Abstract
Angiogenesis inhibition is a promising approach to fight cancer. This strategy offers some advantages in comparison with conventional drugs, such as the inhibition of single vessels that can induce the death of many tumor cells. Moreover, this therapy can be used in the treatment of a wide range of solid tumors and may produce less resistance. Since angiogenesis is a complex process, it can be inhibited at different levels. The most established therapy is the inhibition of angiogenic signaling. Vascular endothelial growth factor (VEGF) pathway is the most important signaling pathway in the angiogenesis process, and for this reason, many inhibitors have been developed to block the action of VEGF or its receptors, VEGFRs. Another approach is the inhibition of endothelial progenitor cells (EPCs), mobilized from the bone marrow to the tumor site in hypoxia conditions, which contribute to the formation of new blood vessels and the pre-metastatic niche. The interaction between extracellular matrix and endothelial cells is very important during angiogenesis, so the inhibition of this interaction produces anti-angiogenic effects. An alternative strategy is based in the regression of preexisting tumor vasculature, which presents abnormalities in the structure and function in comparison with normal vessels. In this case, vascular-disrupting agents (VDAs) can cease the blood flow within minutes and lead to the formation of central necrosis. Finally, tumor vessel normalization produced after anti-angiogenic therapies may reduce the metastatic dissemination and improve delivery of drugs to the tumor.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Ahn JB, Rha SY, Shin SJ, Jeung HC, Kim TS, Zhang X, Park KH, Noh SH, Roh JK, Chung HC (2010) Circulating endothelial progenitor cells (EPC) for tumor vasculogenesis in gastric cancer patients. Cancer Lett 288(1):124–132. https://doi.org/10.1016/j.canlet.2009.06.031. S0304-3835(09)00457-1 [pii]
Algire GH, Chalkley HW (1945) Vascular reactions of normal and malignant tissues in vivo I. Vascular reactions of mice to wounds and to normal and neoplastic transplants. J Natl Cancer Inst 6:73–85
Andrea TH, Frank L, Chad M, Hans-Peter G (2013) Identification and development of vascular disrupting agents: natural products that interfere with tumor growth. In: Natural products and cancer drug discovery, Cancer drug discovery and development. Springer, New York, pp 17–38. https://doi.org/10.1007/978-1-4614-4654-5_2
Baffert F, Le T, Sennino B, Thurston G, Kuo CJ, Hu-Lowe D, McDonald DM (2006) Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling. Am J Physiol Heart Circ Physiol 290(2):H547–H559. https://doi.org/10.1152/ajpheart.00616.2005. 00616.2005 [pii]
Baguley BC, Siemann DW (2010) Temporal aspects of the action of ASA404 (vadimezan; DMXAA). Expert Opin Investig Drugs 19(11):1413–1425. https://doi.org/10.1517/13543784.2010.529128
Baluk P, Hashizume H, McDonald DM (2005) Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev 15(1):102–111. https://doi.org/10.1016/j.gde.2004.12.005. S0959-437X(04)00191-1 [pii]
Beauvais DM, Ell BJ, McWhorter AR, Rapraeger AC (2009) Syndecan-1 regulates alphavbeta3 and alphavbeta5 integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor. J Exp Med 206(3):691–705. https://doi.org/10.1084/jem.20081278. jem.20081278 [pii]
Bosslet K, Straub R, Blumrich M, Czech J, Gerken M, Sperker B, Kroemer HK, Gesson JP, Koch M, Monneret C (1998) Elucidation of the mechanism enabling tumor selective prodrug monotherapy. Cancer Res 58(6):1195–1201
Brooks PC (1996) Cell adhesion molecules in angiogenesis. Cancer Metastasis Rev 15(2):187–194
