Skip to main content
SpringerLink
Log in
Book cover

From Local Invasion to Metastatic Cancer pp 11–21Cite as

Vascular Endothelial Growth Factor: Basic Biology and Clinical Applications

  • Chapter
  • First Online:

  • 939 Accesses

Part of the book series: Current Clinical Oncology ((CCO))

Abstract

Vascular endothelial growth factor (VEGF)-A is a well-characterized angiogenic factor involved in physiological and pathological growth of blood vessels. The homologous tyrosine kinases VEGFR-1 and VEGFR-2 are the main VEGF-A receptors. Much evidence indicates that VEGF-A is important in tumor angiogenesis. Humanized anti-VEGF-A monoclonal antibodies and two small-molecule inhibitors of VEGF receptor signaling have been approved by the US Food and Drug Administration (FDA) for cancer therapy. Furthermore, VEGF-A is implicated in intraocular neovascularization associated with active proliferative retinopathies and the neovascular form of age-related macular degeneration (AMD).

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Folkman J, Klagsbrun M. Angiogenic factors. Science 1987;235:442–7.

    Article  PubMed  CAS  Google Scholar 

  2. Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J. Vascular-specific growth factors and blood vessel formation. Nature 2000;407(6801):242–8.

    Article  PubMed  CAS  Google Scholar 

  3. Sund M, Hamano Y, Sugimoto H, et al. Function of endogenous inhibitors of angiogenesis as endothelium-specific tumor suppressors. Proc Natl Acad Sci USA 2005;102(8):2934–9.

    Article  PubMed  CAS  Google Scholar 

  4. Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer 2002;2(10):795–803.

    Article  PubMed  CAS  Google Scholar 

  5. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9:669–76.

    Article  PubMed  CAS  Google Scholar 

  6. Alitalo K, Tammela T, Petrova TV. Lymphangiogenesis in development and human disease. Nature 2005;438:946–53.

    Article  PubMed  CAS  Google Scholar 

  7. Ferrara N, Mass RD, Campa C, Kim R. Targeting VEGF-A to treat cancer and age-related macular degeneration. Annu Rev Med 2007;58:491–504.

    Article  PubMed  CAS  Google Scholar 

  8. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983;219:983–5.

    Article  PubMed  CAS  Google Scholar 

  9. Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 1989;161(2):851–8.

    Article  PubMed  CAS  Google Scholar 

  10. Connolly DT, Olander JV, Heuvelman D, et al. Human vascular permeability factor. Isolation from U937 cells. J Biol Chem 1989;264:20017–24.

    PubMed  CAS  Google Scholar 

  11. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989;246(4935):1306–9.

    Article  PubMed  CAS  Google Scholar 

  12. Keck PJ, Hauser SD, Krivi G, et al. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 1989;246(4935):1309–12.

    Article  PubMed  CAS  Google Scholar 

  13. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004;25:581–611.

    Article  PubMed  CAS  Google Scholar 

  14. Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 2002;20(21):4368–80.

    Article  PubMed  CAS  Google Scholar 

  15. Ferrara N, Carver Moore K, Chen H, et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996;380(6573):439–42.

    Article  PubMed  CAS  Google Scholar 

  16. Gerber HP, Hillan KJ, Ryan AM, et al. VEGF is required for growth and survival in neonatal mice. Development 1999;126:1149–59.

    PubMed  CAS  Google Scholar 

  17. Malik AK, Baldwin ME, Peale F, et al. Redundant roles of VEGF-B and PlGF during selective VEGF-A blockade in mice. Blood 2006;107:550–7.

    Article  PubMed  CAS  Google Scholar 

  18. Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N. VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 1999;5:623–8.

    Article  PubMed  CAS  Google Scholar 

  19. Ferrara N, Chen H, Davis-Smyth T, et al. Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nat Med 1998;4:336–40.

    Article  PubMed  CAS  Google Scholar 

  20. Alon T, Hemo I, Itin A, Pe’er J, Stone J, Keshet E. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1995;1(10):1024–8.

    Article  PubMed  CAS  Google Scholar 

  21. Gerber HP, Dixit V, Ferrara N. Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J Biol Chem 1998;273:13313–6.

    Article  PubMed  CAS  Google Scholar 

  22. Gerber HP, McMurtrey A, Kowalski J, et al. VEGF regulates endothelial cell survival by the PI3-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem 1998;273:30336–43.

    Article  PubMed  CAS  Google Scholar 

  23. Benjamin LE, Golijanin D, Itin A, Pode D, Keshet E. Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal [see comments]. J Clin Invest 1999;103(2):159–65.

