumors treated with the vascular endothelial growth factor receptor antagonists SU5416 or SU6668. Clin Cancer Res 11:678–689PubMedCrossRef Davis DW, Takamori R, Raut CP et al (2005) Pharmacodynamic analysis of target inhibition and endothelial cell death in tumors treated with the vascular endothelial growth factor receptor antagonists SU5416 or SU6668. Clin Cancer Res 11:678–689PubMedCrossRef
156.
go back to reference Valdimarsdottir G, Goumans M-J, Rosendahl A et al (2002) Stimulation of Id1 expression by bone morphogenetic protein is sufficient and necessary for bone morphogenetic protein-induced activation of endothelial cells. Circulation 106:2263–2270PubMedCrossRef Valdimarsdottir G, Goumans M-J, Rosendahl A et al (2002) Stimulation of Id1 expression by bone morphogenetic protein is sufficient and necessary for bone morphogenetic protein-induced activation of endothelial cells. Circulation 106:2263–2270PubMedCrossRef
160.
go back to reference Scharpfenecker M, van Dinther M, Liu Z et al (2007) BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis. J Cell Sci 120:964–972. doi:10.1242/jcs.002949 PubMedCrossRef Scharpfenecker M, van Dinther M, Liu Z et al (2007) BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis. J Cell Sci 120:964–972. doi:10.​1242/​jcs.​002949 PubMedCrossRef
164.
go back to reference Makker V, Filiaci VL, Chen L-M et al (2015) Phase II evaluation of dalantercept, a soluble recombinant activin receptor-like kinase 1 (ALK1) receptor fusion protein, for the treatment of recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study 0229N. Gynecol Oncol 138:24–29. doi:10.1016/j.ygyno.2015.04.006 PubMedPubMedCentralCrossRef Makker V, Filiaci VL, Chen L-M et al (2015) Phase II evaluation of dalantercept, a soluble recombinant activin receptor-like kinase 1 (ALK1) receptor fusion protein, for the treatment of recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study 0229N. Gynecol Oncol 138:24–29. doi:10.​1016/​j.​ygyno.​2015.​04.​006 PubMedPubMedCentralCrossRef
165.
go back to reference Wang X, Solban N, Khanna P et al (2016) Inhibition of ALK1 signaling with dalantercept combined with VEGFR TKI leads to tumor stasis in renal cell carcinoma. Oncotarget. doi:10.18632/oncotarget.9621 Wang X, Solban N, Khanna P et al (2016) Inhibition of ALK1 signaling with dalantercept combined with VEGFR TKI leads to tumor stasis in renal cell carcinoma. Oncotarget. doi:10.​18632/​oncotarget.​9621
166.
167.
go back to reference Necchi A, Giannatempo P, Mariani L et al (2014) PF-03446962, a fully-human monoclonal antibody against transforming growth-factor β (TGFβ) receptor ALK1, in pre-treated patients with urothelial cancer: an open label, single-group, phase 2 trial. Invest New Drugs 32:555–560. doi:10.1007/s10637-014-0074-9 PubMedCrossRef Necchi A, Giannatempo P, Mariani L et al (2014) PF-03446962, a fully-human monoclonal antibody against transforming growth-factor β (TGFβ) receptor ALK1, in pre-treated patients with urothelial cancer: an open label, single-group, phase 2 trial. Invest New Drugs 32:555–560. doi:10.​1007/​s10637-014-0074-9 PubMedCrossRef
168.
go back to reference Wilson CW, Ye W (2014) Regulation of vascular endothelial junction stability and remodeling through Rap1-Rasip1 signaling. Cell Adhes Migr 8:76–83CrossRef Wilson CW, Ye W (2014) Regulation of vascular endothelial junction stability and remodeling through Rap1-Rasip1 signaling. Cell Adhes Migr 8:76–83CrossRef
170.
go back to reference Agrawal V, Maharjan S, Kim K et al (2014) Direct endothelial junction restoration results in significant tumor vascular normalization and metastasis inhibition in mice. Oncotarget 5:2761–2777PubMedPubMedCentralCrossRef Agrawal V, Maharjan S, Kim K et al (2014) Direct endothelial junction restoration results in significant tumor vascular normalization and metastasis inhibition in mice. Oncotarget 5:2761–2777PubMedPubMedCentralCrossRef
174.
go back to reference Le Bras A, Lionneton F, Mattot V et al (2007) HIF-2alpha specifically activates the VE-cadherin promoter independently of hypoxia and in synergy with Ets-1 through two essential ETS-binding sites. Oncogene 26:7480–7489. doi:10.1038/sj.onc.1210566 PubMedCrossRef Le Bras A, Lionneton F, Mattot V et al (2007) HIF-2alpha specifically activates the VE-cadherin promoter independently of hypoxia and in synergy with Ets-1 through two essential ETS-binding sites. Oncogene 26:7480–7489. doi:10.​1038/​sj.​onc.​1210566 PubMedCrossRef
175.
go back to reference Kleibeuker EA, Fokas E, Allen PD et al (2016) Low dose angiostatic treatment counteracts radiotherapy-induced tumor perfusion and enhances the anti-tumor effect. Oncotarget. doi:10.18632/oncotarget.12814 Kleibeuker EA, Fokas E, Allen PD et al (2016) Low dose angiostatic treatment counteracts radiotherapy-induced tumor perfusion and enhances the anti-tumor effect. Oncotarget. doi:10.​18632/​oncotarget.​12814
179.
go back to reference Daskalow K, Rohwer N, Raskopf E et al (2010) Role of hypoxia-inducible transcription factor 1alpha for progression and chemosensitivity of murine hepatocellular carcinoma. J Mol Med Berl Ger 88:817–827. doi:10.1007/s00109-010-0623-4 CrossRef Daskalow K, Rohwer N, Raskopf E et al (2010) Role of hypoxia-inducible transcription factor 1alpha for progression and chemosensitivity of murine hepatocellular carcinoma. J Mol Med Berl Ger 88:817–827. doi:10.​1007/​s00109-010-0623-4 CrossRef
181.
Metadata
Title
Tumor angiogenesis and vascular normalization: alternative therapeutic targets
Authors
Claire Viallard
Bruno Larrivée
Publication date
01-11-2017
Publisher
Springer Netherlands
Published in
Angiogenesis / Issue 4/2017
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-017-9562-9

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