Bullitt E, Ewend MG, Aylward S, Lin W, Gerig G, Joshi S, Jung I, Muller K, Smith JK (2004) Abnormal vessel tortuosity as a marker of treatment response of malignant gliomas: preliminary report. Technol Cancer Res Treat 3(6):577–584. https://doi.org/10.1177/153303460400300607
Burge M, Francesconi AB, Kotasek D, Fida R, Smith G, Wilks A, Vasey PA, Lickliter JD (2013) Phase I, pharmacokinetic and pharmacodynamic evaluation of CYT997, an orally-bioavailable cytotoxic and vascular-disrupting agent. Investig New Drugs 31(1):126–135. https://doi.org/10.1007/s10637-012-9813-y
Burger JA, Peled A (2009) CXCR4 antagonists: targeting the microenvironment in leukemia and other cancers. Leukemia 23(1):43–52. https://doi.org/10.1038/leu.2008.299. leu2008299 [pii]
Burrows FJ, Thorpe PE (1993) Eradication of large solid tumors in mice with an immunotoxin directed against tumor vasculature. Proc Natl Acad Sci USA 90(19):8996–9000
Byzova TV, Goldman CK, Pampori N, Thomas KA, Bett A, Shattil SJ, Plow EF (2000) A mechanism for modulation of cellular responses to VEGF: activation of the integrins. Mol Cell 6(4):851–860. https://doi.org/S1097-2765(05)00076-6 [pii]
Cesca M, Bizzaro F, Zucchetti M, Giavazzi R (2013) Tumor delivery of chemotherapy combined with inhibitors of angiogenesis and vascular targeting agents. Front Oncol 3:259. https://doi.org/10.3389/fonc.2013.00259
Chaplin DJ, Horsman MR, Siemann DW (2006) Current development status of small-molecule vascular disrupting agents. Curr Opin Investig Drugs 7(6):522–528
Chen CS, Tan J, Tien J (2004) Mechanotransduction at cell-matrix and cell-cell contacts. Annu Rev Biomed Eng 6:275–302. https://doi.org/10.1146/annurev.bioeng.6.040803.140040
Chung F, Liu J, Ching LM, Baguley BC (2008) Consequences of increased vascular permeability induced by treatment of mice with 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and thalidomide. Cancer Chemother Pharmacol 61(3):497–502. https://doi.org/10.1007/s00280-007-0495-7
D’Amore PA, Thompson RW (1987) Mechanisms of angiogenesis. Annu Rev Physiol 49:453–464. https://doi.org/10.1146/annurev.ph.49.030187.002321
Dark GG, Hill SA, Prise VE, Tozer GM, Pettit GR, Chaplin DJ (1997) Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature. Cancer Res 57(10):1829–1834
De Bock K, De Smet F, Leite De Oliveira R, Anthonis K, Carmeliet P (2009) Endothelial oxygen sensors regulate tumor vessel abnormalization by instructing phalanx endothelial cells. J Mol Med (Berl) 87(6):561–569. https://doi.org/10.1007/s00109-009-0482-z
De S, Razorenova O, McCabe NP, O’Toole T, Qin J, Byzova TV (2005) VEGF-integrin interplay controls tumor growth and vascularization. Proc Natl Acad Sci USA 102(21):7589–7594. https://doi.org/10.1073/pnas.0502935102. 0502935102 [pii]
DeMali KA, Wennerberg K, Burridge K (2003) Integrin signaling to the actin cytoskeleton. Curr Opin Cell Biol 15(5):572–582. https://doi.org/S0955067403001091 [pii]
Denekamp J, Hill SA, Hobson B (1983) Vascular occlusion and tumour cell death. Eur J Cancer Clin Oncol 19(2):271–275
Denekamp J, Hobson B (1982) Endothelial-cell proliferation in experimental tumours. Br J Cancer 46(5):711–720
Dickson PV, Hamner JB, Sims TL, Fraga CH, Ng CY, Rajasekeran S, Hagedorn NL, McCarville MB, Stewart CF, Davidoff AM (2007) Bevacizumab-induced transient remodeling of the vasculature in neuroblastoma xenografts results in improved delivery and efficacy of systemically administered chemotherapy. Clin Cancer Res 13(13):3942–3950. https://doi.org/10.1158/1078-0432.CCR-07-0278. 13/13/3942 [pii]
Dome B, Timar J, Dobos J, Meszaros L, Raso E, Paku S, Kenessey I, Ostoros G, Magyar M, Ladanyi A, Bogos K, Tovari J (2006) Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer. Cancer Res 66(14):7341–7347. https://doi.org/10.1158/0008-5472.CAN-05-4654. 66/14/7341 [pii]
