Carcinogenesis, Vol. 21, No. 3, 505-515,
March 2000
© 2000 Oxford University Press
Cancer Biology |
Tumor angiogenesis: past, present and the near future
Sunnybrook and Women's College Health Sciences Centre, Division of Cancer Biology Research, S-218 Research Building, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada
The concept of treating solid tumors by inhibiting tumor angiogenesis was first articulated almost 30 years ago. For the next 10 years it attracted little scientific interest. This situation changed, relatively slowly, over the succeeding decade with the discovery of the first pro-angiogenic molecules such as basic fibroblast growth factor and vascular endothelial growth factor (VEGF), and the development of methods of successfully growing vascular endothelial cells in culture as well as in vivo assays of angiogenesis. However, the 1990s have witnessed a striking change in both attitude and interest in tumor angiogenesis and anti-angiogenic drug development, to the point where a remarkably diverse group of over 24 such drugs is currently undergoing evaluation in phase I, II or III clinical trials. In this review I will discuss the many reasons for this. These features, together with other recent discoveries have created intense interest in initiating and expanding anti-angiogenic drug discovery programs in both academia and industry, and the testing of such newly developed drugs, either alone, or in various combinations with conventional cytotoxic therapeutics. However, significant problems remain in the clinical application of angiogenesis inhibitors such as the need for surrogate markers to monitor the effects of such drugs when they do not cause tumor regressions, and the design of clinical trials. Also of concern is that the expected need to use anti-angiogenic drugs chronically will lead to delayed toxic side effects in humans, which do not appear in rodents, especially in short-term studies.
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H. Seno, M. Oshima, T.-o Ishikawa, H. Oshima, K. Takaku, T. Chiba, S. Narumiya, and M. M. Taketo Cyclooxygenase 2- and Prostaglandin E2 Receptor EP2-dependent Angiogenesis in Apc{Delta}716 Mouse Intestinal Polyps Cancer Res., January 1, 2002; 62(2): 506 - 511. [Abstract] [Full Text] [PDF]
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G. Gannon, S. J. Mandriota, L. Cui, D. Baetens, M. S. Pepper, and G. Christofori Overexpression of Vascular Endothelial Growth Factor-A165 Enhances Tumor Angiogenesis but not Metastasis during {beta}-Cell Carcinogenesis Cancer Res., January 1, 2002; 62(2): 603 - 608. [Abstract] [Full Text] [PDF]
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T. P. Quinn, S. J. Soifer, K. Ramer, L. T. Williams, and M. C. Nakamura A Receptor for Vascular Endothelial Growth Factor That Stimulates Endothelial Apoptosis Cancer Res., December 1, 2001; 61(24): 8629 - 8637. [Abstract] [Full Text] [PDF]
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C. Mundhenke, J. P. Thomas, G. Wilding, F. T. Lee, F. Kelzc, R. Chappell, R. Neider, L. A. Sebree, and A. Friedl Tissue Examination to Monitor Antiangiogenic Therapy: A Phase I Clinical Trial with Endostatin Clin. Cancer Res., November 1, 2001; 7(11): 3366 - 3374. [Abstract] [Full Text] [PDF]
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J. C. Rodriguez-Manzaneque, T. F. Lane, M. A. Ortega, R. O. Hynes, J. Lawler, and M. L. Iruela-Arispe Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor PNAS, October 12, 2001; (2001) 171460498. [Abstract] [Full Text] [PDF]
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R. S. Kerbel Clinical Trials of Antiangiogenic Drugs: Opportunities, Problems, and Assessment of Initial Results J. Clin. Oncol., September 15, 2001; 19(90001): 45s - 51. [Full Text] [PDF]
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E. B. Carson-Walter, D. N. Watkins, A. Nanda, B. Vogelstein, K. W. Kinzler, and B. St. Croix Cell Surface Tumor Endothelial Markers Are Conserved in Mice and Humans Cancer Res., September 1, 2001; 61(18): 6649 - 6655. [Abstract] [Full Text] [PDF]
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 C. Halin, L. Zardi, and D. Neri Antibody-Based Targeting of Angiogenesis Physiology, August 1, 2001; 16(4): 191 - 194. [Abstract] [Full Text] [PDF]
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L. Sun, M. Vitolo, and A. Passaniti Runt-related Gene 2 in Endothelial Cells: Inducible Expression and Specific Regulation of Cell Migration and Invasion Cancer Res., July 1, 2001; 61(13): 4994 - 5001. [Abstract] [Full Text] [PDF]
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P. J. Mahasreshti, J. G. Navarro, M. Kataram, M. H. Wang, D. Carey, G. P. Siegal, M. N. Barnes, D. M. Nettelbeck, R. D. Alvarez, A. Hemminki, et al. Adenovirus-mediated Soluble FLT-1 Gene Therapy for Ovarian Carcinoma Clin. Cancer Res., July 1, 2001; 7(7): 2057 - 2066. [Abstract] [Full Text] [PDF]
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T. L. Moser, D. J. Kenan, T. A. Ashley, J. A. Roy, M. D. Goodman, U. K. Misra, D. J. Cheek, and S. V. Pizzo Endothelial cell surface F1-FO ATP synthase is active in ATP synthesis and is inhibited by angiostatin PNAS, May 24, 2001; (2001) 131067798. [Abstract] [Full Text] [PDF]
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F. Cavallo, E. Quaglino, L. Cifaldi, E. Di Carlo, A. André, P. Bernabei, P. Musiani, G. Forni, and R. A. Calogero Interleukin 12-activated Lymphocytes Influence Tumor Genetic Programs Cancer Res., April 1, 2001; 61(8): 3518 - 3523. [Abstract] [Full Text]
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A. K. Sood, E. A. Seftor, M. S. Fletcher, L. M. G. Gardner, P. M. Heidger, R. E. Buller, R. E. B. Seftor, and M. J. C. Hendrix Molecular Determinants of Ovarian Cancer Plasticity Am. J. Pathol., April 1, 2001; 158(4): 1279 - 1288. [Abstract] [Full Text] [PDF]
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 E. Y. Lin, A. V. Nguyen, R. G. Russell, and J. W. Pollard Colony-stimulating Factor 1 Promotes Progression of Mammary Tumors to Malignancy J. Exp. Med., March 19, 2001; 193(6): 727 - 740. [Abstract] [Full Text] [PDF]
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D. J. Brat and E. G. Van Meir Glomeruloid Microvascular Proliferation Orchestrated by VPF/VEGF : A New World of Angiogenesis Research Am. J. Pathol., March 1, 2001; 158(3): 789 - 796. [Full Text] [PDF]
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 G. L. Beatty and Y. Paterson IFN-{{gamma}}-Dependent Inhibition of Tumor Angiogenesis by Tumor-Infiltrating CD4+ T Cells Requires Tumor Responsiveness to IFN-{{gamma}} J. Immunol., February 15, 2001; 166(4): 2276 - 2282. [Abstract] [Full Text] [PDF]
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F. Nilsson, H. Kosmehl, L. Zardi, and D. Neri Targeted Delivery of Tissue Factor to the ED-B Domain of Fibronectin, a Marker of Angiogenesis, Mediates the Infarction of Solid Tumors in Mice Cancer Res., January 1, 2001; 61(2): 711 - 716. [Abstract] [Full Text]
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 B. St. Croix, C. Rago, V. Velculescu, G. Traverso, K. E. Romans, E. Montgomery, A. Lal, G. J. Riggins, C. Lengauer, B. Vogelstein, et al. Genes Expressed in Human Tumor Endothelium Science, August 18, 2000; 289(5482): 1197 - 1202. [Abstract] [Full Text]
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 C. Dong and P. J. Goldschmidt-Clermont Bone Sialoprotein and the Paradox of Angiogenesis Versus Atherosclerosis Circ. Res., April 28, 2000; 86(8): 827 - 828. [Full Text] [PDF]
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V. B. Lokeshwar and M. G. Selzer Differences in Hyaluronic Acid-mediated Functions and Signaling in Arterial, Microvessel, and Vein-derived Human Endothelial Cells J. Biol. Chem., September 1, 2000; 275(36): 27641 - 27649. [Abstract] [Full Text] [PDF]
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R. Colavitti, G. Pani, B. Bedogni, R. Anzevino, S. Borrello, J. Waltenberger, and T. Galeotti Reactive Oxygen Species as Downstream Mediators of Angiogenic Signaling by Vascular Endothelial Growth Factor Receptor-2/KDR J. Biol. Chem., January 25, 2002; 277(5): 3101 - 3108. [Abstract] [Full Text] [PDF]
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T. L. Moser, D. J. Kenan, T. A. Ashley, J. A. Roy, M. D. Goodman, U. K. Misra, D. J. Cheek, and S. V. Pizzo Endothelial cell surface F1-FO ATP synthase is active in ATP synthesis and is inhibited by angiostatin PNAS, June 5, 2001; 98(12): 6656 - 6661. [Abstract] [Full Text] [PDF]
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J. C. Rodriguez-Manzaneque, T. F. Lane, M. A. Ortega, R. O. Hynes, J. Lawler, and M. L. Iruela-Arispe Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor PNAS, October 23, 2001; 98(22): 12485 - 12490. [Abstract] [Full Text] [PDF]
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