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Colorectal Cancer pp 739–757Cite as

Angiogenesis and Colorectal Cancer

From the Laboratory to the Clinic

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

Abstract

When in 1998 a New York Times front-page article declared that a new class of drugs could potentially cure cancers by cutting off their blood supply, the eyes of the world turned to the field of angiogenesis (1). Actually, it had been in 1966 when Folkman and his colleagues first observed that in order to grow beyond a size of 1–2 mm3, tumors depended on new blood vessel growth, a process termed angiogenesis. Over 30 yr later, and after the expansion of this work in several laboratories around the world, more is known about angiogenesis and tumor biology and several drugs have been developed that interfere with various parts of this process. Although much of the success in 1998 was limited to preclinical models and the occasional anecdotal patient, currently large-scale human clinical trials are underway, some with quite promising results. Whatever we learn from this ongoing set of studies will undoubtedly help us understand the process by which new vessels are created, what mechanisms of resistance to therapy exist, if any, and whether existing anticancer therapy will work synergistically or in competition with these new agents. We will hopefully learn whether angiogenesis is a central part of all tumor growth or whether it might be restricted to certain disease types and stages. Above all, we will gain in our understanding of clinical trial design, as these agents have very different characteristics from conventional cytotoxic chemotherapy. This chapter attempts to summarize the current knowledge base with regards to these very challenging questions.

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References

  1. Kolata G. HOPE IN THE LAB: A special report; a cautious awe greets drugs that eradicate tumors in mice, New York Times, May 3, 1998.

    Google Scholar 

  2. Shweiki D, Itin A, Soffer D, et al. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature, 359 (1992) 843–845.

    Article  PubMed  CAS  Google Scholar 

  3. Veikkola T, Karkkainen M, Claesson-Welsh L, and Alitalo K. Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer Res., 60 (2000) 203–212.

    PubMed  CAS  Google Scholar 

  4. Asahara T, Murohara T, Sullivan A., et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science, 275 (1997) 964–967.

    Article  PubMed  CAS  Google Scholar 

  5. Waltenberger J, Claesson-Welsh L, Siegbahn A, Shibuya M, and Heldin C.-H. Different signal transduction properties of KDR and Flt-1, two receptors for vascular endothelial growth factor. J. Biol. Chem.,269 (1994) 26,988–26,995.

    Google Scholar 

  6. Landgren E, Schiller P, Cao Y, and Claesson-Welsh L. Placenta growth factor stimulates MAP kinase and mitogenicity but not phospholipase C-g and migration of endothelial cells expressing Flt-1. Oncogene, 16 (1998) 359–367.

    Article  PubMed  CAS  Google Scholar 

  7. D’Angelo G, Struman I, Martial J, and Winer RI. Activation of mitogen-activated proteinase kinases by vascular endothelial growth factor and basic fibroblast growth factor in capillary endothelial cells is inhibited by the antiangiogenic factor 16-kDa N-terminal fragment of prolactin. Proc. Natl. Acad. Sci. USA, 92 (1995) 6374–6378.

    Article  PubMed  Google Scholar 

  8. Nor JE, Christensen J, Mooney DJ, and Polverini PJ. Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bc1–2 expression. Am. J. Pathol., 154 (1999) 375–384.

    Article  PubMed  CAS  Google Scholar 

  9. O’Conner DS, Schechner JS, Adida C, et al. Control of apotosis during angiogenesis by surviving expression in endothelial cells. Am. J. Pathol., 156 (2000) 393–398.

    Article  Google Scholar 

  10. Kim I, Kim HG, So J-N, Kim JH, Kwak HJ, and Koh GY. Angiopoietin-1 regulates endothelial cell survival through the phosphatidylinositol 3’-kinase/Akt signal transduction pathway. Circ. Res., 86 (2000) 24–29.

    Article  PubMed  CAS  Google Scholar 

  11. Paku S and Paweletz N. First steps of tumor-related angiogenesis. Lab. Invest., 65 (1991) 334–346.

    PubMed  CAS  Google Scholar 

  12. Pattersson A, Nagy JA, Brown LF, et al. Heterogeneity of the angiogenic response induced in different normal adult tissues by vascular permeability factor/vascular endothelial growth factor. Lab. Invest., 80 (2000) 99–115.

    Article  Google Scholar 

  13. Djonov V, Schmid M, Tschanz SA, and Burri PH. Intussusceptive angiogenesis: its role in embryonic vascular network formation. Circ. Res., 86 (2000) 286–292.

    Article  PubMed  CAS  Google Scholar 

  14. Patan S, Munn LL, and Jain RK. Intussusceptive microvascular growth in a human colon adenocarcinoma xenograft: a novel mechanism of tumor angiogenesis. Microvasc. Res., 51 (1996) 260–272.

    Article  PubMed  CAS  Google Scholar 

  15. Metzger RJ and Krasnow MA. Genetic control of branching morphogenesis. Science, 284 (1999) 1635–1639.

    Article  PubMed  CAS  Google Scholar 

  16. Ausprunk D and Folkman J Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc. Res., 14 (1977) 43–65.

    Article  Google Scholar 

  17. Pepper MS, Ferrara N, Orci L, and Montesano R. Vascular endothelial growth factor (VEGF) induces plasminogen activators and plasminogen activator inhibitor-1 in microvascular endothelial cells. Biochem. Biophys. Res. Commun., 181 (1991) 902–906.

    Article  PubMed  CAS  Google Scholar 

  18. Zetter BR. Migration of capillary endothelial cells is stimulated by tumor-derived factors. Nature, 285 (1980) 41–43.

    Article  PubMed  CAS  Google Scholar 

  19. Asahara T, Chem D, Takahashi T, et al. Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulated VEGF-induced postnatal neovascularization. Circ. Res., 83 (1998) 233–240.

    Article  PubMed  CAS  Google Scholar 

  20. Maisonpierre PC, Suri C, Jones PF, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science, 277 (1997) 55–60.

    Article  PubMed  CAS  Google Scholar 

  21. Friedlander M, Brooks PC, Shaffer RW, Kincaid CM, Varner JA, and Cheresh DA. Definition of two angiogenic pathways by distinct alpha v integrins. Science, 270 (1995) 1500–1502.

    Article  PubMed  CAS  Google Scholar 

  22. Brooks PC, Montgomery AM, Rosenfeld M, et al. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell, 79 (1994) 1157–1164.

    Article  PubMed  CAS  Google Scholar 

  23. Nelson AR, Fingleton B, Rothenberg ML, and Martrisian LM. Matrix metalloproteinases: biologic activity and clinical implications. J. Clin. Oncol., 18 (2000) 1135–1149.

    PubMed  CAS  Google Scholar 

  24. Sang QXA. Complex role of matrix metalloproteinases in angiogenesis. Cell Res., 8 (1998) 171–177.

    Article  PubMed  CAS  Google Scholar 

  25. Nangio-Makker P, Honjo Y, Sarvis R, et al. Galectin-3 induces endothelial cell morphogenesis and angiogenesis. Am. J. Pathol., 156 (2000) 899–909.

    Article  Google Scholar 

  26. Gamble J, Meyer G, Noack L, et al. B1 integrin activation inhibits in vitro tube formation: effects of cell migration, vacuole coalescence and lumen formation. Endothelium, 7 (1999) 23–34.

    PubMed  CAS  Google Scholar 

  27. Yang S, Graham J, Kahn J, Schwartz EA, and Gerritsen ME. Functional roles for PECAM-1 (CD31) and VE-cadherin (CD144) in tube assembly and lumen formation in three-dimensional collagen gels. Am. J. Pathol., 155 (1999) 887–895.

    Article  PubMed  CAS  Google Scholar 

  28. Meyer GT, Matthias LJ, Noack L, Vadas MA, and Gamble JR. Lumen formation during angiogenesis in vitro involves phagocytic activity, formation and secretion of vacuoles, cell death, and capillary tube remodeling by different populations of endothelial cells. Anat. Rec., 249 (1997) 327–340.

    Article  PubMed  CAS  Google Scholar 

  29. Maniotis AJ, Folberg R, Hess A, et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am. J. Pathol., 155 (1999) 739–752.

    Article  PubMed  CAS  Google Scholar 

  30. McDonald DM, Munn L, and Jain RK. Vasculogenic mimicry: how convincing, how novel and how significant ? Am. J. Pathol., 156 (2000) 383–388.

    Article  PubMed  CAS  Google Scholar 

  31. Wang HU, Chen ZF, and Anderson DJ. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell, 93 (1998) 741–753.

    Article  PubMed  CAS  Google Scholar 

  32. Adams RH, Wilkinson GA, Weiss C, et al. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dey., 13 (1999) 295–306.

    Article  CAS  Google Scholar 

  33. Yancopoulos GD, Klagsbrun M, and Folkman J Vasculogenesis, angiogenesis and growth factors: ephrins enter the fray at the border. Cell, 93 (1998) 661–664.

    CAS  Google Scholar 

  34. Mellitzer G, Xu Q, and Wilkinson DG. Eph receptors and ephrins restrict cell intermingling and communication. Nature, 400 (1999) 77–81.

    Article  PubMed  CAS  Google Scholar 

  35. Adams RH, Wilkinson GA, Weiss C, et al. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dey., 13 (1999) 295–306.

    Article  CAS  Google Scholar 

  36. Folkman J and D’Amore PA. Blood formation: what is its molecular basis? Cell, 87 (1996) 1153–1155.

    Article  PubMed  CAS  Google Scholar 

  37. Darland DC and D’Amore PA. Blood vessel maturation: vascular development comes of age. J. Clin. Invest., 103 (1999) 157–158.

    Article  PubMed  CAS  Google Scholar 

  38. Hayes AJ, Huang WQ, Mallah J, Yang D, Lippman ME, and Li LY. Angiopoietin-1 and its receptor Tie-2 participate in the regulation of capillary-like tubule formation and survival of endothelial cells. Microvasc. Res., 58 (1999) 224–237.

    Article  PubMed  CAS  Google Scholar 

  39. Antonelli-Orlidge A, Saunders KB, Smith SR, and D’Amore PA. An activated form of transforming growth factor beta is produced by cocultures of endothelial cells and pericytes. Proc. Natl. Acad. Sci. USA, 86 (1989) 4544–4548.

    Article  PubMed  CAS  Google Scholar 

  40. Maisonpierre PC, Suri C, Jones PF, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science, 277 (1997) 55–60.

    Article  PubMed  CAS  Google Scholar 

  41. Engel CJ, Bennett ST, Chambers AF, Doig GS, Kerkvliet N, and O’Malley FP. Tumor angiogenesis predicts recurrence in invasive colorectal cancer when controlled for Dukes staging. Am. J. Surg. Pathol., 20 (1996) 1260–1265.

    Article  PubMed  CAS  Google Scholar 

  42. Saclarides TJ. Angiogenesis in colorectal cancer. In New and Controverial Issues in the Management of Colorectal Diseases. 1997, vol. 77, pp. 253–260.

    CAS  Google Scholar 

  43. Pietra N, Sarli L, Caruana P, Cabras A, Costi R, Gobbi S, et al. Is tumour angiogenesis a prognostic factor in patients with colorectal cancer and no involved nodes? Eur. J. Surg., 166 (2000) 552–556.

    Article  PubMed  CAS  Google Scholar 

  44. Takahashi YT, Tucker SL, Kitadai Y, et al. Vessel counts and expression of vacular endothelial growth factors as prognostic factors in node-negative colon cancer. Arch. Surg., 132 (1997) 541–546.

    Article  PubMed  CAS  Google Scholar 

  45. Dirix LY, Vermeulen PB, Hubens G, et al. Serum basic fibroblast growth factor and vascular endothelial growth factor and tumour growth kinetics in advanced colorectal cancer. Ann. Oncol., 7 (1996) 843–848.

    Article  PubMed  CAS  Google Scholar 

  46. Hyodo I, Doi T, Endo H, et al. Clinical significance of plasma vascular endothelial growth factor in gastrointestinal cancer. Eur. J. Cancer, 34 (1998) 2041–2045.

    Article  PubMed  CAS  Google Scholar 

  47. Broil R, Erdmann H, Duchrow M, Oevermann E, Schwandner O, Market U, et al. Vascular endothelial growth factor (VEGF)-a valuable serum tumour marker in patients with colorectal cancer? Eur. J. Surg. Oncol., 27 (2001) 37–42.

    Article  Google Scholar 

  48. Kondo Y, Aril S, Furutani M, Isigami S-I, Mori A, Onodera H, et al. Implication of vascular endothelial growth factor and p53 status for angiogenesis in noninvasive colorectal carcinoma. Cancer, 88 (2000) 1820–1827.

    Article  PubMed  CAS  Google Scholar 

  49. Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N. Engl. J. Med., 342 (26) (2000) 1946–1952.

    Article  PubMed  CAS  Google Scholar 

  50. Gallo O, Franchi A, Magnelli L, Sardi I, Vannacci A, Boddi V, et al. Cyclooxygenase-2 pathway correlates with VEGF expression in head and neck cancer. Neoplasia, 3 (1) (2001) 53–61.

    Article  PubMed  CAS  Google Scholar 

  51. Masferrer JL, Leahy KM, Koki AT, Zweifel BS, Settle SL, Woerner BM, et al. Antiangiogenic and antitumor activities of cyclooxygenase-1 inhibitors. Cancer Res., 60 (5) (2000) 1306–1311.

    PubMed  CAS  Google Scholar 

  52. Zebrowski BK, Liu W, Ramirez K, Akagi Y, Mills GB, and Ellis LM. Markedly elevated levels of vascular endothelial growth factor in malignant ascites. Ann. Surg. Oncol., 6 (1999) 373–378.

    Article  PubMed  CAS  Google Scholar 

  53. White CW, Sondheimer HM, Crouch EC, Wilson H, and Fan LL. Treatment of pulmonary hemangiomatosis with recombinant interferon alpha-2a. N. Engl. J. Med., 320 (1989) 1197–1200.

    Article  PubMed  CAS  Google Scholar 

  54. Carter SK. Clinical strategy for the development of angiogenesis inhibitors. Oncologist, 5 (Suppl. 1) (2000) 51–54.

    Article  PubMed  CAS  Google Scholar 

  55. Thompson WD, Li WW, and Maragoudakis M. The clinical manipulation of angiogenesis: pathology, side-effects, surprises, and opportunities with novel human therapies. J. Pathol., 187 (1999) 503–510.

    Article  PubMed  CAS  Google Scholar 

  56. Li WW, Li VW, and Casey R. Clinical trials of angiogenesis-based therapies: overview and new guiding principles. In Angiogenesis: Models, Modulators, and Clinical Applications. Maragoudakis M (ed.), New York, Plenum, 1998, pp. 475–492.

    Google Scholar 

  57. Yu JL, Rak JW, Carmeliet P, Nagy A, Kerbel RS, and Coomber BL. Heterogenous vascular dependence of tumor cell populations. Am. J. Pathol., 158 (2001) 1325–1334.

    Article  PubMed  CAS  Google Scholar 

  58. Boye E, Yu Y, Paranya G, Mulliken JB, Olsen BR, and Bischoff J. Clonality and altered behavior of endothelial cells from hemangiomas.. 1. Clin. Invest., 107 (2001) 745–752.

    Article  CAS  Google Scholar 

  59. Dinney CP, Bielenberg DR, Perrotte P, et al. Inhibition of basic fibroblast growth factor expression, angiogenesis, and growth of human bladder carcinoma in mice by systemic interferon-alpha administration. Cancer Res., 58 (1998) 808–814.

    PubMed  CAS  Google Scholar 

  60. Takano S, Gately S, Neville ME, et al. Suramin, an anticancer and angiosuppressive agent, inhibits endothelial cell binding of basic fibroblast growth factor, migration, proliferation, and reduction of urokinase-type plasminogen activator. Cancer Res., 54 (1994) 2654–2660.

    PubMed  CAS  Google Scholar 

  61. Sandberg JA, Bouhana KS, Gallegos AM, et al. Pharmacokinetics of an antiangiogenic ribozyme (ANGIOZYME) in the mouse. Antisense Nucleic Acid Drug Dev., 9 (1999) 271–277.

    Article  PubMed  CAS  Google Scholar 

  62. Li CY, Shan S, Huang Q, et al. Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models. J. Natl. Cancer Inst., 92 (2000) 143–147.

    Article  PubMed  CAS  Google Scholar 

  63. Borgstrom P, Gold DP, Hillan KJ, and Ferrara N. Importance of VEGF for breast cancer angiogenesis in vivo: implications from intravital microscopy of combination treatments with an anti-VEGF neutralizing monoclonal antibody and doxorubicin. Anticancer Res., 19 (1999) 4203–4214.

    PubMed  CAS  Google Scholar 

  64. Roeckl W, Hecht D, Sztajer H, Waltenberger J, Yayon A, and Weich HA. Differential binding characteristics and cellular inhibition by soluble VEGF receptors 1 and 2. Exp. Cell Res., 241 (1998) 161–170.

    Article  PubMed  CAS  Google Scholar 

  65. Nor JE, Christensen J, Mooney DJ, and Polverini PJ. Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl-2 expression. Am. J. Pathol., 154 (1999) 375–384.

    Article  PubMed  CAS  Google Scholar 

  66. O’Conner DS, Schechner JS, Adida C, et al. Control of apotosis during angiogenesis by surviving expression in endothelial cells. Am. J. Pathol., 156 (2000) 393–398.

    Article  Google Scholar 

  67. Nelson AR, Fingleton B, Rothenberg ML, and Martrisian LM. Matrix metalloproteinases: biologic activity and clinical implications. J. Clin. Oncol., 18 (2000) 1135–1149.

    PubMed  CAS  Google Scholar 

  68. Itoh T, Tanioka M, Yoshida H, Yoshioka T, Nishimoto H, and Itohara S. Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res., 58 (1998) 1048–1051.

    PubMed  CAS  Google Scholar 

  69. Vu TH, Shipley JM, Bergers G, et al. MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell, 93 (1998) 411–422.

    Article  PubMed  CAS  Google Scholar 

  70. Gaincotti FG and Ruoslahti E. Integrin signaling. Science, 285 (1999) 1028–1032.

    Article  Google Scholar 

  71. Cheresh DA. Death to a blood vessel, death to a tumor. Nat. Med., 4 (1998) 395–396.

    Article  PubMed  CAS  Google Scholar 

  72. Ito H, Rovira II, Bloom ML, Takeda K, Ferrans VJ, Quyyumi AA, et al. Endothelial progenitor cells as putative targets for angiostatin. Cancer Res., 59 (1999) 5875–5877.

    PubMed  CAS  Google Scholar 

  73. Kim KJ, Li B, Houck K, et al. The vascular endothelial growth factor proteins: Identification of biologically relevant regions by neutralizing monoclonal antibodies. Growth Factors, 7 (1992) 53–64.

    Article  PubMed  CAS  Google Scholar 

  74. Kim K, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature, 362 (1993) 841–844.

    Article  PubMed  CAS  Google Scholar 

  75. Gordon MS, Margolin K, Talpaz M, Sledge GW Jr, Holmgren E, Benjamin R, et al. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J. Clin. Onc., 19 (2001) 843–850.

    CAS  Google Scholar 

  76. Margolin K, Gordon MS, Holmgren E, Gaudreault J, Novotny W, Fyfe G, et al. Phase Ib trial of intravenous recombinant humanized monoclonal antibody to vascular endothelial growth factor in combination with chemotherapy in patients with advanced cancer: pharmacologic and long-term safety data. J. Clin. Onc., 19 (2001) 851–856.

    CAS  Google Scholar 

  77. Bergsland E, Hurwitz H, Fehrenbacher L, Meropol NJ, Novotny WF, Gaudreault J, et al. A randomized phase II trial comparing rhuMAb VEGF (recombinant humanized monoclonal antibody to vascular endothelial cell growth factor) plus 5-fluorouracil/leucovorin (FU/LV) to FU/LV alone in patients with metastatic colorectal cancer. Am. Soc. Clin. Sci., 19:242a (2000) 939 (abstract).

    Google Scholar 

  78. Fong TAT, Shawver LK, Sun L, et al. SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res., 59 (1999) 99–106.

    PubMed  CAS  Google Scholar 

  79. Mendel DB, Laird AD, Smolich BD, et al. Development of SU5416, a selective small molecule inhibitor of VEGF receptor tyrosine kinase activity, as an angiogenesis agent. Anticancer Drug Des., 15 (2000) 29–41

    PubMed  CAS  Google Scholar 

  80. Rosen LS, Kabbinavar F, Rosen P, Mulay M, Quigley S, and Hannah AL. Phase I trial of SU5416. A novel angiogenesis inhibitor in patients with advanced malignancies. Proc. Amer. Soc. Oncol. (1998) 218a.

    Google Scholar 

  81. Levine M, Hirsh J, Gent M, et al. Double-blind randomized trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet, 343 (8902) (1994) 886–889.

    Article  PubMed  CAS  Google Scholar 

  82. Bern MM, Lokich JJ, Wallach SR, et al. Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomized prospective trial. Ann. Intern. Med., 112 (6) (1990) 423–428.

    Article  PubMed  CAS  Google Scholar 

  83. Monreal M, Alastrue A, Rull M, et al. Upper extremity deep venous thrombosis in cancer patients with venous access devices-prophylaxis with a low molecular weight heparin (Fragmin) Thromb. Haemost., 75(2) (1996) 251–253.

    PubMed  CAS  Google Scholar 

  84. Kamphaus GD, Colorado PC, Panka DJ, Hopfer H, Ramchandran R, Torre A, et al. Canstatin, a novel matrix-derived inhibitor of angiogenesis and tumor growth. J. Biol. Chem., 275 (2000) 1209–1215

    CAS  Google Scholar 

  85. Lucas R, Holmgren L, Garcia I, et al. Multiple forms of angiostatin induce apoptosis in endothelial cells. Blood, 92 (1998) 4730–4741.

    PubMed  CAS  Google Scholar 

  86. Dhanabal M, Ramchandran R, Waterman JM, et al. Endostatin induces endothelial cell apoptosis. J. Biol. Chem., 274 (1999) 11,721–11,726.

    Google Scholar 

  87. SU5416 Investigator brochure, SUGEN, Inc., South San Francisco, CA.

    Google Scholar 

  88. Rosen, P, Amado R, Hecht JR, Chang D, Mulay M, Parson M, et al. A phase I/II study of SU5416 in combination with 5-FU/leucovorin in patients with metastatic colorectal cancer. Am. Soc. Clin. Oncol., 19 (2000) 3a (abstract).

    Google Scholar 

  89. Miller LL, Elfring GL, Hannah AL, Allred R, Scigalla P, and Rosen LS. Efficacy results of a phase I/II study of SU5416 (S)/5-fluorouracil (F)/leucovorin (L) relative to results in random subsets of similar patients (Pts) from a phase III study of irinotecan (C)/F/L or F/L alone in the therapy of previously untreated metastatic colorectal cancer (MCRC). Am. Soc. Clin. Oncol., 20 (2001) 144a (abstract).

    Google Scholar 

  90. Saltz LB, Box JV, Blanke C, Rosen LS, Fehrnabacher L, Moore MJ, et al. for the Irinotecan Study Group. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. N. Eng. J. Med., 343 (2000) 905–914.

    Article  CAS  Google Scholar 

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  1. Lee S. Rosen
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  2. William W. Li
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  1. Gastrointestinal Oncology Division, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Leonard B. Saltz MD

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Rosen, L.S., Li, W.W. (2002). Angiogenesis and Colorectal Cancer. In: Saltz, L.B. (eds) Colorectal Cancer. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-160-2_39

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  • DOI: https://doi.org/10.1007/978-1-59259-160-2_39

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