Drake CJ, Cheresh DA, Little CD (1995) An antagonist of integrin alpha v beta 3 prevents maturation of blood vessels during embryonic neovascularization. J Cell Sci 108(Pt 7):2655–2661
Eberhard A, Kahlert S, Goede V, Hemmerlein B, Plate KH, Augustin HG (2000) Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. Cancer Res 60(5):1388–1393
Farace F, Massard C, Borghi E, Bidart JM, Soria JC (2007) Vascular disrupting therapy-induced mobilization of circulating endothelial progenitor cells. Ann Oncol 18(8):1421–1422. https://doi.org/10.1093/annonc/mdm367. 18/8/1421 [pii]
Ferrara N (1999) Molecular and biological properties of vascular endothelial growth factor. J Mol Med (Berl) 77(7):527–543
Ferrara N (2010) Pathways mediating VEGF-independent tumor angiogenesis. Cytokine Growth Factor Rev 21(1):21–26. https://doi.org/10.1016/j.cytogfr.2009.11.003. S1359-6101(09)00110-5 [pii]
Folkman J, Long DM Jr, Becker FF (1963) Growth and metastasis of tumor in organ culture. Cancer 16:453–467
Franco M, Man S, Chen L, Emmenegger U, Shaked Y, Cheung AM, Brown AS, Hicklin DJ, Foster FS, Kerbel RS (2006) 1. Cancer Res 66(7):3639–3648. https://doi.org/10.1158/0008-5472.CAN-05-3295. 66/7/3639 [pii]
Friedlander M, Brooks PC, Shaffer RW, Kincaid CM, Varner JA, Cheresh DA (1995) Definition of two angiogenic pathways by distinct alpha v integrins. Science 270(5241):1500–1502
Gan HK, Seruga B, Knox JJ (2009) Sunitinib in solid tumors. Expert Opin Investig Drugs 18(6):821–834. https://doi.org/10.1517/13543780902980171
Gazit Y, Baish JW, Safabakhsh N, Leunig M, Baxter LT, Jain RK (1997) Fractal characteristics of tumor vascular architecture during tumor growth and regression. Microcirculation 4(4):395–402
Grosios K, Loadman PM, Swaine DJ, Pettit GR, Bibby MC (2000) Combination chemotherapy with combretastatin A-4 phosphate and 5-fluorouracil in an experimental murine colon adenocarcinoma. Anticancer Res 20(1A):229–233
Gutheil JC, Campbell TN, Pierce PR, Watkins JD, Huse WD, Bodkin DJ, Cheresh DA (2000) Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal antibody to the integrin alphavbeta3. Clin Cancer Res 6(8):3056–3061
Hamzah J, Jugold M, Kiessling F, Rigby P, Manzur M, Marti HH, Rabie T, Kaden S, Grone HJ, Hammerling GJ, Arnold B, Ganss R (2008) Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature 453(7193):410–414. https://doi.org/10.1038/nature06868. nature06868 [pii]
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. https://doi.org/10.1016/j.cell.2011.02.013. S0092-8674(11)00127-9 [pii]
Hartmann JT, Haap M, Kopp HG, Lipp HP (2009) Tyrosine kinase inhibitors – a review on pharmacology, metabolism and side effects. Curr Drug Metab 10(5):470–481
Hasani A, Leighl N (2011) Classification and toxicities of vascular disrupting agents. Clin Lung Cancer 12(1):18–25. https://doi.org/10.3816/CLC.2011.n.002. S1525-7304(11)70052-3 [pii]
Hellberg C, Ostman A, Heldin CH (2010) PDGF and vessel maturation. Recent Results Cancer Res 180:103–114. https://doi.org/10.1007/978-3-540-78281-0_7
Hey T, Fiedler E, Rudolph R, Fiedler M (2005) Artificial, non-antibody binding proteins for pharmaceutical and industrial applications. Trends Biotechnol 23(10):514–522. https://doi.org/10.1016/j.tibtech.2005.07.007. S0167-7799(05)00196-4 [pii]
Hicklin DJ, Ellis LM (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23(5):1011–1027. https://doi.org/10.1200/JCO.2005.06.081. JCO.2005.06.081 [pii]
Hirsch E, Brancaccio M, Altruda F (2000) Tissue-specific KO of ECM proteins. Methods Mol Biol 139:147–178. https://doi.org/10.1385/1-59259-063-2:147. 1-59259-063-2-147 [pii]
Huang FJ, You WK, Bonaldo P, Seyfried TN, Pasquale EB, Stallcup WB (2010) Pericyte deficiencies lead to aberrant tumor vascularizaton in the brain of the NG2 null mouse. Dev Biol 344(2):1035–1046. https://doi.org/10.1016/j.ydbio.2010.06.023. S0012-1606(10)00843-2 [pii]
