Advanced search
Publication Cover
Expert Opinion on Drug Discovery Volume 4, 2009 - Issue 9
Submit an article Journal homepage
177
Views
19
CrossRef citations to date
0
Altmetric
Reviews

Current status and future prospects for anti-angiogenic therapies in cancer

Carolyn A Staton University of Sheffield, School of Medicine and Biomedical Sciences, Microcirculation Research Group, Academic Unit of Surgical Oncology, Beech Hill Road, Sheffield, South Yorkshire, S10 2RX, UK +44 (0)114 226 5852; +44 (0)114 271 3314; [email protected]
,
Nicola J Brown University of Sheffield, School of Medicine and Biomedical Sciences, Microcirculation Research Group, Academic Unit of Surgical Oncology, Beech Hill Road, Sheffield, South Yorkshire, S10 2RX, UK +44 (0)114 226 5852; +44 (0)114 271 3314; [email protected]
&
Malcolm WR Reed University of Sheffield, School of Medicine and Biomedical Sciences, Microcirculation Research Group, Academic Unit of Surgical Oncology, Beech Hill Road, Sheffield, South Yorkshire, S10 2RX, UK +44 (0)114 226 5852; +44 (0)114 271 3314; [email protected]
Pages 961-979 | Published online: 20 Aug 2009

Bibliography

  • Algire GH, Chalkley HW, Legallais FY, Park HD. Vascular reactions of normal and malignant tissues in vivo. I. Vascular reactions of mice to wounds and to normal neoplastic transformations. J Natl Cancer Inst 1945;6:73-85
  • Gimbrone MA Jr, Leapman SB, Cotran RS, Folkman J. Tumor dormancy in vivo by prevention of neovascularisation. J Exp Med 1972;136:261-76
  • Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182-6
  • Folkman J, Watson K, Ingber D, Hanahan D. Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 1989;339:58-61
  • Peckham M, Pinedo HM, Verosnesi U, editors, Oxford Textbook of Oncology. Oxford University Press Oxford: UK; 1995
  • Staton CA, Chetwood AS, Cameron IC, et al. The angiogenic switch occurs at the adenoma stage of the adenoma carcinoma sequence in colorectal cancer. Gut 2007;56:1426-32
  • Bluff JE, Brown NJ, Reed MWR, Staton CA. Assessment of angiogenesis, vascular endothelial growth factor and tissue factor in human breast cancer. Microcirculation 2007;14:638 (OC3)
  • Menakuru SR, Brown NJ, Staton CA, Reed MW. Angiogenesis in pre-malignant conditions. Br J Cancer 2008;99:1961-6
  • Ferrara N. Role of vascular endothelial growth factor in physiologic and pathologic angiogenesis: therapeutic implications. Semin Oncol 2002;29:10-4
  • Coffelt SB, Hughes R, Lewis CE. Tumor-associated macrophages: effectors of angiogenesis and tumor progression. Biochim Biophys Acta 2009. [Epub ahead of print]
  • De Palma M, Venneri MA, Galli R, 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;8:211-26
  • Shojaei F, Wu X, Malik AK, et al. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol 2007;25:911-20
  • Parr C, Watkins G, Boulton M, et al. Placenta growth factor is over-expressed and has prognostic value in human breast cancer Eur J Cancer 2005;41:2819-27
  • Kowanetz M, Ferrara N. Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res 2006;12:5018-22
  • Harper SJ, Bates DO. VEGF-A splicing: the key to anti-angiogenic therapeutics? Nat Rev Cancer 2008;8:880-7
  • Ellis LM, Hicklin DJ. VEGF targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 2008;8:579-91
  • Witmer AN, van Blijswijk BC, Dai J, et al. VEGFR-3 in adult angiogenesis. J Pathol 2001;195:490-7
  • Joukov V, Pajusola K, Kaipainen A, et al. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J 1996;15:290-8
  • Jakeman LB, Winer J, Bennett GL, et al. Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues. J Clin Invest 1992;89:244-53
  • Jakeman LB, Armanini M, Phillips HS, Ferrara N. Developmental expression of binding sites and messenger ribonucleic acid for vascular endothelial growth factor suggests a role for this protein in vasculogenesis and angiogenesis. Endocrinology 1993;133:848-59
  • Staton CA, Kumar I, Reed MW, Brown NJ. Neuropilins in physiological and pathological angiogenesis. J Pathol 2007;212:237-48
  • Kolodkin AL, Levengood DV, Rowe EG, et al. Neuropilin is a semaphorin III receptor. Cell 1997;90:753-62
  • Cai H, Reed RR. Cloning and characterization of neuropilin-1-interacting protein: a PSD-95/Dlg/ZO-1 domain-containing protein that interacts with the cytoplasmic domain of neuropilin-1. J Neurosci 1999;19:6519-27
  • Bachelder RE, Crago A, Chung J, et al. Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells. Cancer Res 2001;61:5736-40
  • 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;85:357-68
  • Barr MP, Byrne AM, Duffy AM, et al. A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells. Br J Cancer 2005;92:328-33
  • Stephenson JM, Banerjee S, Saxena NK, et al. Neuropilin-1 is differentially expressed in myoepithelial cells and vascular smooth muscle cells in preneoplastic and neoplastic human breast: a possible marker for the progression of breast cancer. Int J Cancer 2002;101:409-14
  • Stouffer RL, Xu F, Duffy DM. Molecular control of ovulation and luteinization in the primate follicle. Front Biosci 2007;12:297-307
  • Poon RT, Fan ST, Wong J. Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol 2001;19:1207-25
  • Zhang J, Jia Z, Li Q, et al. Elevated expression of vascular endothelial growth factor correlates with increased angiogenesis and decreased progression-free survival among patients with low-grade neuroendocrine tumors. Cancer 2007;109:1478-86
  • Soker S, Kaefer M, Johnson M, et al. Vascular endothelial growth factor-mediated autocrine stimulation of prostate tumor cells coincides with progression to a malignant phenotype. Am J Pathol 2001;159:651-9
  • Kumar ID, Cross SS, Claydon P, et al. Vascular endothelial growth factor and its receptor pattern in invasive human breast cancer. Microcirculation 2005;12:663 P7
  • Thurston G, Kitajewski J. VEGF and Delta-Notch: interacting signalling pathways in tumour angiogenesis. Br J Cancer 2008;99:1204-9
  • Shawber CJ, Das I, Francisco E, et al. Notch signaling in primary endothelial cells. Ann NY Acad Sci 2003;995:162-70
  • Yan M, Plowman GD. Delta-like 4/Notch signaling and its therapeutic implications. Clin Cancer Res 2007;13:7243-6
  • Krebs LT, Xue Y, Norton CR, et al. Notch signalling is essential for vascular morphogenesis in mice. Genes Dev 2000;14:1343-52
  • Xue Y, Gao X, Lindsell CE, et al. Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged 1. Hum Mol Genet 1999;8:723-30
  • Krebs LT, Shutter JR, Tanigaki K, et al. Haploinsufficienct lethality and formation of arteriovenous malformations in Notch pathway mutants. Genes Dev 2004;18:2469-73
  • Noguera-Troise I, Daly C, Papadopoulos NJ, et al. Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature 2006;444:1032-7
  • Mailhos C, Modlich U, Lewis J, et al. Delta4, an endothelial specific notch ligand expressed at sites of physiological and tumour angiogenesis. Differentiation 2001;69:135-44
  • Patel NS, Li JL, Generali D, et al. Up-regulation of delta-like 4 ligand in human tumour vasculature and the role of basal expression in endothelial cell function. Cancer Res 2005;65:8690-7
  • Patel NS, Dobbie MS, Rochester M, et al. Up-regulation of endothelial delta-like 4 expression correlates with vessel maturation in bladder cancer. Clin Cancer Res 2006;12:4836-44
  • Williams CK, Li JL, Murga M, et al. Up-regulation of the Notch ligand Delta-like 4 inhibits VEGF-induced endothelial cell function. Blood 2006;107:931-9
  • Harrington LS, Sainson RC, Williams CK, et al. Regulation of multiple angiogenic pathways by Dll4 and Notch in human umbilical vein endothelial cells. Microvasc Res 2008;75:144-54
  • Gerhardt H. VEGF and endothelial guidance in angiogenic sprouting. Organogenesis 2008;4:241-6
  • Betsholtz C. Insight into the physiological functions of PDGF through genetic studies in mice. Cytokine Growth Factor Rev 2004;15:215-28
  • Gerhardt H, Golding M, Fruttiger M, et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 2003;16:1163-77
  • Bergers G, Song S. The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol 2005;7:452-64
  • Lindahl P, Johansson BR, Levéen P, Betsholtz C. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 1997;277:242-5
  • Hellström M, Kalén M, Lindahl P, et al. Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development 1999;126:3047-55
  • Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res 2005;97:512-23
  • Mandriota SJ, Menoud PA, Pepper MS. Transforming growth factor beta 1 down-regulates vascular endothelial growth factor receptor 2/flk-1 expression in vascular endothelial cells. J Biol Chem 1996;271:11500-5
  • Hirschi KK, Rohovsky SA, D'Amore PA. PDGF, TGF-beta, and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate. J Cell Biol 1998;141:805-14
  • Hirschi KK, D'Amore PA. Control of angiogenesis by the pericyte: molecular mechanisms and significance. EXS 1997;79:419-28
  • Dabrow MB, Francesco MR, McBrearty FX, Caradonna S. The effects of platelet derived growth factor and receptor on normal and neoplastic human ovarian surface epithelium. Gynecol Oncol 1998;71:29-37
  • Arteaga CL. The epidermal growth factor receptor: from mutant oncogene in non-human cancers to therapeutic target in human neoplasia. J Clin Oncol 2001;19:32-40S
  • Ellis LM. Epidermal growth factor receptor in tumor angiogenesis. Hematol Oncol Clin North Am 2004;18:1007-21
  • Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001;2:127-37
  • Perrotte P, Matsumoto T, Inoue K, et al. Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. Clin Cancer Res 1999;5:257-65
  • Kim SJ, Uehara H, Karashima T, et al. Blockade of epidermal growth factor receptor signaling in tumor cells and tumor-associated endothelial cells for therapy of androgen-independent human prostate cancer growing in the bone of nude mice. Clin Cancer Res 2003;9:1200-10
  • Bach F, Uddin FJ, Burke D. Angiopoietins in malignancy. Eur J Surg Oncol 2007;33:7-15
  • Xu Y, Yu Q. Angiopoietin-1, unlike angiopoietin-2, is incorporated into the extracellular matrix via its linker peptide region. J Biol Chem 2001;276:34990-8
  • Fiedler U, Scharpfenecker M, Koidl S, et al. The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. Blood 2004;103:4150-6
  • Suri C, Jones PF, Patan S, et al. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 1996;87:1171-80
  • Gale NW, Thurston G, Hackett SF, et al. Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1. Dev Cell 2002;3:411-23
  • Jones N, Iljin K, Dumont DJ, Alitalo K. Tie receptors: new modulators of angiogenic and lymphangiogenic responses. Nat Rev Mol Cell Biol 2001;2:257-67
  • Wilkinson DG. Multiple roles of EPH receptors and ephrins in neural development. Nat Rev Neurosci 2001;2:155-64
  • Gale NW, Holland SJ, Valenzuela DM, et al. Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis. Neuron 1996;17:9-19
  • Wang HU, Chen ZF, Anderson DJ. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 1998;93:741-53
  • Ogawa K, Pasqualini R, Lindberg RA, et al. The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularisation. Oncogene 2000;19:6043-52
  • Cheng N, Brantley DM, Chen J. The ephrins and Eph receptors in angiogenesis. Cytokine Growth Factor Rev 2002;13:75-85
  • Cheng N, Brantley DM, Liu H, et al. Blockade of EphA receptor tyrosine kinase activation inhibits vascular endothelial cell growth factor-induced angiogenesis. Mol Cancer Res 2002;1:2-11
  • Legg JA, Herbert JM, Clissold P, Bicknell R. Slits and Roundabouts in cancer, tumour angiogenesis and endothelial cell migration. Angiogenesis 2008;11:13-21
  • Huminiecki L, Bicknell R. In silico cloning of novel endothelial-specific genes. Genome Res 2000;10:1796-806
  • Bedell VM, Yeo SY, Park KW, et al. Roundabout4 is essential for angiogenesis in vivo. Proc Natl Acad Sci USA 2005;102:6373-8
  • Wang B, Xiao Y, Ding BB, et al. Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity. Cancer Cell 2003;4:19-29
  • Suchting S, Heal P, Tahtis K, et al. Soluble Robo4 receptor inhibits in vivo angiogenesis and endothelial cell migration. FASEB J 2005;19:121-3
  • Mollay C, Wechselberger C, Mignogna G, et al. Bv8, a small protein from frog skin and its homologue from snake venom induce hyperalgesia in rats. Eur J Pharmacol 1999;374:189-96