    Article  PubMed  CAS  Google Scholar 

  24. Tran J, Master Z, Yu JL, Rak J, Dumont DJ, Kerbel RS. A role for survivin in chemoresistance of endothelial cells mediated by VEGF. Proc Natl Acad Sci USA 2002;99(7):4349–54.

    Article  PubMed  CAS  Google Scholar 

  25. Carmeliet P. Angiogenesis in life, disease and medicine. Nature 2005;438(7070):932–6.

    Article  PubMed  CAS  Google Scholar 

  26. Clauss M, Gerlach M, Gerlach H, et al. Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 1990;172(6):1535–45.

    Article  PubMed  CAS  Google Scholar 

  27. Barleon B, Sozzani S, Zhou D, Weich HA, Mantovani A, Marme D. Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 1996;87(8):3336–43.

    PubMed  CAS  Google Scholar 

  28. Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol 1991;5(12):1806–14.

    Article  PubMed  CAS  Google Scholar 

  29. Tischer E, Mitchell R, Hartman T, et al. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 1991;266(18):11947–54.

    PubMed  CAS  Google Scholar 

  30. Plouet J, Schilling J, Gospodarowicz D. Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT20 cells. EMBO J 1989;8:3801–8.

    PubMed  CAS  Google Scholar 

  31. Houck KA, Leung DW, Rowland AM, Winer J, Ferrara N. Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem 1992;267(36):26031–7.

    PubMed  CAS  Google Scholar 

  32. Park JE, Keller G-A, Ferrara N. The vascular endothelial growth factor isoforms (VEGF): differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. Mol Biol Cell 1993;4:1317–26.

    PubMed  CAS  Google Scholar 

  33. Keyt BA, Berleau LT, Nguyen HV, et al. The carboxyl-terminal domain (111-165) of vascular endothelial growth factor is critical for its mitogenic potency. J Biol Chem 1996;271(13):7788–95.

    Article  PubMed  CAS  Google Scholar 

  34. Lee S, Jilani SM, Nikolova GV, Carpizo D, Iruela-Arispe ML. Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. J Cell Biol 2005;169(4):681–91.

    Article  PubMed  CAS  Google Scholar 

  35. Shibuya M, Yamaguchi S, Yamane A, et al. Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase (flt) closely related to the fms family. Oncogene 1990;8:519–27.

    Google Scholar 

  36. Terman BI, Dougher-Vermazen M, Carrion ME, et al. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun 1992;187(3):1579–86.

    Article  PubMed  CAS  Google Scholar 

  37. de Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 1992;255(5047):989–91.

    Article  PubMed  Google Scholar 

  38. Park JE, Chen HH, Winer J, Houck KA, Ferrara N. Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem 1994;269(41):25646–54.

    PubMed  CAS  Google Scholar 

  39. Olofsson B, Korpelainen E, Pepper MS, et al. Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc Natl Acad Sci USA 1998;95(20):11709–14.

    Article  PubMed  CAS  Google Scholar 

  40. LeCouter J, Moritz DR, Li B, et al. Angiogenesis-independent endothelial protection of liver: role of VEGFR-1. Science 2003;299:890–3.

    Article  PubMed  CAS  Google Scholar 

  41. Hiratsuka S, Nakamura K, Iwai S, et al. MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer Cell 2002;2(4):289–300.

    Article  PubMed  CAS  Google Scholar 

  42. Hattori K, Heissig B, Wu Y, et al. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med 2002;8(8):841–9.

    PubMed  CAS  Google Scholar 

  43. Quinn TP, Peters KG, De Vries C, Ferrara N, Williams LT. Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc Natl Acad Sci USA 1993;90(16):7533–7.

    Article  PubMed  CAS  Google Scholar 

  44. Shalaby F, Rossant J, Yamaguchi TP, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 1995;376(6535):62–6.

    Article  PubMed  CAS  Google Scholar 

  45. Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling – in control of vascular function. Nat Rev Mol Cell Biol 2006;7(5):359–71.

    Article  PubMed  CAS  Google Scholar 

  46. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 1998;92(6):735–45.

    Article  PubMed  CAS  Google Scholar 

  47. Okada F, Rak JW, Croix BS, et al. Impact of oncogenes in tumor angiogenesis: mutant K-ras up-regulation of vascular endothelial growth factor/vascular permeability factor is necessary, but not sufficient for tumorigenicity of human colorectal carcinoma cells. Proc Natl Acad Sci USA 1998;95(7):3609–14.