Huang X, Molema G, King S, Watkins L, Edgington TS, Thorpe PE (1997) Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature. Science 275(5299):547–550
Hwang R, Varner J (2004) The role of integrins in tumor angiogenesis. Hematol Oncol Clin North Am 18(5):991–1006. https://doi.org/10.1016/j.hoc.2004.09.010. S0889-8588(04)00126-1 [pii]
Hynes RO (2004) The emergence of integrins: a personal and historical perspective. Matrix Biol 23(6):333–340. https://doi.org/10.1016/j.matbio.2004.08.001. S0945-053X(04)00098-8 [pii]
Ide AG, Baker NH, Warren SL (1939) Vascularization of the Brown-Pearce rabbit epithelioma transplant as seen in the transparent chamber. Am J Radiol 42:891–899
Inai T, Mancuso M, Hashizume H, Baffert F, Haskell A, Baluk P, Hu-Lowe DD, Shalinsky DR, Thurston G, Yancopoulos GD, McDonald DM (2004) Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol 165(1):35–52. https://doi.org/10.1016/S0002-9440(10)63273-7. S0002-9440(10)63273-7 [pii]
Innocenti F, Ramirez J, Obel J, Xiong J, Mirkov S, Chiu YL, Katz DA, Carr RA, Zhang W, Das S, Adjei A, Moyer AM, Chen PX, Krivoshik A, Medina D, Gordon GB, Ratain MJ, Sahelijo L, Weinshilboum RM, Fleming GF, Bhathena A (2013) Preclinical discovery of candidate genes to guide pharmacogenetics during phase I development: the example of the novel anticancer agent ABT-751. Pharmacogenet Genomics 23(7):374–381. https://doi.org/10.1097/FPC.0b013e3283623e81
Jain RK (1988) Determinants of tumor blood flow: a review. Cancer Res 48(10):2641–2658
Jain RK (2001) Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 7(9):987–989. https://doi.org/10.1038/nm0901-987. nm0901-987 [pii]
Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307(5706):58–62. https://doi.org/10.1126/science.1104819. 307/5706/58 [pii]
Jin F, Brockmeier U, Otterbach F, Metzen E (2012) New insight into the SDF-1/CXCR4 axis in a breast carcinoma model: hypoxia-induced endothelial SDF-1 and tumor cell CXCR4 are required for tumor cell intravasation. Mol Cancer Res 10(8):1021–1031. https://doi.org/10.1158/1541-7786.MCR-11-0498. 1541-7786.MCR-11-0498 [pii]
Jordan MA, Wilson L (2004) Microtubules as a target for anticancer drugs. Nat Rev Cancer 4(4):253–265. https://doi.org/10.1038/nrc1317. nrc1317 [pii]
Jung YD, Ahmad SA, Liu W, Reinmuth N, Parikh A, Stoeltzing O, Fan F, Ellis LM (2002) The role of the microenvironment and intercellular cross-talk in tumor angiogenesis. Semin Cancer Biol 12(2):105–112. https://doi.org/10.1006/scbi.2001.0418. S1044579X01904183 [pii]
Kalluri R (2003) Basement membranes: structure, assembly and role in tumour angiogenesis. Nat Rev Cancer 3(6):422–433. https://doi.org/10.1038/nrc1094. nrc1094 [pii]
Kamba T, McDonald DM (2007) Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer 96(12):1788–1795. https://doi.org/10.1038/sj.bjc.6603813. 6603813 [pii]
Kashiwagi S, Tsukada K, Xu L, Miyazaki J, Kozin SV, Tyrrell JA, Sessa WC, Gerweck LE, Jain RK, Fukumura D (2008) Perivascular nitric oxide gradients normalize tumor vasculature. Nat Med 14(3):255–257. https://doi.org/10.1038/nm1730. nm1730 [pii]
Kelly RJ, Darnell C, Rixe O (2010) Target inhibition in antiangiogenic therapy a wide spectrum of selectivity and specificity. Cancer J 16(6):635–642. https://doi.org/10.1097/PPO.0b013e3181ff37cf. 00130404-201011000-00014 [pii]
Kerbel R, Folkman J (2002) Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2(10):727–739. https://doi.org/10.1038/nrc905. nrc905 [pii]
Kienast Y, von Baumgarten L, Fuhrmann M, Klinkert WE, Goldbrunner R, Herms J, Winkler F (2010) Real-time imaging reveals the single steps of brain metastasis formation. Nat Med 16(1):116–122. https://doi.org/10.1038/nm.2072. nm.2072 [pii]
Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362(6423):841–844. https://doi.org/10.1038/362841a0
