Seminars in Oncology
Volume 32, Issue 1 , Pages 61-68 , February 2005

Targeting vascular endothelial growth factor and angiogenesis for the treatment of colorectal cancer

  • Timothy S. Collins

      Affiliations

    • Department of Medical Oncology, Duke University Medical Center, Durham, NC.
    • ,
  • Herbert I. Hurwitz

      Affiliations

    • Department of Medical Oncology, Duke University Medical Center, Durham, NC.
    • Corresponding Author InformationAddress reprint requests to Herbert I. Hurtwitz, MD, Duke University Medical Center, Department of Medical Oncology, Durham, NC 27710.

References 

  1. American Cancer Society . Cancer Facts and Figures . Atlanta, GA: American Cancer Society; 2004;
  2. Kuebler JP , de Gramont A . Recent experience with oxaliplatin or irinotecan combined with 5-fluorouracil and leucovorin in the treatment of colorectal cancer . Semin Oncol . 2003;30:40–46
  3. Saltz LB , Cox JV , Blanke C , et al.  Irinotecan Study Group   Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer . N Engl J Med . 2000;343:905–914
  4. Douillard JY , Cunningham D , Roth AD , et al.   Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer (A multicentre randomised trial) . Lancet . 2000;355:1041–1047
  5. Folkman J . Tumor angiogenesis (Therapeutic implications) . N Engl J Med . 1971;285:1182–1186
  6. Plouet J , Schilling J , Gospodarowicz D . Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells . EMBO J . 1989;8:3801–3806
  7. Keck PJ , Hauser SD , Krivi G , et al.   Vascular permeability factor, an endothelial cell mitogen related to PDGF . Science . 1989;246:1309–1312
  8. Connolly DT , Heuvelman DM , Nelson R , et al.   Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis . J Clin Invest . 1989;84:1470–1478
  9. Leung DW , Cachianes G , Kuang WJ , et al.   Vascular endothelial growth factor is a secreted angiogenic mitogen . Science . 1989;246:1306–1309
  10. Conn G , Bayne ML , Soderman DD , et al.   Amino acid and cDNA sequences of a vascular endothelial cell mitogen that is homologous to platelet-derived growth factor . Proc Natl Acad Sci U S A . 1990;87:2628–2632
  11. Folkman J . What is the evidence that tumors are angiogenesis dependent? . J Natl Cancer Inst . 1990;82:4–6
  12. Moehler TM , Ho AD , Goldschmidt H , et al.   Angiogenesis in hematologic malignancies . Crit Rev Oncol Hematol . 2003;45:227–244
  13. Ferrara N , Gerber HP , LeCouter J . The biology of VEGF and its receptors . Nat Med . 2003;9:669–676
  14. Bhargava P , Marshall JL , Rizvi N , et al.   A phase I and pharmacokinetic study of TNP-470 administered weekly to patients with advanced cancer . Clin Cancer Res . 1999;5:1989–1995
  15. Raymond E , Faivre S , Vera K , et al.   Final results of a phase I and pharmacokinetic study of SU11248, a novel multi-target tyrosine kinase inhibitor, in patients with advanced cancers . Proc Am Soc Clin Oncol . 2003;22:192; (abstr 769)
  16. Eskens FA . Angiogenesis inhibitors in clinical development; where are we now and where are we going? . Br J Cancer . 2004;90:1–7
  17. Wechalekar AD , Chen CI , Sutton D , et al.   Intermediate dose thalidomide (200 mg daily) has comparable efficacy and less toxicity than higher doses in relapsed multiple myeloma . Leuk Lymphoma . 2003;44:1147–1149
  18. Takebayashi Y , Aklyama S , Yamada K , et al.   Angiogenesis as an unfavorable prognostic factor in human colorectal carcinoma . Cancer 1996 . 1996;78:226–231
  19. Takahashi Y , Kitadai Y , Bucana CD , et al.   Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer . Cancer Res . 1995;55:3964–3968
  20. Takahashi Y , Tucker SL , Kitadai Y , et al.   Vessel counts and expression of vascular endothelial growth factor as prognostic factors in node-negative colon cancer . Arch Surg . 1997;132:541–546
  21. Hurwitz H , Fehrenbacher L , Cartwright T , et al.   Bevacizumab (a monoclonal antibody to vascular endothelial growth factor) prolongs survival in first-line colorectal cancer (CRC) (Results of a phase III trial of bevacizumab in combination with bolus IFL (irinotecan, 5-fluorouracil, leucovorin) as first-line therapy in subjects with metastatic CRC) . Proc Am Soc Clin Oncol . 2003; (abstr 3646)
  22. Folkman J . Role of angiogenesis in tumor growth and metastasis . Semin Oncol . 2002;29:15–18
  23. Hanahan D , Folkman J . Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis . Cell . 1996;86:353–364
  24. Cross MJ , Dixelius J , Matsumoto T , et al.   VEGF-receptor signal transduction . Trends Biochem Sci . 2003;28:488–494
  25. Olofsson B , Pajusola K , Kaipainen A , et al.   Vascular endothelial growth factor B, a novel growth factor for endothelial cells . Proc Natl Acad Sci U S A . 1996;93:2576–2581
  26. Joukov V , Pajusola K , Kaipainen A , et al.   A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases . EMBO J . 1996;15:290–298
  27. Yamada Y , Nezu J , Shimane M , et al.   Molecular cloning of a novel vascular endothelial growth factor, VEGF-D . Genomics . 1997;42:483–488
  28. Maglione D , Guerriero V , Viglietto G , et al.   Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor . Proc Natl Acad Sci U S A . 1991;88:9267–9271
  29. Ogawa S , Oku A , Sawano A , et al.   A novel type of vascular endothelial growth factor, VEGF-E (NZ-7 VEGF), preferentially utilizes KDR/Flk-1 receptor and carries a potent mitotic activity without heparin-binding domain . J Biol Chem . 1998;273:31273–31282
  30. Park JE , Keller GA , Ferrara N . The vascular endothelial growth factor (VEGF) isoforms (Differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF) . Mol Biol Cell . 1993;4:1317–1326
  31. Shweiki D , Itin A , Soffer D , et al.   Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis . Nature . 1992;359:843–845
  32. Goldman CK , Kim J , Wong WL , et al.   Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells (A model of glioblastoma multiforme pathophysiology) . Mol Biol Cell . 1993;4:121–133
  33. Pertovaara L , Kaipainen A , Mustonen T , et al.   Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells . J Biol Chem . 1994;269:6271–6274
  34. Gille J , Swerlick RA , Caughman SW . Transforming growth factor-alpha-induced transcriptional activation of the vascular permeability factor (VPF/VEGF) gene requires AP-2-dependent DNA binding and transactivation . EMBO J . 1997;16:750–759
  35. Brogi E , Wu T , Namiki A , et al.   Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth muscle cells, whereas hypoxia upregulates VEGF expression only . Circulation . 1994;90:649–652
  36. Warren RS , Yuan H , Matli MR , et al.   Induction of vascular endothelial growth factor by insulin-like growth factor 1 in colorectal carcinoma . J Biol Chem . 1996;271:29483–29488
  37. Soker S , Takashima S , Miao HQ , et al.   Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor . Cell . 1998;92:735–745
  38. Gluzman-Poltorak Z , Cohen T , Herzog Y , et al.   Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165 . J Biol Chem . 2000;275:18040–18045
  39. Strizzi L , Catalano A , Vianale G , et al.   Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma . J Pathol . 2001;193:468–475
  40. Bellamy WT , Richter L , Frutiger Y , et al.   Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies . Cancer Res . 1999;59:728–733
  41. Ferrer FA , Miller LJ , Lindquist R , et al.   Expression of vascular endothelial growth factor receptors in human prostate cancer . Urology . 1999;54:567–572
  42. Millauer B , Wizigmann-Voos S , Schnurch H , et al.   High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis . Cell . 1993;72:835–846
  43. Bernatchez PN , Soker S , Sirois MG . Vascular endothelial growth factor effect on endothelial cell proliferation, migration, and platelet-activating factor synthesis is Flk-1-dependent . J Biol Chem . 1999;274:31047–31054
  44. Gerber HP , McMurtrey A , Kowalski J , et al.   Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation . J Biol Chem . 1998;273:30336–30343
  45. Gille H , Kowalski J , Li B , et al.   Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2). A reassessment using novel receptor-specific vascular endothelial growth factor mutants . J Biol Chem . 2001;276:3222–3230
  46. Endo A , Fukuhara S , Masuda M , et al.   Selective inhibition of vascular endothelial growth factor receptor-2 (VEGFR-2) identifies a central role for VEGFR-2 in human aortic endothelial cell responses to VEGF . J Recept Signal Transduct Res . 2003;23:239–254
  47. Holash J , Davis S , Papadopoulos N , et al.   VEGF-Trap (A VEGF blocker with potent antitumor effects) . Proc Natl Acad Sci U S A . 2002;99:11393–11398
  48. Lin YS , Nguyen C , Mendoza JL , et al.   Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of a humanized monoclonal antibody against vascular endothelial growth factor . J Pharmacol Exp Ther . 1999;288:371–378
  49. Asano M , Yukita A , Matsumoto T , et al.   Inhibition of tumor growth and metastasis by an immunoneutralizing monoclonal antibody to human vascular endothelial growth factor/vascular permeability factor121 . Cancer Res . 1995;55:5296–5301
  50. Warren RS , Yuan H , Matli MR , et al.   Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis . J Clin Invest . 1995;95:1789–1797
  51. Kim KJ , Li B , Winer J , et al.   Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo . Nature . 1993;362:841–844
  52. Gordon MS , Margolin K , Talpaz M , et al.   Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer . J Clin Oncol . 2001;19:843–850
  53. Kabbinavar F , Hurwitz HI , Fehrenbacher L , et al.   Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer . J Clin Oncol . 2003;21:60–65
  54. Petrelli N , Douglass HO , Herrera L , et al.  Gastrointestinal Tumor Study Group   The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma (A prospective randomized phase III trial) . J Clin Oncol . 1989;7:1419–1426
  55. Novotny W , Hurwitz H , Fehrenbacher L , et al.   Bevacizumab demonstrates a survival benefit in all pre-specified patient subgroups . Proc Am Soc Clin Oncol GI Cancer Symp . 2004; (abstr 223)
  56. Hurwitz H , Fehrenbacher L , Hainsworth J , et al.   Bevacizumab in combination with 5-fluorouracil and leucovorin (A promising regimen for first-line metastatic colorectal cancer) . Proc Am Soc Clin Oncol GI Cancer Symp . 2004; (abstr 286)
  57. www.gene.com. Genetech Press Release, November, 25, 2003
  58. Koeppen HKW , Ince WL , Holmgren E , et al.   Molecular tumor characteristics and response to bevacizumab plus irinotecan/5-fluorouracil/leucovorin in metastatic colorectal cancer . 2004; Poster, 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics,
  59. Torosian MH , Turnbull AD . Emergency laparotomy for spontaneous intestinal and colonic perforations in cancer patients receiving corticosteroids and chemotherapy . J Clin Oncol . 1988;6:291–296
  60. Liaw CC , Huang JS , Wang HM , et al.   Spontaneous gastroduodenal perforation in patients with cancer receiving chemotherapy and steroids. Report of four cases combining 5-fluorouracil infusion and cisplatin with antiemetics dexamethasone . Cancer . 1993;72:1382–1385