    Article  PubMed  CAS  Google Scholar 

  48. Lonser RR, Glenn GM, Walther M, et al. von Hippel-Lindau disease. Lancet 2003;361(9374):2059–67.

    Article  PubMed  CAS  Google Scholar 

  49. Kim KJ, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo. Nature 1993;362:841–4.

    Article  PubMed  CAS  Google Scholar 

  50. Manley PW, Martiny-Baron G, Schlaeppi JM, Wood JM. Therapies directed at vascular endothelial growth factor. Expert Opin Investig Drugs 2002;11(12):1715–36.

    Article  PubMed  CAS  Google Scholar 

  51. Prewett M, Huber J, Li Y, et al. Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis. Cancer Res 1999;59:5209–18.

    PubMed  CAS  Google Scholar 

  52. Gerber HP, Kowalski J, Sherman D, Eberhard DA, Ferrara N. Complete inhibition of rhabdomyosarcoma xenograft growth and neovascularization requires blockade of both tumor and host vascular endothelial growth factor. Cancer Res 2000;60:6253–8.

    PubMed  CAS  Google Scholar 

  53. Holash J, Davis S, Papadopoulos N, et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA 2002;99(17):11393–8.

    Article  PubMed  CAS  Google Scholar 

  54. Dong J, Grunstein J, Tejada M, et al. VEGF-null cells require PDGFR alpha signaling-mediated stromal fibroblast recruitment for tumorigenesis. EMBO J 2004;23:2800–10.

    Article  PubMed  CAS  Google Scholar 

  55. Tejada M, Yu L, Dong J, et al. Tumor-driven paracrine PDGF receptor – a signaling is a key determinent of stromal cell recruitment in a model of human lung carcinoma. Clin Cancer Res 2006;12:2676–88.

    Article  PubMed  CAS  Google Scholar 

  56. Klement G, Baruchel S, Rak J, et al. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity [see comments]. J Clin Invest 2000;105(8):R15–24.

    Article  PubMed  CAS  Google Scholar 

  57. Lee CG, Heijn M, di Tomaso E, et al. Anti-vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions. Cancer Res 2000;60:5565–70.

    PubMed  CAS  Google Scholar 

  58. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005;307(5706):58–62.

    Article  PubMed  CAS  Google Scholar 

  59. Presta LG, Chen H, O’Connor SJ, et al. Humanization of an anti-VEGF monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997;57:4593–9.

    PubMed  CAS  Google Scholar 

  60. Ferrara N, Hillan KJ, Gerber HP, Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 2004;3(5):391–400.

    Article  PubMed  CAS  Google Scholar 

  61. Gasparini G, Longo R, Toi M, Ferrara N. Angiogenic inhibitors: a new therapeutic strategy in oncology. Nat Clin Pract Oncol 2005;2(11):562–77.

    Article  PubMed  CAS  Google Scholar 

  62. Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature 2005;438:967–74.

    Article  PubMed  CAS  Google Scholar 

  63. Jain RK, Duda DG, Clark JW, Loeffler JS. Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol 2006;3(1):24–40.

    Article  PubMed  CAS  Google Scholar 

  64. 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.

    Article  PubMed  CAS  Google Scholar 

  65. 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.

    Article  PubMed  CAS  Google Scholar 

  66. Johnson DH, Fehrenbacher L, Novotny WF, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 2004;22(11):2184–91.

    Article  PubMed  CAS  Google Scholar 

  67. 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(12):1539–44.

    Article  PubMed  CAS  Google Scholar 

  68. Rini B, Rixe O, Bukowski R, et al. AG-013736, a multi-target tyrosine kinase receptor inhibitor, demonstrates anti-tumor activity in a Phase 2 study of cytokine-refractory, metastatic renal cell cancer (RCC). ASCO Annual Meeting Proceedings 2005;Abstract 4509.

    Google Scholar 

  69. Smith JK, Mamoon NM, Duhe RJ. Emerging roles of targeted small molecule protein-tyrosine kinase inhibitors in cancer therapy. Oncol Res 2004;14(4–5):175–225.

    PubMed  Google Scholar 

  70. Maki RG, Fletcher JA, Heinrich MC, et al. Results from a continuation trial of SU11248 in patients (pts) with imatinib (IM)-resistant gastrointestinal stromal tumor (GIST). ASCO Annual Meeting Proceedings 2005;Abstract 9011.

    Google Scholar 

  71. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356(2):115–24.