Kim S, Harris M, Varner JA (2000) Regulation of integrin alpha vbeta 3-mediated endothelial cell migration and angiogenesis by integrin alpha5beta1 and protein kinase a. J Biol Chem 275(43):33920–33928. https://doi.org/10.1074/jbc.M003668200. M003668200 [pii]
Kraling BM, Razon MJ, Boon LM, Zurakowski D, Seachord C, Darveau RP, Mulliken JB, Corless CL, Bischoff J (1996) E-selectin is present in proliferating endothelial cells in human hemangiomas. Am J Pathol 148(4):1181–1191
Krause DS, Van Etten RA (2005) Tyrosine kinases as targets for cancer therapy. N Engl J Med 353(2):172–187. https://doi.org/10.1056/NEJMra044389. 353/2/172 [pii]
Lippert JW 3rd (2007) Vascular disrupting agents. Bioorg Med Chem 15(2):605–615. https://doi.org/10.1016/j.bmc.2006.10.020. S0968-0896(06)00853-4 [pii]
Lorusso PM, Boerner SA, Hunsberger S (2011) Clinical development of vascular disrupting agents: what lessons can we learn from ASA404? J Clin Oncol 29(22):2952–2955. https://doi.org/10.1200/JCO.2011.36.1311
Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, Chadburn A, Heissig B, Marks W, Witte L, Wu Y, Hicklin D, Zhu Z, Hackett NR, Crystal RG, Moore MA, Hajjar KA, Manova K, Benezra R, Rafii S (2001) Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 7(11):1194–1201. https://doi.org/10.1038/nm1101-1194. nm1101-1194 [pii]
Marneros AG, Olsen BR (2005) Physiological role of collagen XVIII and endostatin. FASEB J 19(7):716–728. https://doi.org/10.1096/fj.04-2134rev. 19/7/716 [pii]
Masson V, de la Ballina LR, Munaut C, Wielockx B, Jost M, Maillard C, Blacher S, Bajou K, Itoh T, Itohara S, Werb Z, Libert C, Foidart JM, Noel A (2005) Contribution of host MMP-2 and MMP-9 to promote tumor vascularization and invasion of malignant keratinocytes. FASEB J 19(2):234–236. https://doi.org/10.1096/fj.04-2140fje. 04-2140fje [pii]
Matsumura T, Wolff K, Petzelbauer P (1997) Endothelial cell tube formation depends on cadherin 5 and CD31 interactions with filamentous actin. J Immunol 158(7):3408–3416
Matsusaka S, Mishima Y, Suenaga M, Terui Y, Kuniyoshi R, Mizunuma N, Hatake K (2011) Circulating endothelial progenitors and CXCR4-positive circulating endothelial cells are predictive markers for bevacizumab. Cancer 117(17):4026–4032. https://doi.org/10.1002/cncr.25977
Mazzone M, Dettori D, Leite de Oliveira R, Loges S, Schmidt T, Jonckx B, Tian YM, Lanahan AA, Pollard P, Ruiz de Almodovar C, De Smet F, Vinckier S, Aragones J, Debackere K, Luttun A, Wyns S, Jordan B, Pisacane A, Gallez B, Lampugnani MG, Dejana E, Simons M, Ratcliffe P, Maxwell P, Carmeliet P (2009) Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization. Cell 136(5):839–851. https://doi.org/10.1016/j.cell.2009.01.020. S0092-8674(09)00068-3 [pii]
McCarthy AD, Uemura T, Etcheverry SB, Cortizo AM (2004) Advanced glycation endproducts interefere with integrin-mediated osteoblastic attachment to a type-I collagen matrix. Int J Biochem Cell Biol 36(5):840–848. https://doi.org/10.1016/j.biocel.2003.09.006. S1357272503003169 [pii]
Mitrus I, Sochanik A, Cichon T, Szala S (2009) Combination of combretastatin A4 phosphate and doxorubicin-containing liposomes affects growth of B16-F10 tumors. Acta Biochim Pol 56(1):161–165. https://doi.org/20091765 [pii]
Moccia F, Zuccolo E, Poletto V, Cinelli M, Bonetti E, Guerra G, Rosti V (2015) Endothelial progenitor cells support tumour growth and metastatisation: implications for the resistance to anti-angiogenic therapy. Tumour Biol 36(9):6603–6614. https://doi.org/10.1007/s13277-015-3823-2
Mohle R, Bautz F, Rafii S, Moore MA, Brugger W, Kanz L (1998) The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1. Blood 91(12):4523–4530
Moore MA (2002) Putting the neo into neoangiogenesis. J Clin Invest 109(3):313–315. https://doi.org/10.1172/JCI14940
