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Angiogenesis inhibitors: What is the clinical future?

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Advances in Targeted Cancer Therapy

Part of the book series: Progress in Drug Research ((PDR,volume 63))

Conclusion

In conclusion, because of the responses observed in phase I, II and III trials with angiogenesis inhibitors in combination with other biological agents or classic chemotherapy, there is no longer doubt that anti-angiogenic agents have become part of anticancer therapy in general. In the coming years, we should further explore the treatment strategies in which anti-angiogenic agents will add to a prolonged survival and an increase in the cure rate of cancer. In our opinion, the contribution of these agents will be tremendous.

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References

  1. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285: 1182–1186

    CAS  PubMed  Google Scholar 

  2. Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1: 27–31

    Article  CAS  PubMed  Google Scholar 

  3. Distler JH, Hirth A, Kurowska-Stolarska M, Gay RE, Gay S, Distler O (2003) Angiogenic and angiostatic factors in the molecular control of angiogenesis. Q J Nucl Med 47: 149–161

    CAS  PubMed  Google Scholar 

  4. Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, Meli S, Gasparini G (1992) Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 84: 1875–1887

    CAS  PubMed  Google Scholar 

  5. Weidner F (1979) Comparative histological studies of regional lymph nodes of 201 melanoma patients. (Microscopic features in relation to individual age, site, and metastatic spread). Arch Dermatol Res 266: 161–175

    Article  CAS  PubMed  Google Scholar 

  6. Hasan J, Byers R, Jayson GC (2002) Intra-tumoural microvessel density in human solid tumours. Br J Cancer 86: 1566–1577

    Article  CAS  PubMed  Google Scholar 

  7. Gasparini G, Toi M, Gion M, Verderio P, Dittadi R, Hanatani M, Matsubara I, Vinante O, Bonoldi E, Boracchi P et al (1997) Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst 89: 139–147

    Article  CAS  PubMed  Google Scholar 

  8. Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86: 353–364

    Article  CAS  PubMed  Google Scholar 

  9. Ribatti D, Vacca A, Presta M (2000) The discovery of angiogenic factors: a historical review. Gen Pharmacol 35: 227–231

    CAS  PubMed  Google Scholar 

  10. Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267: 10931–10934

    CAS  PubMed  Google Scholar 

  11. Kenyon BM, Voest EE, Chen CC, Flynn E, Folkman J, D’Amato RJ (1996) A model of angiogenesis in the mouse cornea. Invest Ophthalmol Vis Sci 37: 1625–1632

    CAS  PubMed  Google Scholar 

  12. Good DJ, Polverini PJ, Rastinejad F, Le Beau MM, Lemons RS, Frazier WA, Bouck NP (1990) A tumor suppressor-dependent inhibitor of angiogenesis in immunologically and functionally indistinguishable from a fragment of thromospondin. Proc Natl Acad Sci USA 87: 664–6628

    Google Scholar 

  13. Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407: 249–257

    Article  CAS  PubMed  Google Scholar 

  14. O’Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J (1997) Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88: 277–285

    Google Scholar 

  15. Hamby JM, Showalter HD (1999) Small molecule inhibitors of tumor-promoted angiogenesis, including protein tyrosine kinase inhibitors. Pharmacol Ther 82: 169–193

    Article  CAS  PubMed  Google Scholar 

  16. Folkman J (1996) New perspectives in clinical oncology from angiogenesis research. Eur J Cancer 32A: 2534–2539

    Article  Google Scholar 

  17. Folkman J, Watson K, Ingber D, Hanahan D (1989) Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 339: 58–61

    Article  CAS  PubMed  Google Scholar 

  18. Udagawa T, Fernandez A, Achilles EG, Folkman J, D’Amato RJ (2002) Persistence of microscopic human cancers in mice: alterations in the angiogenic balance accompanies loss of tumor dormancy. FASEB J 16: 1361–1370

    Article  CAS  PubMed  Google Scholar 

  19. Holmgren L, O’Reilly MS, Folkman J (1995) Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1: 149–153

    Article  CAS  PubMed  Google Scholar 

  20. Norton JD (2000) ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis. J Cell Sci 113: 3897–3905

    CAS  PubMed  Google Scholar 

  21. Lyden D, Young AZ, Zagzag D, Yan W, Gerald W, O’Reilly R, Bader BL, Hynes RO, Zhuang Y, Manova K et al (1999) Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature 401: 670–677

    Article  CAS  PubMed  Google Scholar 

  22. Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, Chadburn A, Heissig B, Marks W, Witte L et al (2001) Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 7: 1194–1201

    Article  CAS  PubMed  Google Scholar 

  23. Volpert OV, Pili R, Sikder HA, Nelius T, Zaichuk T, Morris C, Shiflett CB, Devlin MK, Conant K, Alani RM (2002) Id1 regulates angiogenesis through transcriptional repression of thrombospondin-1. Cancer Cell 2: 473–483

    Article  CAS  PubMed  Google Scholar 

  24. Shi Q, Le X, Wang B, Abbruzzese JL, Xiong Q, He Y, Xie K (2001) Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells. Oncogene 20: 3751–3756

    CAS  PubMed  Google Scholar 

  25. Shima DT, Adamis AP, Ferrara N, Yeo KT, Yeo TK, Allende R, Folkman J, D’Amore PA (1995) Hypoxic induction of endothelial cell growth factors in retinal cells: identification and characterization of vascular endothelial growth factor (VEGF) as the mitogen. Mol Med 1: 182–193

    CAS  PubMed  Google Scholar 

  26. Satake S, Kuzuya M, Miura H, Asai T, Ramos MA, Muraguchi M, Ohmoto Y, Iguchi A (1998) Up-regulation of vascular endothelial growth factor in response to glucose deprivation. Biol Cell 90: 161–168

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  28. Hahn WC, Weinberg RA (2002) Rules for making human tumor cells. N Engl J Med 347: 1593–1603

    Article  CAS  PubMed  Google Scholar 

  29. Sporn MB (1997) The war on cancer: a review. Ann N Y Acad Sci 833: 137–146

    CAS  PubMed  Google Scholar 

  30. Verheul HMW, Pinedo HM (1998) Clinical implications of drug resistance. In: HM Pinedo, G Giaccone (eds):. Cambridge University Press, Cambridge, 199–232

    Google Scholar 

  31. Demicheli R, Terenziani M, Valagussa P, Moliterni A, Zambetti M, Bonadonna G (1994) Local recurrences following mastectomy: support for the concept of tumor dormancy. J Natl Cancer Inst 86: 45–48

    CAS  PubMed  Google Scholar 

  32. Demicheli R (2001) Tumour dormancy: findings and hypotheses from clinical research on breast cancer. Semin Cancer Biol 11: 297–306

    Article  CAS  PubMed  Google Scholar 

  33. van’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415: 530–536

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  35. 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: 1979–1986

    Article  CAS  PubMed  Google Scholar 

  36. Margolin K, Gordon MS, Holmgren E, Gaudreault J, Novotny W, Fyfe G, Adelman D, Stalter S, Breed J (2001) 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 Oncol 19: 851–856

    CAS  PubMed  Google Scholar 

  37. Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G, Griffing S, Bergsland E (2003) Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21: 60–65

    CAS  PubMed  Google Scholar 

  38. 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: 427–434

    Article  CAS  PubMed  Google Scholar 

  39. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 305: 2335–2342

    Google Scholar 

  40. Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT, Chung DC, Sahani DV, Kalva SP, Kozin SV et al (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10: 145–147

    CAS  PubMed  Google Scholar 

  41. Ramaswamy B, Shapiro CL (2003) Phase II trial of bevacizumab in combination with docetaxel in women with advanced breast cancer. Clin Breast Cancer 4: 292–294

    CAS  PubMed  Google Scholar 

  42. Chen HX (2004) Expanding the clinical development of bevacizumab. Oncologist 9Suppl 1: 27–35

    CAS  PubMed  Google Scholar 

  43. Jayson GC, Zweit J, Jackson A, Mulatero C, Julyan P, Ranson M, Broughton L, Wagstaff J, Hakannson L, Groenewegen G et al (2002) Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: implications for trial design of antiangiogenic antibodies. J Natl Cancer Inst 94: 1484–1493

    CAS  PubMed  Google Scholar 

  44. Asano M, Yukita A, Suzuki H (1999) Wide spectrum of antitumor activity of a neutralizing monoclonal antibody to human vascular endothelial growth factor. Jpn J Cancer Res 90: 93–100

    CAS  PubMed  Google Scholar 

  45. Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E et al (2002) VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA 99: 11393–11398

    Article  CAS  PubMed  Google Scholar 

  46. Huang J, Frischer JS, Serur A, Kadenhe A, Yokoi A, McCrudden KW, New T, O’Toole K, Zabski S, Rudge JS et al (2003) Regression of established tumors and metastases by potent vascular endothelial growth factor blockade. Proc Natl Acad Sci USA 100: 7785–7790

    CAS  PubMed  Google Scholar 

  47. Byrne AT, Ross L, Holash J, Nakanishi M, Hu L, Hofmann JI, Yancopoulos GD, Jaffe RB (2003) Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. Clin Cancer Res 9: 5721–5728

    CAS  PubMed  Google Scholar 

  48. Dupont J, Schwartz L, Koutcher J, Spriggs D, Gordon M, Mendelson D, Murren J, Lucarelli A, Cedarbaum J (2004) Phase I and pharmacokinetic study of VEGF trap administered subcutaneously to patients with advanced solid malignancies. Proc Am Soc Clin Oncol 23: abstr. 3009

    Google Scholar 

  49. Hunt S (2001) Technology evaluation: IMC-1C11, ImClone Systems. Curr Opin Mol Ther 3: 418–424

    CAS  PubMed  Google Scholar 

  50. Wang ES, Teruya-Feldstein J, Wu Y, Zhu Z, Hicklin D, Moore MA (2004) Targeting autocrine and paracrine VEGF receptor pathways inhibits human lymphoma xenografts in vivo. Blood; in press

    Google Scholar 

  51. Posey JA, Ng TC, Yang B, Khazaeli MB, Carpenter MD, Fox F, Needle M, Waksal H, LoBuglio AF (2003) A phase I study of anti-kinase insert domain-containing receptor antibody, IMC-1C11, in patients with liver metastases from colorectal carcinoma. Clin Cancer Res 9: 1323–1332

    CAS  PubMed  Google Scholar 

  52. Vajkoczy P, Menger MD, Vollmar B, Schilling L, Schmiedek P, Hirth KP, Ullrich A, Fong TA (1999) Inhibition of tumor growth, angiogenesis, and microcirculation by the novel Flk-1 inhibitor SU5416 as assessed by intravital multi-fluorescence videomicroscopy. Neoplasia 1: 31–41

    CAS  PubMed  Google Scholar 

  53. Kuenen BC, Rosen L, Smit EF, Parson MR, Levi M, Ruijter R, Huisman H, Kedde MA, Noordhuis P, van der Vijgh WJ et al (2002) Dose-finding and pharmacokinetic study of cisplatin, gemcitabine, and SU5416 in patients with solid tumors. J Clin Oncol 20: 1657–1667

    Article  CAS  PubMed  Google Scholar 

  54. Laird AD, Vajkoczy P, Shawver LK, Thurnher A, Liang C, Mohammadi M, Schlessinger J, Ullrich A, Hubbard SR, Blake RA et al (2000) SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res 60: 4152–4160

    CAS  PubMed  Google Scholar 

  55. O’Farrell AM, Abrams TJ, Yuen HA, Ngai TJ, Louie SG, Yee KW, Wong LM, Hong W, Lee LB, Town A et al (2003) SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 101: 3597–3605

    Google Scholar 

  56. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB, Murray LJ et al (2003) 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 9: 327–337

    CAS  PubMed  Google Scholar 

  57. Yee KW, Schittenhelm M, O’Farrell AM, Town AR, McGreevey L, Bainbridge T, Cherrington JM, Heinrich MC (2004) Synergistic effect of SU11248 with Cytarabine or Daunorubicin on FLT3-ITD positive leukemic cells. Blood 104: 4202–4209

    Article  CAS  PubMed  Google Scholar 

  58. Murray LJ, Abrams TJ, Long KR, Ngai TJ, Olson LM, Hong W, Keast PK, Brassard JA, O’Farrell AM, Cherrington JM et al (2003) SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. Clin Exp Metastasis 20: 757–766

    Article  CAS  PubMed  Google Scholar 

  59. O’Farrell AM, Foran JM, Fiedler W, Serve H, Paquette RL, Cooper MA, Yuen HA, Louie SG, Kim H, Nicholas S et al (2003) An innovative phase I clinical study demonstrates inhibition of FLT3 phosphorylation by SU11248 in acute myeloid leukemia patients. Clin Cancer Res 9: 5465–5476

    Google Scholar 

  60. Fiedler W, Serve H, Dohner H, Schwittay M, Ottmann OG, O’Farrell AM, Bello CL, Allred R, Manning WC, Cherrington JM et al (2004) A phase I study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease. Blood 105: 986–993

    Article  PubMed  Google Scholar 

  61. Demetri GD, Desai J, Fletcher JA, Morgan JA, Fletcher CDM, Kazanovicz A, Van Den Abbeele A, Baum C, Maki R, Heinrich MC (2004) SU11248, a multi-targeted tyrosine kinase inhibitor, can overcome imatinib (IM) resistance caused by diverse genomic mechanisms in patients (pts) with metastatic gastrointestinal stromal tumor (GIST). Proc Am Soc Clin Oncol 23: abstr. 3001

    Google Scholar 

  62. Motzer RJ, Rini BI, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, Zhu J, Kim ST, Baum C (2004) SU011248, a novel tyrosine kinase inhibitor, shows antitumor activity in second-line therapy for patients with metastatic renal cell carcinoma: Results of a phase 2 trial. Proc Am Soc Clin Oncol 23: abstr. 4500

    Google Scholar 

  63. Drevs J, Muller-Driver R, Wittig C, Fuxius S, Esser N, Hugenschmidt H, Konerding MA, Allegrini PR, Wood J, Hennig J et al (2002) PTK787/ZK 222584, a specific vascular endothelial growth factor-receptor tyrosine kinase inhibitor, affects the anatomy of the tumor vascular bed and the functional vascular properties as detected by dynamic enhanced magnetic resonance imaging. Cancer Res 62: 4015–4022

    CAS  PubMed  Google Scholar 

  64. Morgan B, Thomas AL, Drevs J, Hennig J, Buchert M, Jivan A, Horsfield MA, Mross K, Ball HA, Lee L et al (2003) 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 21: 3955–3964

    Article  CAS  PubMed  Google Scholar 

  65. Wedge SR, Ogilvie DJ, Dukes M, Kendrew J, Chester R, Jackson JA, Boffey SJ, Valentine PJ, Curwen JO, Musgrove HL et al (2002) ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res 62: 4645–4655

    CAS  PubMed  Google Scholar 

  66. Bates D (2003) ZD-6474. AstraZeneca. Curr Opin Investig Drugs 4: 1468–1472

    CAS  PubMed  Google Scholar 

  67. Medinger M, Mross K, Zirrgiebel U, Strecker R, Wheeler C, Clack G, Lewis J, Puchalski TA, Unger C, Drevs J (2004) Phase I dose escalating study of the highly potent VEGF receptor kinase inhibitor, azd2171, in patients with advanced cancers with liver metastases. Proc Am Soc Clin Oncol 23: abstr. 3055

    Google Scholar 

  68. Ruggeri B, Singh J, Gingrich D, Angeles T, Albom M, Yang S, Chang H, Robinson C, Hunter K, Dobrzanski P et al (2003) CEP-7055: a novel, orally active pan inhibitor of vascular endothelial growth factor receptor tyrosine kinases with potent antiangiogenic activity and antitumor efficacy in preclinical models. Cancer Res 63: 5978–5991

    CAS  PubMed  Google Scholar 

  69. Pili R, Carducci M, Robertson PA (2003) Phase I study of the pan-VEGR tyrosine kinase inhibitor, CEP-7055, in patients with advanced malignancy. Proc Am Soc Clin Oncol 22: 207

    Google Scholar 

  70. Pavco PA, Bouhana KS, Gallegos AM, Agrawal A, Blanchard KS, Grimm SL, Jensen KL, Andrews LE, Wincott FE, Pitot PA et al (2000) Antitumor and antimetastatic activity of ribozymes targeting the messenger RNA of vascular endothelial growth factor receptors. Clin Cancer Res 6: 2094–2103

    CAS  PubMed  Google Scholar 

  71. Weng DE, Usman N (2001) Angiozyme: a novel angiogenesis inhibitor. Curr Oncol Rep 3: 141–146

    CAS  PubMed  Google Scholar 

  72. Sandberg JA, Parker VP, Blanchard KS, Sweedler D, Powell JA, Kachensky A, Bellon L, Usman N, Rossing T, Borden E et al (2000) Pharmacokinetics and tolerability of an antiangiogenic ribozyme (ANGIOZYME) in healthy volunteers. J Clin Pharmacol 40: 1462–1469

    CAS  PubMed  Google Scholar 

  73. Venook A, Hurwitz A, Cunningham BC (2003) Relationship of clinical outcome in metastatic colorectal carcinoma to levels of soluble VEGFR-1: results of a phase II trial of a ribozyme targeting pre-mRNA of VEGR-1 (angiozyme), in combination with chemotherapy. Proc Am Soc Clin Oncol 22: 256

    Google Scholar 

  74. O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J (1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79: 315–328

    Google Scholar 

  75. Thomas JP, Arzoomanian RZ, Alberti D, Marnocha R, Lee F, Friedl A, Tutsch K, Dresen A, Geiger P, Pluda J et al (2003) Phase I pharmacokinetic and pharmacodynamic study of recombinant human endostatin in patients with advanced solid tumors. J Clin Oncol 21: 223–231

    CAS  PubMed  Google Scholar 

  76. Boehm T, Folkman J, Browder T, O’Reilly MS (1997) Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 390, 404–407

    Article  CAS  PubMed  Google Scholar 

  77. Westphal JR (2004) Technology evaluation: ABT-510, Abbott. Curr Opin Mol Ther 6: 451–457

    CAS  PubMed  Google Scholar 

  78. Nor JE, Mitra RS, Sutorik MM, Mooney DJ, Castle VP, Polverini PJ (2000) Thrombospondin-1 induces endothelial cell apoptosis and inhibits angiogenesis by activating the caspase death pathway. J Vasc Res 37: 209–218

    CAS  PubMed  Google Scholar 

  79. Reijerkerk A, Voest EE, Gebbink MF (2000) No grip, no growth: the conceptual basis of excessive proteolysis in the treatment of cancer. Eur J Cancer 36: 1695–1705

    Article  CAS  PubMed  Google Scholar 

  80. Patel SR, Jenkins J, Papadopolous N, Burgess MA, Plager C, Gutterman J, Benjamin RS (2001) Pilot study of vitaxin-an angiogenesis inhibitor-in patients with advanced leiomyosarcomas. Cancer 92: 1347–1348

    Article  CAS  PubMed  Google Scholar 

  81. Posey JA, Khazaeli MB, DelGrosso A, Saleh MN, Lin CY, Huse W, LoBuglio AF (2001) A pilot trial of Vitaxin, a humanized anti-vitronectin receptor (anti-alpha v beta 3) antibody in patients with metastatic cancer. Cancer Biother Radiopharm 16: 125–132

    Article  CAS  PubMed  Google Scholar 

  82. Burke PA, DeNardo SJ, Miers LA, Lamborn KR, Matzku S, DeNardo GL (2002) Cilengitide targeting of alpha(v)beta(3) integrin receptor synergizes with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts. Cancer Res 62: 4263–4272

    CAS  PubMed  Google Scholar 

  83. Eskens FA, Dumez H, Hoekstra R, Perschl A, Brindley C, Bottcher S, Wynendaele W, Drevs J, Verweij J, van Oosterom AT (2003) Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of Cilengitide (EMD 121974), a novel inhibitor of the integrins alphavbeta3 and alphavbeta5 in patients with advanced solid tumours. Eur J Cancer 39: 917–926

    Article  CAS  PubMed  Google Scholar 

  84. Raguse JD, Gath HJ, Bier J, Riess H, Oettle H (2004) Cilengitide (EMD 121974) arrests the growth of a heavily pretreated highly vascularised head and neck tumour. Oral Oncol 40: 228–230

    Article  CAS  PubMed  Google Scholar 

  85. Kumar S, Witzig TE, Rajkumar SV (2004) Thalidomide: current role in the treatment of non-plasma cell malignancies. J Clin Oncol 22: 2477–2488

    CAS  PubMed  Google Scholar 

  86. D’Amato RJ, Loughnan MS, Flynn E, Folkman J (1994) Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 91: 4082–4085

    Google Scholar 

  87. Verheul HM, Panigrahy D, Yuan J, D’Amato RJ (1999) Combination oral antiangiogenic therapy with thalidomide and sulindac inhibits tumour growth in rabbits. Br J Cancer 79: 114–118

    Article  CAS  PubMed  Google Scholar 

  88. Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeddis J, Barlogie B (1999) Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 134: 1565–1571

    Google Scholar 

  89. Sills AK Jr, Williams JI, Tyler BM, Epstein DS, Sipos EP, Davis JD, McLane MP, Pitchford S, Cheshire K, Gannon FH et al (1998) Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature. Cancer Res 58: 2784–2792

    CAS  PubMed  Google Scholar 

  90. Hao D, Hammond LA, Eckhardt SG, Patnaik A, Takimoto CH, Schwartz GH, Goetz AD, Tolcher AW, McCreery HA, Mamun K et al (2003) A Phase I and pharmacokinetic study of squalamine, an aminosterol angiogenesis inhibitor. Clin Cancer Res 9: 2465–2471

    CAS  PubMed  Google Scholar 

  91. Keyes KA, Mann L, Sherman M, Galbreath E, Schirtzinger L, Ballard D, Chen YF, Iversen P, Teicher BA (2004) LY3176 15 decreases plasma VEGF levels in human tumor xenograft-bearing mice. Cancer Chemother Pharmacol 53: 133–140

    Article  CAS  PubMed  Google Scholar 

  92. Kuenen BC (2003) Analysis of prothrombotic mechanisms and endothelial perturbation during treatment with angiogenesis inhibitors. Pathophysiol Haemost Thromb 33Suppl 1: 13–14

    PubMed  Google Scholar 

  93. Zangari M, Barlogie B, Thertulien R, Jacobson J, Eddleman P, Fink L, Fassas A, Van Rhee F, Talamo G, Lee CK et al (2003) Thalidomide and deep vein thrombosis in multiple myeloma: risk factors and effect on survival. Clin Lymphoma 4: 32–35

    CAS  PubMed  Google Scholar 

  94. Cobleigh MA, Langmuir VK, Sledge GW, Miller KD, Haney L, Novotny WF, Reimann JD, Vassel A (2003) A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 30: 117–124

    Article  CAS  PubMed  Google Scholar 

  95. Kiefer FN, Neysari S, Humar R, Li W, Munk VC, Battegay EJ (2003) Hypertension and angiogenesis. Curr Pharm Des 9: 1733–1744

    Article  CAS  PubMed  Google Scholar 

  96. Xu Y, Wahner AE, Nguyen PL (2004) Progression of chronic myeloid leukemia to blast crisis during treatment with imatinib mesylate. Arch Pathol Lab Med 128: 980–985

    PubMed  Google Scholar 

  97. Sullivan DC, Bicknell R (2003) New molecular pathways in angiogenesis. Br J Cancer 89: 228–231

    Article  CAS  PubMed  Google Scholar 

  98. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350: 2129–2139

    Article  CAS  PubMed  Google Scholar 

  99. Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22: 1201–1208

    Article  CAS  PubMed  Google Scholar 

  100. Weinstein MC, Goldie SJ, Losina E, Cohen CJ, Baxter JD, Zhang H, Kimmel AD, Freedberg KA (2001) Use of genotypic resistance testing to guide hiv therapy: clinical impact and cost-effectiveness. Ann Intern Med 134: 440–450

    CAS  PubMed  Google Scholar 

  101. Dickler MN, Rugo HS, Caravelli J, Brogi E, Sachs D, Panageas KS, Flores S, Moasser L, Norton L, Hudis C (2004) Phase II trial of erlotinib (OSI-774), an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, and bevacizumab, a recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF), in patients with metastatic breast cancer. Proc Am Soc Clin Oncol 23: abstr. 2001

    Google Scholar 

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Authors and Affiliations

  1. Department of Medical Oncology, Johns Hopkins University, 1650 Orleans Street CRB 162, Baltimore, MD, 21231, USA

    Henk M. W. Verheul

  2. VUmc Cancer Center Amsterdam, PO Box 7057, 1007, MB Amsterdam, The Netherlands

    Herbert M. Pinedo

Authors
  1. Henk M. W. Verheul
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  2. Herbert M. Pinedo
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Editors and Affiliations

  1. Novartis International AG, CH-4002, Basel, Switzerland

    Paul L. Herrling

  2. Novartis Institute for Tropical Diseases, 10 Biopolis Road, #05-01 Chromos, Singapore, 138670, Singapore

    Alex Matter M.D. (Director) (Director)

  3. 6551 Shelbyville Rd., Indianapolis, IN, 46237, USA

    Richard M. Schultz

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© 2005 Birkhäuser Verlag, Basel (Switzerland)

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Verheul, H.M.W., Pinedo, H.M. (2005). Angiogenesis inhibitors: What is the clinical future?. In: Herrling, P.L., Matter, A., Schultz, R.M. (eds) Advances in Targeted Cancer Therapy. Progress in Drug Research, vol 63. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7414-4_4

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