    Article  PubMed  CAS  Google Scholar 

  72. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007;356(2):125–34.

    Article  PubMed  CAS  Google Scholar 

  73. Miller JW, Adamis AP, Shima DT, et al. Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am J Pathol 1994;145(3):574–84.

    PubMed  CAS  Google Scholar 

  74. Safran M, Kaelin WJ, Jr. HIF hydroxylation and the mammalian oxygen-sensing pathway. J Clin Invest 2003;111:779–83.

    PubMed  CAS  Google Scholar 

  75. Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. [see comments]. N Engl J Med 1994;331(22):1480–7.

    Article  PubMed  CAS  Google Scholar 

  76. Malecaze F, Clemens S, Simorer-Pinotel V, et al. Detection of vascular endothelial growth factor mRNA and vascular endothelial growth factor-like activity in proliferative diabetic retinopathy. Arch Ophthalmol 1994;112:1476–82.

    Article  PubMed  CAS  Google Scholar 

  77. Aiello LP, Pierce EA, Foley ED, et al. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci USA 1995;92(23):10457–61.

    Article  PubMed  CAS  Google Scholar 

  78. Adamis AP, Shima DT, Tolentino MJ, et al. Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate. Arch Ophthalmol 1996;114(1):66–71.

    Article  PubMed  CAS  Google Scholar 

  79. Ozaki H, Seo MS, Ozaki K, et al. Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization. Am J Pathol 2000;156(2):697–707.

    Article  PubMed  CAS  Google Scholar 

  80. Congdon N, O'Colmain B, Klaver CC, et al. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol 2004;122(4):477–85.

    Article  PubMed  Google Scholar 

  81. Ferris FL, III, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol 1984;102(11):1640–2.

    Article  PubMed  Google Scholar 

  82. Photodynamic Therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin. One-year results of 2 Randomized Clinical Trials—TAP Report 1. Arch Ophthalmol 1999; 117:1329–45.

    Google Scholar 

  83. Gragoudas ES, Adamis AP, Cunningham ET, Jr, Feinsod M, Guyer DR. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 2004;351(27):2805–16.

    Article  PubMed  CAS  Google Scholar 

  84. Ferrara N, Damico L, Shams N, Lowman H, Kim R. Developmemt of Ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina 2006;26:859–70.

    Article  PubMed  Google Scholar 

  85. Ng EW, Sima DT, Calias P, Cunningham ET, Jr, Guyer DR, Adamis AP. Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat Rev Drug Discov 2006;5:123–32.

    Article  PubMed  CAS  Google Scholar 

  86. Chen Y, Wiesmann C, Fuh G, et al. Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen. J Mol Biol 1999;293(4):865–81.

    Article  PubMed  CAS  Google Scholar 

  87. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355:1419–31.

    Article  PubMed  CAS  Google Scholar 

  88. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355(14):1432–44.

    Article  PubMed  CAS  Google Scholar 

  89. Casanovas O, Hicklin DJ, Bergers G, Hanahan D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 2005;8(4):299–309.

    Article  PubMed  CAS  Google Scholar 

  90. Kerbel RS, Yu J, Tran J, et al. Possible mechanisms of acquired resistance to anti-angiogenic drugs: implications for the use of combination therapy approaches. Cancer Metastasis Rev 2001;20(1–2):79–86.

    Article  PubMed  CAS  Google Scholar 

  91. Shojaei F, Wu X, Malik AK, et al. Tumor refrectoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol 2007;8:911–20.

    Article  Google Scholar 

  92. Gerber HP, Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res 2005;65(3):671–80.

    PubMed  CAS  Google Scholar 

  93. Jubb AM, Hurwitz HI, Bai W, et al. Impact of vascular endothelial growth factor-A expression, thrombospondin-2 expression, and microvessel density on the treatment effect of bevacizumab in metastatic colorectal cancer. J Clin Oncol 2006;24:217–27.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Genentech, South San Francisco, CA, USA

    Napoleone Ferrara MD

Authors
  1. Napoleone Ferrara MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Surgical Oncology, University of California, San Francisco, Divisadero St. 1600, San Francisco, 94115, USA

    Stanley P. L. Leong

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Humana Press, a part of Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Ferrara, N. (2009). Vascular Endothelial Growth Factor: Basic Biology and Clinical Applications. In: Leong, S. (eds) From Local Invasion to Metastatic Cancer. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-087-8_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-60327-087-8_2

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60327-086-1

  • Online ISBN: 978-1-60327-087-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation