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Perspectives on the Future of Angiogenesis Research

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Angiogenesis

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The future of angiogenesis research holds great promise. Future prospects can be appreciated from the perspectives of historical landmarks in the field, and of the landscape of our current understanding about the regulation of angiogenesis and manifestations of the vasculature, in particular the parameters of the angiogenic switch. Looking ahead, five milestone goals for the field are highlighted, centered upon elucidating the intracellular integrated circuits that process a multitude of regulatory signals received from the extracellular microenvironment. This global regulatory network involves signals transmitted amongst a set of cell types constituting a core of the angiogenic system: endothelial cells, pericytes, and a variety of vascular regulatory leukocytes, as well as the vascular stem and progenitor cells that spawn these component cells. The realization of these strategic goals will set the stage for translation of the new knowledge to human medicine, as elaborated in seven postulates of future applications that could have profound impact on the treatment and prevention of human diseases, in particular cancers.

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References

  1. Folkman J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 1971; 285:1182–86.

    PubMed  CAS  Google Scholar 

  2. Folkman, J. History of Angiogenesis. 2008. Chapter 1. This volume.

    Google Scholar 

  3. Folkman, J. Tumor Angiogenesis: from Bench to Bedside. In: Tumor Angiogenesis: Basic Mechanisms and Cancer Therapy. Marme, D., Fusenig, N., eds., Springer, New York, New York, 2007; in press.

    Google Scholar 

  4. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996; 86:353–64.

    Article  PubMed  CAS  Google Scholar 

  5. Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005; 438:932–36.

    Article  PubMed  CAS  Google Scholar 

  6. Adams R.H., Alitalo, K. Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol. 2007; 8:464–78.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Folkman J. Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov. 2007; 6:273–86.

    Article  PubMed  CAS  Google Scholar 

  9. Casanovas O, Hicklin DJ, Bergers G, et al. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell. 2005; 8: 299–309.

    Article  PubMed  CAS  Google Scholar 

  10. Kerbel RS. Therapeutic implications of intrinsic or induced angiogenic growth factor redundancy in tumors revealed. Cancer Cell. 2005; 8:269–71.

    Article  PubMed  CAS  Google Scholar 

  11. 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.

    Article  PubMed  CAS  Google Scholar 

  12. Shojaei F, Wu X, Malik AK, et al. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b(+) Gr1(+) myeloid cells. Nat Biotechnol.; 25:911–20.

    Google Scholar 

  13. Kamba T, McDonald DM. Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer. 2007; 96:1788–95.

    Article  PubMed  CAS  Google Scholar 

  14. Verheul HM, Pinedo HM. Possible molecular mechanisms involved in the toxicity of angiogenesis inhibition. Nat Rev Cancer. 2007; 7:475–85.

    Article  PubMed  CAS  Google Scholar 

  15. Bergers G, Song S. The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol. 2005; 7:452–64.

    Article  PubMed  CAS  Google Scholar 

  16. von Tell D, Armulik A, Betsholtz C. Pericytes and vascular stability. Exp Cell Res. 2006; 312:623–29.

    Article  Google Scholar 

  17. Bergers, G. Pericytes, the Mural Cells of the Microvascular Stystem. 2008. Chapter 4; this volume.

    Google Scholar 

  18. Bergers G, Song S, Meyer-Morse N, et al. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest. 2003; 111:1287–95.

    PubMed  CAS  Google Scholar 

  19. R. Erber, A. Thurnher, A.D. Katsen, et al. Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms, FASEB J. 2004; 18: 338–40.

    PubMed  CAS  Google Scholar 

  20. Pietras K, Hanahan D. A multitargeted, metronomic, and maximum-tolerated dose “chemo-switch” regimen is antiangiogenic, producing objective responses and survival benefit in a mouse model of cancer. J Clin Oncol. 2005; 23:939–52.

    Article  PubMed  CAS  Google Scholar 

  21. Sennino B, Falcon BL, McCauley D, et al. Sequential loss of tumor vessel pericytes and endothelial cells after inhibition of platelet-derived growth factor B by selective aptamer AX102. Cancer Res. 2007; 67:7358–67.

    Article  PubMed  CAS  Google Scholar 

  22. Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003; 3:401–10.

    Article  PubMed  CAS  Google Scholar 

  23. Detmar, M. Lymphatic vascular system and Lymphangiogenesis. 2007. Chapter 43, this volume.

    Google Scholar 

  24. Shibuya M, Claesson-Welsh L. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp Cell Res. 2006; 312:549–60.

    Article  PubMed  CAS  Google Scholar 

  25. Shibuya, M. Vascular Permeabiliy Factor/Vascular Endothelial Growth Factor. 2008. Chapter 8, this volume.

    Google Scholar 

  26. Klagsbrun M, Eichmann A. A role for axon guidance receptors and ligands in blood vessel development and tumor angiogenesis. Cytokine Growth Factor Rev. 2005; 16:535–48.

    Article  PubMed  CAS  Google Scholar 

  27. Claesson-Welsh. VEGF Signal Transduction in Angiogenesis. 2007. Chapter 18, this volume.

    Google Scholar 

  28. Presta, M. Fibroblast Growth Factor-2. 2007. Chapter 8, this Volume.

    Google Scholar 

  29. Thurston G. et al. Delta-like Ligand 4/Notch Pathway in Tumor Angiogenesis. 2008. Chapter 19, this volume.

    Google Scholar 

  30. 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.

    Article  PubMed  CAS  Google Scholar 

  31. Stupack DG, Cheresh DA. Integrins and angiogenesis. Curr Top Dev Biol. 2004; 64:207–38.

    Article  PubMed  CAS  Google Scholar 

  32. Kalluri R. Basement membranes: structure, assembly and role in tumour angiogenesis. Nat Rev Cancer. 2003; 3:422–33.

    Article  PubMed  CAS  Google Scholar 

  33. Davis GE, Senger DR. Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ Res. 2005; 97:1093–107.

    Article  PubMed  CAS  Google Scholar 

  34. Cheresh, D and Alavi, A. Integrins in Angiogenesis. 2008. Chapter 6, this volume.

    Google Scholar 

  35. Nyberg P, Xie L, Kalluri R. Endogenous inhibitors of angiogenesis. Cancer Res. 2005; 65:3967–79.

    Article  PubMed  CAS  Google Scholar 

  36. Ribatti D, Conconi MT, Nussdorfer GG. Nonclassic endogenous regulators of angiogenesis. Pharmacol Rev. 2007; 59:185–205.

    Article  PubMed  CAS  Google Scholar 

  37. Bornstein, P. Thrombospondins. 2008; Chapter 13, this volume.

    Google Scholar 

  38. Folkman, J. Endostatin and Angiostatin. 2008; Chapter 12, this volume.

    Google Scholar 

  39. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420:860–67.

    Article  PubMed  CAS  Google Scholar 

  40. Joyce JA, Freeman C, Meyer-Morse N, et al. A functional heparan sulfate mimetic implicates both heparanase and heparansulfate in tumor angiogenesis and invasion in a mouse model of multistage cancer. Oncogene. 2005;24:4037–51; Erratum in: Oncogene. 2005; 24:4163.

    PubMed  CAS  Google Scholar 

  41. Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res. 2006; 66:605–12.

    Article  PubMed  CAS  Google Scholar 

  42. 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; 103:12493–98.

    Article  PubMed  CAS  Google Scholar 

  43. van Kempen LC, de Visser KE, Coussens LM. Inflammation, proteases and cancer. Eur J Cancer. 2006;42:728–34.

    Article  PubMed  Google Scholar 

  44. Schmid MC, Varner JA. Myeloid cell trafficking and tumor angiogenesis. Cancer Lett. 2007;250:1–8.

    Article  PubMed  CAS  Google Scholar 

  45. Tan TT, Coussens LM. Humoral immunity, inflammation and cancer. Curr Opin Immunol. 2007; 19:209–16.

    Article  PubMed  CAS  Google Scholar 

  46. Kopp HG, Rafii S. Thrombopoietic cells and the bone marrow vascular niche. Ann N Y Acad Sci. 2007; 1106:175–9.

    Article  PubMed  CAS  Google Scholar 

  47. Coussens, LM. Immune cells and inflammatory mediators as regulators of angiogenesis. 2008; Chapter 20, this volume.

    Google Scholar 

  48. Ruoslahti E. Specialization of tumour vasculature. Nat Rev Cancer. 2002; 2:83–90.

    Article  PubMed  Google Scholar 

  49. Pasqualini R, Arap W, McDonald DM. Probing the structural and molecular diversity of tumor vasculature.Trends Mol Med. 2002; 8:563–71.

    Article  PubMed  CAS  Google Scholar 

  50. Baluk P, Hashizume H, McDonald DM. Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev. 2005; 15:102–11.

    Article  PubMed  CAS  Google Scholar 

  51. McDonald, DM. Angiogenesis and Vascular Remodeling: Biology and Architecture of the Vasculature. 2008. Chapter 2, this volume.

    Google Scholar 

  52. St Croix, B. Tumor endothelial markers. 2008. Chapter 29, this volume.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  54. Hormigo A, Gutin PH, Rafii S. Tracking normalization of brain tumor vasculature by magnetic imaging and proangiogenic biomarkers. Cancer Cell. 2007; 11:6–8.

    Article  PubMed  CAS  Google Scholar 

  55. Jain, RK. Normalization of Tumor Vasculature and Microenvironment. 2008. Chapter 24, this volume.

    Google Scholar 

  56. Rafii, S. Contributions of endothelial progenitor cells to the angiogenic process. 2008. Chapter 21, this volume.

    Google Scholar 

  57. Song S, Ewald AJ, Stallcup W, et al. PDGFRbeta+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat Cell Biol. 2005; 7:870–79.

    Article  PubMed  CAS  Google Scholar 

  58. Folkman J, Kalluri R. Cancer without disease. Nature. 2004; 427:787.

    Article  PubMed  CAS  Google Scholar 

  59. Naumov GN, Akslen LA, Folkman J. Role of angiogenesis in human tumor dormancy: animal models of the angiogenic switch. Cell Cycle. 2006; 5:1779–87.

    PubMed  CAS  Google Scholar 

  60. Soucek, L, Lawlor, ER, Soto, D, et al. Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nature Med. 2007; in press.

    Google Scholar 

  61. Lee S, Chen TT, Barber CL, et al. Autocrine VEGF Signaling Is Required for Vascular Homeostasis. Cell. 2007; 130:691–703.

    Article  PubMed  CAS  Google Scholar 

  62. Semenza GL. Therapeutic angiogenesis: another passing phase? Circ Res. 2006; 98:1115–16.

    Article  PubMed  CAS  Google Scholar 

  63. Zorick TS, Mustacchi Z, Bando SY, et al. High serum endostatin levels in Down syndrome: implications for improved treatment and prevention of solid tumours. Eur J Hum Genet. 2001; 9:811–14.

    Article  PubMed  CAS  Google Scholar 

  64. 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; 102:2934–39.

    Article  PubMed  CAS  Google Scholar 

  65. Rogers MS, D’Amato RJ. The effect of genetic diversity on angiogenesis. Exp Cell Res. 2006; 312:561–74.

    Article  PubMed  CAS  Google Scholar 

  66. Kong SY, Park JW, Lee JA, Park JE, Park KW, Hong EK, Kim CM. Association between vascular endothelial growth factor gene polymorphisms and survival in hepatocellular carcinoma patients. Hepatology. 2007; 46:446–55.

    Article  PubMed  CAS  Google Scholar 

  67. Schneider BP, Radovich M, Sledge GW, Robarge JD, Li L, Storniolo AM, Lemler S, Nguyen AT, Hancock BA, Stout M, Skaar T, Flockhart DA. Association of polymorphisms of angiogenesis genes with breast cancer. Breast Cancer Res Treat. 2007; Sep 20; [Epub ahead of print].

    Google Scholar 

  68. Heist RS, Zhai R, Liu G, Zhou W, Lin X, Su L, Asomaning K, Lynch TJ, Wain JC, Christiani DC. VEGF polymorphisms and survival in early-stage non-small-cell lung cancer. J Clin Oncol. 2008; 26:856–62.

    Article  PubMed  CAS  Google Scholar 

  69. Kim DH, Lee NY, Lee MH, Sohn SK, Do YR, Park JY. Vascular endothelial growth factor (VEGF) gene (VEGFA) polymorphism can predict the prognosis in acute myeloid leukaemia patients. Br J Haematol. 2008;140:71–9.

    Article  PubMed  CAS  Google Scholar 

  70. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000; 100:57–70.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, Helen Diller Family Comprehensive Cancer Center, 94143, San Francisco, CA, USA

    Douglas Hanahan

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  1. Douglas Hanahan
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Editors and Affiliations

  1. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    William D. Figg

  2. Department of Surgery Harvard Medical School and Vascular Biology Program, Children's Hospital Boston, Boston, MA, USA

    Judah Folkman

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Hanahan, D. (2008). Perspectives on the Future of Angiogenesis Research. In: Figg, W.D., Folkman, J. (eds) Angiogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-71518-6_48

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  • DOI: https://doi.org/10.1007/978-0-387-71518-6_48

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