  61. Giantonio BJ , Levy D , O’Dwyer PJ , et al.   Bevacizumab (anti-VEGF) plus IFL (irinotecan, fluorouracil, leucovorin) as front-line therapy for advanced colorectal cancer (advCRC) (Updated results from the Eastern Cooperative Oncology Group (ECOG) Study E2200) . Proc Am Soc Clin Oncol GI Cancer Symp . 2004; (abstr 289)
  62. Benson AB , Catalano PJ , Meropol NJ , et al.   Bevacizumab (anti-VEGF) plus FOLFOX4 in previously treated advanced colorectal cancer (advCRC) (An interim toxicity analysis of the Eastern Cooperative Oncology Group (ECOG) study E3200) . Proc Am Soc Clin Oncol . 2003;22:243; (abstr 975)
  63. http://www.cancer.gov, 12/01/04
  64. Wood JM , Bold G , Buchdunger E , et al.   PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration . Cancer Res . 2000;60:2178–2189
  65. Thomas AL , Morgan B , Drevs J , et al.   Vascular endothelial growth factor receptor tyrosine kinase inhibitors (PTK787/ZK 222584) . Semin Oncol . 2003;30:32–38
  66. Drevs J , Mross K , Fuxius S , et al.   A phase-1 dose-escalating and pharmacokinetic (PK) study of the VEGF-receptor-inhibitor PTK787/ZK222584 (PTK/ZK) in patients with liver metastasis of advanced cancer . Proc Am Soc Clin Oncol . 2001;20:100a; (abstr 398)
  67. Steward WB , Thomas AL , Morgan B , et al.   Extended phase I study of the oral vascular endothelial growth factor (VEGF) receptor inhibitor PTK787/ZK 222584 in combination with oxaliplatin/5-fluorouracil (5-FU)/leucovorin as first line treatment for metastatic colorectal cancer . Proc Am Soc Clin Oncol . 2003;22:274; (abstr 1098)
  68. Trarbach T , Schleucher N , Riedel U , et al.   Phase I study of the oral vascular endothelial growth factor (VEGF) receptor inhibitor PTK787/ZK 222584 (PTK/ZK) in combination with irinotecan/5-fluorouracil/leucovorin in patients with metastatic colorectal cancer . Proc Am Soc Clin Oncol . 2003;22:285; (abstr 1144)
  69. Morgan B , Thomas AL , Drevs J , et al.   Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases (results from two phase I studies) . J Clin Oncol . 2003;21:3955–3964
  70. Penning TD , Talley JJ , Bertenshaw SR , et al.   Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors (Identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze nesulfonamide (SC-58635, celecoxib)) . J Med Chem . 1997;40:1347–1365
  71. Masferrer JL , Leahy KM , Koki AT , et al.   Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors . Cancer Res . 2000;60:1306–1311
  72. Blanke C , Benson A , Dragovich T , et al.   A phase II trial of celecoxib (CX), irinotecan (I), 5-fluorouracil (5FU), and leucovorin (LCV) in patients (pts) with unresectable or metastatic colorectal cancer (CRC) . Proc Am Soc Clin Oncol . 2002;21:127a; (abstr 505)
  73. Pan C , Loehrer P , Juliar B , et al.   A phase II trial of irinotecan (I), 5-fluorouracil (F), leucovorin (L) (IFL), celecoxib and glutamine as first line therapy for advanced colorectal cancer (CRC) (A Hoosier Oncology Group study) . Proc Am Soc Clin Oncol . 2003;22:335; (abstr 1347)
  74. Haller DG . COX-2 inhibitors in oncology . Semin Oncol . 2003;30(suppl 12):2–8
  75. D’Amato RJ , Loughnan MS , Flynn E , et al.   Thalidomide is an inhibitor of angiogenesis . Proc Natl Acad Sci U S A . 1994;91:4082–4085
  76. Zwingenberger K , Wnendt S . Immunomodulation by thalidomide (Systematic review of the literature and of unpublished observations) . J Inflamm . 1995;46:177–211
  77. Dimopoulos MA , Anagnostopoulos A , Weber D . Treatment of plasma cell dyscrasias with thalidomide and its derivatives . J Clin Oncol . 2003;21:4444–4454
  78. Venook A , Hurwitz H , Cunningham C , et al.   Relationship of clinical outcome in metastatic colorectal carcinoma to levels of soluble VEGFR-1 (Results of a phase II trial of a ribozyme targeting the pre-mRNA of VEGFR-1 (angiozyme), in combination with chemotherapy) . Proc Am Soc Clin Oncol . 2003;22:256; (abstr 1025)
  79. Giantonio BJ , Levy D , O’Dwyer PJ , et al.   Bevacizumab (anti-VEGF) plus IFL (irinotecan, fluorouracil, leucovorin) as front-line therapy for advanced colorectal cancer (advCRC) (Results from the Eastern Cooperative Oncology Group (ECOG) study E2200) . Proc Am Soc Clin Oncol . 2003;22:255; (abstr 1024)
  80. http.//www.clinicaltrials.gov, 1/24/04
  81. Trarbach T , Thomas AL , Bartel C , et al.   Preliminary phase I results of the oral, once-daily angiogenesis inhibitor PTK787/ZK 222584 (PTK/ZK) in combination with chemotherapy for the treatment of metastatic colorectal cancer . Eur J Cancer . 2003;1(suppl):S91; (abstr)
  82. Weng DE , Usman N . Angiozyme (A novel angiogenesis inhibitor) . Curr Oncol Rep . 2001;3:141–146
  83. Hunt S . Technology evaluation (IMC-1C11, ImClone Systems) . Curr Opin Mol Ther . 2001;3:418–424
  84. Mendel DB , Laird AD , Xin X , et al.   In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors (Determination of a pharmacokinetic/pharmacodynamic relationship) . Clin Cancer Res . 2003;9:327–337
  85. Ciardiello F , Caputo R , Damiano V , et al.   Antitumor effects of ZD6474, a small molecule vascular endothelial growth factor receptor tyrosine kinase inhibitor, with additional activity against epidermal growth factor receptor tyrosine kinase . Clin Cancer Res . 2003;9:1546–1556
  86. Wedge SR , Ogilvie DJ , Dukes M , et al.   ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration . Cancer Res . 2002;62:4645–4655
  87. Dawson DW , Volpert OV , Pearce SF , et al.   Three distinct D-amino acid substitutions confer potent antiangiogenic activity on an inactive peptide derived from a thrombospondin-1 type 1 repeat . Mol Pharmacol . 1999;55:332–338
  88. O’reilly MS , Holmgren L , Shing Y , et al.   Angiostatin (A circulating endothelial cell inhibitor that suppresses angiogenesis and tumor growth) . Cold Spring Harb Symp Quant Biol . 1994;59:471–482
  89. Troyanovsky B , Levchenko T , Mansson G , et al.   Angiomotin (An angiostatin binding protein that regulates endothelial cell migration and tube formation) . J Cell Biol . 2001;152:1247–1254
  90. O’reilly MS , Boehm T , Shing Y , et al.   Endostatin (An endogenous inhibitor of angiogenesis and tumor growth) . Cell . 1997;88:277–285
  91. Hori K , Saito S . Microvascular mechanisms by which the combretastatin A-4 derivative AC7700 (AVE8062) induces tumour blood flow stasis . Br J Cancer . 2003;89:1334–1344
  92. Kanthou C , Tozer GM . The tumor vascular targeting agent combretastatin A-4-phosphate induces reorganization of the actin cytoskeleton and early membrane blebbing in human endothelial cells . Blood . 2002;99:2060–2069
  93. Davis PD , Dougherty GJ , Blakey DC , et al.   ZD6126 (A novel vascular-targeting agent that causes selective destruction of tumor vasculature) . Cancer Res . 2002;62:7247–7253
  94. Nakashima T , Hirano S , Agata N , et al.   Inhibition of angiogenesis by a new isocoumarin, NM-3 . J Antibiot (Tokyo) . 1999;52:426–428
  95. Reimer CL , Agata N , Tammam JG , et al.   Antineoplastic effects of chemotherapeutic agents are potentiated by NM-3, an inhibitor of angiogenesis . Cancer Res . 2002;62:789–795
  96. Ingber D , Fujita T , Kishimoto S , et al.   Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth . Nature . 1990;348:555–557

PII: S0093-7754(04)00455-5

doi: 10.1053/j.seminoncol.2004.09.026

Seminars in Oncology
Volume 32, Issue 1 , Pages 61-68 , February 2005

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