Morikawa S, Baluk P, Kaidoh T, Haskell A, Jain RK, McDonald DM (2002) Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. Am J Pathol 160(3):985–1000. https://doi.org/10.1016/S0002-9440(10)64920-6. S0002-9440(10)64920-6 [pii]
Mott JD, Werb Z (2004) Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 16(5):558–564. https://doi.org/10.1016/j.ceb.2004.07.010. S0955-0674(04)00109-7 [pii]
Mould AP, Humphries MJ (2004) Regulation of integrin function through conformational complexity: not simply a knee-jerk reaction? Curr Opin Cell Biol 16(5):544–551. https://doi.org/10.1016/j.ceb.2004.07.003. S0955-0674(04)00098-5 [pii]
Nagy JA, Chang SH, Shih SC, Dvorak AM, Dvorak HF (2010) Heterogeneity of the tumor vasculature. Semin Thromb Hemost 36(3):321–331. https://doi.org/10.1055/s-0030-1253454
Nelson CM, Chen CS (2003) VE-cadherin simultaneously stimulates and inhibits cell proliferation by altering cytoskeletal structure and tension. J Cell Sci 116(Pt 17):3571–3581. https://doi.org/10.1242/jcs.00680. jcs.00680 [pii]
Nguyen M, Strubel NA, Bischoff J (1993) A role for sialyl Lewis-X/a glycoconjugates in capillary morphogenesis. Nature 365(6443):267–269. https://doi.org/10.1038/365267a0
Noel A, Maillard C, Rocks N, Jost M, Chabottaux V, Sounni NE, Maquoi E, Cataldo D, Foidart JM (2004) Membrane associated proteases and their inhibitors in tumour angiogenesis. J Clin Pathol 57(6):577–584
Nowak K, Rafat N, Belle S, Weiss C, Hanusch C, Hohenberger P, Beck G (2010) Circulating endothelial progenitor cells are increased in human lung cancer and correlate with stage of disease. Eur J Cardiothorac Surg 37(4):758–763. https://doi.org/10.1016/j.ejcts.2009.10.002. S1010-7940(09)00977-4 [pii]
Ono M, Kosaka N, Tominaga N, Yoshioka Y, Takeshita F, Takahashi RU, Yoshida M, Tsuda H, Tamura K, Ochiya T (2014) Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells. Sci Signal 7(332):ra63. https://doi.org/10.1126/scisignal.2005231. 7/332/ra63 [pii]
Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, Oz MC, Hicklin DJ, Witte L, Moore MA, Rafii S (2000) Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 95(3):952–958
Petitclerc E, Boutaud A, Prestayko A, Xu J, Sado Y, Ninomiya Y, Sarras MP Jr, Hudson BG, Brooks PC (2000) New functions for non-collagenous domains of human collagen type IV. Novel integrin ligands inhibiting angiogenesis and tumor growth in vivo. J Biol Chem 275(11):8051–8061
Porcu E, Viola G, Bortolozzi R, Persano L, Mitola S, Ronca R, Presta M, Romagnoli R, Baraldi PG, Basso G (2013) TR-644 a novel potent tubulin binding agent induces impairment of endothelial cells function and inhibits angiogenesis. Angiogenesis 16(3):647–662. https://doi.org/10.1007/s10456-013-9343-z
Pytela R, Pierschbacher MD, Ruoslahti E (1985) Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor. Cell 40(1):191–198. https://doi.org/0092-8674(85)90322-8 [pii]
Ravelli C, Mitola S, Corsini M, Presta M (2013) Involvement of alphavbeta3 integrin in gremlin-induced angiogenesis. Angiogenesis 16(1):235–243. https://doi.org/10.1007/s10456-012-9309-6
Rey S, Semenza GL (2010) Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodelling. Cardiovasc Res 86(2):236–242. https://doi.org/10.1093/cvr/cvq045. cvq045 [pii]
Risau W (1997) Mechanisms of angiogenesis. Nature 386(6626):671–674. https://doi.org/10.1038/386671a0
Roberts ZJ, Goutagny N, Perera PY, Kato H, Kumar H, Kawai T, Akira S, Savan R, van Echo D, Fitzgerald KA, Young HA, Ching LM, Vogel SN (2007) The chemotherapeutic agent DMXAA potently and specifically activates the TBK1-IRF-3 signaling axis. J Exp Med 204(7):1559–1569. https://doi.org/10.1084/jem.20061845. https://doi.org/jem.20061845 [pii]
Schwartz EL (2009) Antivascular actions of microtubule-binding drugs. Clin Cancer Res 15(8):2594–2601. https://doi.org/10.1158/1078-0432.CCR-08-2710. 1078-0432.CCR-08-2710 [pii]
Seiki M, Koshikawa N, Yana I (2003) Role of pericellular proteolysis by membrane-type 1 matrix metalloproteinase in cancer invasion and angiogenesis. Cancer Metastasis Rev 22(2–3):129–143
Senger DR, Claffey KP, Benes JE, Perruzzi CA, Sergiou AP, Detmar M (1997) Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha1beta1 and alpha2beta1 integrins. Proc Natl Acad Sci USA 94(25):13612–13617
Serini G, Valdembri D, Bussolino F (2006) Integrins and angiogenesis: a sticky business. Exp Cell Res 312(5):651–658. https://doi.org/10.1016/j.yexcr.2005.10.020. S0014-4827(05)00499-4 [pii]
Shih T, Lindley C (2006) Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies. Clin Ther 28(11):1779–1802. https://doi.org/10.1016/j.clinthera.2006.11.015. S0149-2918(06)00285-2 [pii]
Short SM, Derrien A, Narsimhan RP, Lawler J, Ingber DE, Zetter BR (2005) Inhibition of endothelial cell migration by thrombospondin-1 type-1 repeats is mediated by beta1 integrins. J Cell Biol 168(4):643–653. https://doi.org/10.1083/jcb.200407060. https://doi.org/jcb.200407060 [pii]
Shrimali RK, Yu Z, Theoret MR, Chinnasamy D, Restifo NP, Rosenberg SA (2010) Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer. Cancer Res 70(15):6171–6180. https://doi.org/10.1158/0008-5472.CAN-10-0153. 0008-5472.CAN-10-0153 [pii]
Siemann DW, Bibby MC, Dark GG, Dicker AP, Eskens FA, Horsman MR, Marme D, Lorusso PM (2005) Differentiation and definition of vascular-targeted therapies. Clin Cancer Res 11(2 Pt 1):416–420. https://doi.org/11/2/416 [pii]
Sorensen AG, Batchelor TT, Zhang WT, Chen PJ, Yeo P, Wang M, Jennings D, Wen PY, Lahdenranta J, Ancukiewicz M, di Tomaso E, Duda DG, Jain RK (2009) A “vascular normalization index” as potential mechanistic biomarker to predict survival after a single dose of cediranib in recurrent glioblastoma patients. Cancer Res 69(13):5296–5300. https://doi.org/10.1158/0008-5472.CAN-09-0814. 0008-5472.CAN-09-0814 [pii]
Stupack DG, Cheresh DA (2004) Integrins and angiogenesis. Curr Top Dev Biol 64:207–238. https://doi.org/10.1016/S0070-2153(04)64009-9. S0070215304640099 [pii]
Sullivan R, Graham CH (2007) Hypoxia-driven selection of the metastatic phenotype. Cancer Metastasis Rev 26(2):319–331. https://doi.org/10.1007/s10555-007-9062-2
Tang N, Wang L, Esko J, Giordano FJ, Huang Y, Gerber HP (2016) Loss of HIF-1α in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis. Cancer Cell 6:485–495
Taylor M, Billiot F, Marty V, Rouffiac V, Cohen P, Tournay E, Opolon P, Louache F, Vassal G, Laplace-Builhe C, Vielh P, Soria JC, Farace F (2012) Reversing resistance to vascular-disrupting agents by blocking late mobilization of circulating endothelial progenitor cells. Cancer Discov 2(5):434–449. https://doi.org/10.1158/2159-8290.CD-11-0171. 2159-8290.CD-11-0171 [pii]
Thorpe PE, Chaplin DJ, Blakey DC (2003) The first international conference on vascular targeting: meeting overview. Cancer Res 63(5):1144–1147
Thurston G, Suri C, Smith K, McClain J, Sato TN, Yancopoulos GD, McDonald DM (1999) Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science 286(5449):2511–2514. https://doi.org/8121 [pii]
Tijono SM, Guo K, Henare K, Palmer BD, Wang LC, Albelda SM, Ching LM (2013) Identification of human-selective analogues of the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA). Br J Cancer 108(6):1306–1315. https://doi.org/10.1038/bjc.2013.101. bjc2013101 [pii]
Trikha M, Zhou Z, Nemeth JA, Chen Q, Sharp C, Emmell E, Giles-Komar J, Nakada MT (2004) CNTO 95, a fully human monoclonal antibody that inhibits alphav integrins, has antitumor and antiangiogenic activity in vivo. Int J Cancer 110(3):326–335. https://doi.org/10.1002/ijc.20116