  • Negri L, Lattanzi R, Giannini E, Melchiorri P. Bv8/Prokineticin proteins and their receptors. Life Sci 2007;81:1103-16
  • LeCouter J, Kowalski J, Foster J, et al. Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature 2001;412:877-84
  • LeCouter J, Lin R, Tejada M, et al. The endocrine-gland-derived VEGF homologue Bv8 promotes angiogenesis in the testis: localization of Bv8 receptors to endothelial cells. Proc Natl Acad Sci USA 2003;100:2685-90
  • Shojaei F, Wu X, Zhong C, et al. Bv8 regulates myeloid-cell-dependent tumour angiogenesis. Nature 2007;450:825-31
  • Taylor S, Folkman J. Protamine is an inhibitor of angiogenesis. Nature 1982;297:307-12
  • Crum R, Szabo S, Folkman J. A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. Science 1985;230:1375-8
  • O'Reilly MS, Holmgren L, Shing Y, et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994;79:315-28
  • O'Reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997;88:277-85
  • Herbst RS, Hess KR, Tran HT, et al. Phase I study of recombinant human endostatin in patients with advanced solid tumors. J Clin Oncol 2002;20:3792-803
  • Eder JP Jr, Supko JG, Clark JW, et al. Phase I clinical trial of recombinant human endostatin administered as a short intravenous infusion repeated daily. J Clin Oncol 2002;20:3772-84
  • Kulke MH, Bergsland EK, Ryan DP, et al. Phase II study of recombinant human endostatin in patients with advanced neuroendocrine tumors. J Clin Oncol 2006;24:3555-61
  • Antoine N, Greimers R, De Roanne C, et al. AGM-1470, a potent angiogenesis inhibitor, prevents the entry of normal but not transformed endothelial cells into the G1 phase of the cell cycle. Cancer Res 1994;54:2073-6
  • Folkman J, Kalluri R. Cancer without disease. Nature 2004;427:787
  • Kudelka AP, Levy T, Verschraegen CF, et al. A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix. Clin Cancer Res 1997;3:1501-5
  • Kudelka AP, Verschraegen CF, Loyer E. Complete remission of metastatic cervical cancer with the angiogenesis inhibitor TNP-470. N Engl J Med 1998;338:991-2
  • Herbst RS, Madden TL, Tran HT, et al. Safety and pharmacokinetic effects of TNP-470, an angiogenesis inhibitor, combined with paclitaxel in patients with solid tumors: evidence for activity in non-small-cell lung cancer. J Clin Oncol 2002;20:4440-7
  • Drevs J, Laus C, Medinger M, et al. Antiangiogenesis: current clinical data and future perspectives. Onkologie 2002;25:520-7
  • Rundhaug JE. Matrix metalloproteinases and angiogenesis. J Cell Mol Med 2005;9:267-85
  • Matsuyama Y, Takao S, Aikou T. Comparison of matrix metalloproteinase expression between primary tumors with or without liver metastasis in pancreatic and colorectal carcinomas. J Surg Oncol 2002;80:105-10
  • Rothenberg ML, Nelson AR, Hande KR. New drugs on the horizon: matrix metalloproteinase inhibitors. Oncologist 1998;3:271-4
  • Brown PD, Giavazzi R. Matrix metalloproteinase inhibition: a review of anti-tumour activity. Ann Oncol 1995;6:967-74
  • Groves MD, Puduvalli VK, Hess KR, et al. Phase II trial of temozolomide plus the matrix metalloproteinase inhibitor, marimastat, in recurrent and progressive glioblastoma multiforme. J Clin Oncol 2002;20:1383-8
  • Sparano JA, Bernardo P, Stephenson P, et al. Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196. J Clin Oncol 2004;22:4683-90
  • Rosenbaum E, Zahurak M, Sinibaldi V, et al. Marimastat in the treatment of patients with biochemically relapsed prostate cancer: a prospective randomized, double-blind, phase I/II trial. Clin Cancer Res 2005;11:4437-43
  • Borges E, Jan Y, Ruoslahti E. Platelet-derived growth factor receptor beta and vascular endothelial growth factor receptor 2 bind to the beta 3 integrin through its extracellular domain. J Biol Chem 2000;275:39867-73
  • Soldi R, Mitola S, Strasly M, et al. Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. EMBO J 1999;18:882-92
  • Ellis IR, Schor AM, Schor SL. EGF AND TGF-alpha motogenic activities are mediated by the EGF receptor via distinct matrix-dependent mechanisms. Exp Cell Res 2007;313:732-41
  • Sahni A, Francis CW. Stimulation of endothelial cell proliferation by FGF-2 in the presence of fibrinogen requires alphavbeta3. Blood 2004;104:3635-41
  • Kemp LE, Mulloy B, Gherardi E. Signalling by HGF/SF and Met: the role of heparin sulphate co-receptors. Biochem Soc Trans 2006;34:414-7
  • 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. Clin Oncol 2008;26:5610-7
  • Borgström P, Hillan KJ, Sriramarao P, Ferrara N. Complete inhibition of angiogenesis and growth of microtumors by anti-vascular endothelial growth factor neutralizing antibody: novel concepts of angiostatic therapy from intravital videomicroscopy. Cancer Res 1996;56:4032-9
  • Presta LG, Chen H, O'Connor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997;57:4593-9
  • Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335-42
  • Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007;25:1539-44
  • 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;355:2542-50
  • Miller KD, Chap LI, Holmes FA, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 2005;23:792-9
  • Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007;357:2666-76
  • Holash J, Davis S, Papadopoulos N, et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA 2002;99:11393-8
  • Levine AM, Tulpule A, Quinn DI, et al. Phase I study of antisense oligonucleotide against vascular endothelial growth factor: decrease in plasma vascular endothelial growth factor with potential clinical efficacy. J Clin Oncol 2006;24:1712-9
  • Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356:2271-81
  • Patyna S, Laird AD, Mendel DB, et al. SU14813: a novel multiple receptor tyrosine kinase inhibitor with potent antiangiogenic and antitumor activity. Mol Cancer Ther 2006;5:1774-82
  • Wiesener MS, Münchenhagen PM, Berger I, et al. Constitutive activation of hypoxia-inducible genes related to overexpression of hypoxia-inducible factor-1alpha in clear cell renal carcinomas. Cancer Res 2001;61:5215-22
  • Reddy K. Phase III study of sunitinib malate (SU11248) versus interferon-alpha as first-line treatment in patients with metastatic renal cell carcinoma. Clin Genitourin Cancer 2006;5:23-5
  • Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006;368:1329-38
  • Adams VR, Leggas M. Sunitinib malate for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors. Clin Ther 2007;29:1338-53
  • Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004;64:7099-109
  • Escudier B, Szczylik C, Hutson TE, et al. Randomized phase III trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol 2009;27:1280-9
  • Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-90
  • Heath VL, Bicknell R. Anticancer strategies involving the vasculature. Nat Rev Clin Oncol 2009;6:395-404
  • Xue Y, Religa P, Cao R, et al. Anti-VEGF agents confer survival advantages to tumor-bearing mice by improving cancer-associated systemic syndrome. Proc Natl Acad Sci USA 2008;105:18513-8
  • Puccio M, Nathanson L. The cancer cachexia syndrome. Semin Oncol 1997;24:277-87
  • Goldstein NI, Prewett M, Zuklys K, et al. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin Cancer Res 1995;1:1311-8
  • Saltz LB, Meropol NJ, Loehrer PJ Sr, et al. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 2004;22:1201-8
  • Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004;351:337-45
  • Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006;354:567-78
  • Foon KA, Yang XD, Weiner LM, et al. Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys 2004;58:984-90
  • Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 2007;25:1658-64
  • Pollack VA, Savage DM, Baker DA, et al. Inhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in human carcinomas with CP-358,774: dynamics of receptor inhibition in situ and antitumor effects in athymic mice. J Pharmacol Exp Ther 1999;291:739-48
  • Pore N, Jiang Z, Gupta A, et al. EGFR tyrosine kinase inhibitors decrease VEGF expression by both hypoxia-inducible factor (HIF)-1-independent and HIF-1-dependent mechanisms. Cancer Res 2006;66:3197-204
  • Gatzemeier U, Pluzanska A, Szczesna A, et al. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol 2007;25:1545-52
  • Herbst RS, Prager D, Hermann R, et al. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 2005;23:5892-9
  • Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005;353:123-32
  • Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007;25:1960-6
  • Bukowski R, Cella D, Gondek K, Escudier B. Effects of sorafenib on symptoms and quality of life: results from a large randomized placebo-controlled study in renal cancer. Am J Clin Oncol 2007;30:220-7
  • Motzer RJ, Bukowski RM. Targeted therapy for metastatic renal cell carcinoma. J Clin Oncol 2006;24:5601-8
  • Kamba T, Tam BY, Hashizume H, et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol 2006;290:H560-76
  • Baffert F, Le T, Sennino B, et al. Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signalling. Am J Physiol Heart Circ Physiol 2006;290:H547-59
  • Ng M, Cunningham D. Cetuximab (Erbitux)–an emerging targeted therapy for epidermal growth factor receptor-expressing tumours. Int J Clin Pract 2004;58:970-6
  • Staton CA, Reed MW, Brown NJ. A critical analysis of current in vitro and in vivo angiogenesis assays. Int J Exp Path 2009;90:195-221
  • Mancuso MR, Davis R, Norberg SM, et al. Rapid vascular re-growth in tumors after reversal of VEGF inhibition. J Clin Invest 2006;116:2610-21
  • Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005;307:58-62
  • Tong RT, Boucher Y, Kozin SV, et al. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer Res 2004;64:3731-6
  • 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;10:145-7
  • Willett CG, Boucher Y, Duda DG, et al. Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patients. J Clin Oncol 2005;23:8136-9
  • Winkler F, Kozin SV, Tong RT, et al. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 2004;6:553-63
  • Relf M, LeJeune S, Scott PA, et al. Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res 1997;57:963-9
  • Casanovas O, Hager JH, Chun MG, Hanahan D. Incomplete inhibition of the Rb tumor suppressor pathway in the context of inactivated p53 is sufficient for pancreatic islet tumorigenesis. Oncogene 2005;24:6597-604
  • Rapisarda A, Melillo G. Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies. Drug Resist Updat 2009;12:74-80
  • Fischer C, Jonckx B, Mazzone M, et al. Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell 2007;131:463-75
  • Crawford Y, Kasman I, Yu L, 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
  • Nissen LJ, Cao R, Hedlund EM, et al. Angiogenic factors FGF2 and PDGF-BB synergistically promote murine tumor neovascularization and metastasis. J Clin Invest 2007;117:2766-77
  • Ebos JM, Lee CR, Cruz-Munoz W, et al. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 2009;15:232-9
  • Pàez-Ribes M, Allen E, Hudock J, et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 2009;15:220-31
  • Brahimi-Horn MC, Chiche J, Pouysségur J. Hypoxia and cancer. J Mol Med 2007;85:1301-7
  • Loges S, Mazzone M, Hohensinner P, Carmeliet P. Silencing or fueling metastasis with VEGF inhibitors: antiangiogenesis revisited. Cancer Cell 2009;15:167-70
  • Yu JL, Rak JW, Coomber BL, et al. Effect of p53 status on tumor response to antiangiogenic therapy. Science 2002;295:1526-8
  • Ince WL, Jubb AM, Holden SN, et al. Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab. J Natl Cancer Inst 2005;97:981-9
  • LeCouter J, Kowalski J, Foster J, et al. Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature 2001;412:877-84
  • Dome B, Timar J, Ladanyi A, et al. Circulating endothelial cells, bone marrow-derived endothelial progenitor cells and proangiogenic hematopoietic cells in cancer: From biology to therapy. Crit Rev Oncol Hematol 2009;69:108-24
  • Shojaei F, Singh M, Thompson JD, Ferrara N. Role of Bv8 in neutrophil-dependent angiogenesis in a transgenic model of cancer progression. Proc Natl Acad Sci USA 2008;105:2640-5
  • Nozawa H, Chiu C, Hanahan D. Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis. Proc Natl Acad Sci USA 2006;103:12493-8
  • Soker S, Gollamudi-Payne S, Fidder H, et al. Inhibition of vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation by a peptide corresponding to the exon 7-encoded domain of VEGF165. J Biol Chem 1997;272:31582-8
  • 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;11:53-67
  • Cao Y. Positive and negative modulation of angiogenesis by VEGFR1 ligands. Sci Signal 2009;2:re1
  • Shibuya M, Claesson-Welsh L. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp Cell Res 2006;312:549-60
  • Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 200;8:592-603
  • Saltz LB, Lenz HJ, Kindler HL, et al. Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. J Clin Oncol 2007;25:4557-61
  • Herbst RS, O'Neill VJ, Fehrenbacher L, et al. Phase II study of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non small-cell lung cancer. J Clin Oncol 2007;25:4743-50
  • Tol J, Koopman M, Cats A, et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 2009;360:563-72
  • Ottewell PD, Mönkkönen H, Jones M, et al. Antitumor effects of doxorubicin followed by zoledronic acid in a mouse model of breast cancer. J Natl Cancer Inst 2008;100:1167-78
  • Powis G, Kirkpatrick L. Hypoxia inducible factor-1alpha as a cancer drug target. Mol Cancer Ther 2004;3:647-54
  • Lush RM, Figg WD, Pluda JM, et al. A phase I study of pentosan polysulfate sodium in patients with advanced malignancies. Ann Oncol 1996;7:939-44
  • Pilepich MV, Paulus R, St Clair W, et al. Phase III study of pentosanpolysulfate (PPS) in treatment of gastrointestinal tract sequelae of radiotherapy. Am J Clin Oncol 2006;29:132-7
  • Shiojima I, Walsh K. Role of Akt signaling in vascular homeostasis and angiogenesis. Circ Res 2002;90:1243-50
  • Su JD, Mayo LD, Donner DB, Durden DL. PTEN and phosphatidylinositol 3′-kinase inhibitors up-regulate p53 and block tumor-induced angiogenesis: evidence for an effect on the tumor and endothelial compartment. Cancer Res 2003;63:3585-92
  • Singh RP, Dhanalakshmi S, Agarwal C, Agarwal R. Silibinin strongly inhibits growth and survival of human endothelial cells via cell cycle arrest and downregulation of survivin, Akt and NF-kappaB: implications for angioprevention and antiangiogenic therapy. Oncogene 2005;24:1188-202
  • Bettuzzi S, Brausi M, Rizzi F, et al. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res 2006;66:1234-40
  • Uehara H, Kim SJ, Karashima T, et al. Effects of blocking platelet-derived growth factor-receptor signaling in a mouse model of experimental prostate cancer bone metastases. J Natl Cancer Inst 2003;95:458-70
  • Oliner J, Min H, Leal J, et al. Suppression of angiogenesis and tumor growth by selective inhibition of angiopoietin-2. Cancer Cell 2004;6:507-16
  • Miao HQ, Soker S, Feiner L, et al. Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-165. J Cell Biol 1999;146:233-42
  • Thurston G, Noguera-Troise I, Yancopoulos GD. The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth. Nat Rev Cancer 2007;7:327-31
  • Dobrzanski P, Hunter K, Jones-Bolin S, et al. Antiangiogenic and antitumor efficacy of EphA2 receptor antagonist. Cancer Res 2004;64:910-9
  • Dellapasqua S, Bertolini F, Bagnardi V, et al. Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer. J Clin Oncol 2008;26:4899-905
  • Duda DG, Cohen KS, di Tomaso E, et al. Differential CD146 expression on circulating versus tissue endothelial cells in rectal ancer patients: implications for circulating endothelial and progenitor cells as biomarkers for antiangiogenic therapy. J Clin Oncol 2006;24:1449-53
  • 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;11:83-95
  • Drevs J, Siegert P, Medinger M, et al. Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. J Clin Oncol 2007;25:3045-54
  • Wolmark N, Yothers G, O'Connell MJ, et al. A phase III trial comparing mFOLFOX6 to mFOLFOX6 plus bevacizumab in stage II or III carcinoma of the colon: results of NSABP Protocol C-08. J Clin Oncol 2009;27(18s): abstract LBA4

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.