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110. Dougher-Vermazen M, Hulmes JD, Böhlen P, Terman BI (1994) Biological activity and
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111. Fuh G, Li B, Crowley C et al (1998) Requirements for binding and signaling of the kinase
domain receptor for vascular endothelial growth factor. J Biol Chem 273:11197–11204.
https://doi.org/10.1074/jbc.273.18.11197
112. Roskoski R (2008) VEGF receptor protein-tyrosine kinases: structure and regulation. Biochem
Biophys Res Commun 375:287–291
113. Simons M, Gordon E, Claesson-Welsh L (2016) Mechanisms and regulation of endothelial
VEGF receptor signalling. Nat Rev Mol Cell Biol 17:611–625. https://doi.org/10.1038/nrm.
2016.87
114. Youssoufian H, Hicklin DJ, Rowinsky EK (2007) Review: monoclonal antibodies to the
vascular endothelial growth factor receptor-2 in cancer therapy. Clin Cancer Res 13:5544s–
5548s. https://doi.org/10.1158/1078-0432.CCR-07-1107
115. Sitohy B, Nagy JA, Dvorak HF (2012) Anti-VEGF/VEGFR therapy for cancer: reassessing
the target. Cancer Res 72:1909–1914. https://doi.org/10.1158/0008-5472.CAN-11-3406
116. Xu D, Wang T-L, Sun L-P, You Q-D (2011) Recent progress of small molecular VEGFR
inhibitors as anticancer agents. Mini Rev Med Chem 11:18–31. https://doi.org/10.2174/
138955711793564015
117. Zhang J, Shan Y, Pan X, He L (2011) Recent advances in antiangiogenic agents with VEGFR
as target. Mini Rev Med Chem 11:920–946. https://doi.org/10.2174/138955711797068355
118. Sharma PS, Sharma R, Tyagi T (2011) VEGF/VEGFR pathway inhibitors as anti-angiogenic
agents: present and future. Curr Cancer Drug Targets 11:624–653
198
L. M. Lima et al.
signaling in angiogenesis: a crucial target for anti- and pro-Angiogenic therapies. Genes
Cancer 2:1097–1105. https://doi.org/10.1177/1947601911423031
100. Takahashi S (2011) Vascular endothelial growth factor (VEGF), VEGF receptors and their
inhibitors for antiangiogenic tumour therapy. Biol Pharm Bull 34:1785–1788. https://doi.org/
10.1248/bpb.34.1785
101. Adams RH, Alitalo K (2007) Molecular regulation of angiogenesis and lymphangiogenesis.
Nat Rev Mol Cell Biol 8:464–478. https://doi.org/10.1038/nrm2183
102. Bergers G, Benjamin LE (2003) Tumourigenesis and the angiogenic switch. Nat Rev Cancer
3:401–410. https://doi.org/10.1038/nrc1093
103. Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438:932–936. https://
doi.org/10.1038/nature04478
104. Hoeben A, Landuyt B, Highley MS et al (2004) Vascular endothelial growth factor and
angiogenesis. Pharmacol Rev 56:549–580. https://doi.org/10.1124/pr.56.4.3.549
105. Schenone S, Bondavalli F, Botta M (2007) Antiangiogenic agents: an update on small
molecule VEGFR inhibitors. Curr Med Chem 14:2495–2516. https://doi.org/10.2174/
092986707782023622
106. Moreira IS, Fernandes PA, Ramos MJ (2007) Vascular endothelial growth factor (VEGF)
inhibition – a critical review. Anti Cancer Agents Med Chem 7:223–245
107. Lee SH, Jeong D, Han Y-S, Baek MJ (2015) Pivotal role of vascular endothelial growth factor
pathway in tumour angiogenesis. Ann Surg Treat Res 89:1–8. https://doi.org/10.4174/astr.
2015.89.1.1
108. Holmes DIR, Zachary I (2005) The vascular endothelial growth factor (VEGF) family:
angiogenic factors in health and disease. Genome Biol 6:209. https://doi.org/10.1186/gb2005-6-2-209
109. Terman BI, Carrion ME, Kovacs E et al (1991) Identification of a new endothelial cell growth
factor receptor tyrosine kinase. Oncogene 6:1677–1683. https://doi.org/10.1383/surg.23.2.37.
60352
110. Dougher-Vermazen M, Hulmes JD, Böhlen P, Terman BI (1994) Biological activity and
phosphorylation sites of the bacterially expressed cytosolic domain of the KDR VEGFreceptor. Biochem Biophys Res Commun 205:728–738
111. Fuh G, Li B, Crowley C et al (1998) Requirements for binding and signaling of the kinase
domain receptor for vascular endothelial growth factor. J Biol Chem 273:11197–11204.
https://doi.org/10.1074/jbc.273.18.11197
112. Roskoski R (2008) VEGF receptor protein-tyrosine kinases: structure and regulation. Biochem
Biophys Res Commun 375:287–291
113. Simons M, Gordon E, Claesson-Welsh L (2016) Mechanisms and regulation of endothelial
VEGF receptor signalling. Nat Rev Mol Cell Biol 17:611–625. https://doi.org/10.1038/nrm.
2016.87
114. Youssoufian H, Hicklin DJ, Rowinsky EK (2007) Review: monoclonal antibodies to the
vascular endothelial growth factor receptor-2 in cancer therapy. Clin Cancer Res 13:5544s–
5548s. https://doi.org/10.1158/1078-0432.CCR-07-1107
115. Sitohy B, Nagy JA, Dvorak HF (2012) Anti-VEGF/VEGFR therapy for cancer: reassessing
the target. Cancer Res 72:1909–1914. https://doi.org/10.1158/0008-5472.CAN-11-3406
116. Xu D, Wang T-L, Sun L-P, You Q-D (2011) Recent progress of small molecular VEGFR
inhibitors as anticancer agents. Mini Rev Med Chem 11:18–31. https://doi.org/10.2174/
138955711793564015
117. Zhang J, Shan Y, Pan X, He L (2011) Recent advances in antiangiogenic agents with VEGFR
as target. Mini Rev Med Chem 11:920–946. https://doi.org/10.2174/138955711797068355
118. Sharma PS, Sharma R, Tyagi T (2011) VEGF/VEGFR pathway inhibitors as anti-angiogenic
agents: present and future. Curr Cancer Drug Targets 11:624–653
198
L. M. Lima et al.