Tugues S, Honjo S, Konig C, Padhan N, Kroon J, Gualandi L, Li X, Barkefors I, Thijssen VL, Griffioen AW, Claesson-Welsh L (2013) Tetraspanin CD63 promotes vascular endothelial growth factor receptor 2-beta1 integrin complex formation, thereby regulating activation and downstream signaling in endothelial cells in vitro and in vivo. J Biol Chem 288(26):19060–19071. https://doi.org/10.1074/jbc.M113.468199. M113.468199 [pii]
Verweij J, Sleijfer S (2013) Pazopanib, a new therapy for metastatic soft tissue sarcoma. Expert Opin Pharmacother 14(7):929–935. https://doi.org/10.1517/14656566.2013.780030
Vincent L, Kermani P, Young LM, Cheng J, Zhang F, Shido K, Lam G, Bompais-Vincent H, Zhu Z, Hicklin DJ, Bohlen P, Chaplin DJ, May C, Rafii S (2005) Combretastatin A4 phosphate induces rapid regression of tumor neovessels and growth through interference with vascular endothelial-cadherin signaling. J Clin Invest 115(11):2992–3006. https://doi.org/10.1172/JCI24586
Welford AF, Biziato D, Coffelt SB, Nucera S, Fisher M, Pucci F, Di Serio C, Naldini L, De Palma M, Tozer GM, Lewis CE (2011) TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice. J Clin Invest 121(5):1969–1973. https://doi.org/10.1172/JCI44562. 44562 [pii]
Wilczynski J, Duechler M, Czyz M (2011) Targeting NF-kappaB and HIF-1 pathways for the treatment of cancer: part II. Arch Immunol Ther Exp 59(4):301–307. https://doi.org/10.1007/s00005-011-0132-3
Wildiers H, Guetens G, De Boeck G, Verbeken E, Landuyt B, Landuyt W, de Bruijn EA, van Oosterom AT (2003) Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11. Br J Cancer 88(12):1979–1986. https://doi.org/10.1038/sj.bjc.6601005. 6601005 [pii]
Willett CG, Duda DG, di Tomaso E, Boucher Y, Ancukiewicz M, Sahani DV, Lahdenranta J, Chung DC, Fischman AJ, Lauwers GY, Shellito P, Czito BG, Wong TZ, Paulson E, Poleski M, Vujaskovic Z, Bentley R, Chen HX, Clark JW, Jain RK (2009) Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol 27(18):3020–3026. https://doi.org/10.1200/JCO.2008.21.1771. JCO.2008.21.1771 [pii]
Wu XY, Ma W, Gurung K, Guo CH (2013) Mechanisms of tumor resistance to small-molecule vascular disrupting agents: treatment and rationale of combination therapy. J Formos Med Assoc 112(3):115–124. https://doi.org/10.1016/j.jfma.2012.09.017. S0929-6646(12)00474-3 [pii]
Xiong JP, Stehle T, Goodman SL, Arnaout MA (2003) Integrins, cations and ligands: making the connection. J Thromb Haemost 1(7):1642–1654. doi:277 [pii]
Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349(5):427–434. https://doi.org/10.1056/NEJMoa021491. 349/5/427 [pii]
Yang JT, Rayburn H, Hynes RO (1995) Cell adhesion events mediated by alpha 4 integrins are essential in placental and cardiac development. Development 121(2):549–560
Yonenaga Y, Mori A, Onodera H, Yasuda S, Oe H, Fujimoto A, Tachibana T, Imamura M (2005) Absence of smooth muscle actin-positive pericyte coverage of tumor vessels correlates with hematogenous metastasis and prognosis of colorectal cancer patients. Oncology 69(2):159–166. https://doi.org/10.1159/000087840. 87840 [pii]
Zhao L, Ching LM, Kestell P, Kelland LR, Baguley BC (2005) Mechanisms of tumor vascular shutdown induced by 5,6-dimethylxanthenone-4-acetic acid (DMXAA): increased tumor vascular permeability. Int J Cancer 116(2):322–326. https://doi.org/10.1002/ijc.21005
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this entry
Cite this entry
Pons-Cursach, R., Casanovas, O. (2019). Mechanisms of Anti-angiogenic Therapy. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-33673-2_2
Download citation
DOI: https://doi.org/10.1007/978-3-319-33673-2_2
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-33671-8
Online ISBN: 978-3-319-33673-2
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences