Seminars in Radiation Oncology
Volume 13, Issue 1 , Pages 53-61 , January 2003

Targeting the tumor blood vessel network to enhance the efficacy of radiation therapy

References 

  1. Tobias J. Clinical practice of radiotherapy. Lancet. 1992;339:159–164
  2. DeVita VT, Hellman S, Rosenberg S. Cancer: Principles and practice of oncology. Philadelphia: Lippincott-Raven; 1997;
  3. Ausprunk D, Folkman J. Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res. 1977;14:53–65
  4. Folkman J. How is blood vessel growth regulated in normal and neoplastic tissue?. Cancer Res. 1986;46:467–473
  5. Hahnfeldt P, Panigrahy D, Folkman J, et al.  Tumor development under angiogenic signaling: A dynamical theory of tumor growth, treatment response, and postvascular dormancy. Cancer Res. 1999;59:4770–4775
  6. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1:27–31
  7. Risau W. Mechanisms of angiogenesis. Nature. 1997;386:671–674
  8. Siemeister G, Martiny-Baron G, Marme D. The pivotal role of VEGF in tumor angiogenesis: Molecular facts and therapeutic opportunities. Cancer Metastasis Rev. 1998;17:241–248
  9. Tannock IF. Population kinetics of carcinoma cells, capillary endothelial cells, and fibroblasts in a transplanted mouse mammary tumor. Cancer Res. 1970;30:2470–2477
  10. van Hinsbergh VW, Collen A, Koolwijk P. Angiogenesis and anti-angiogenesis: Perspectives for the treatment of solid tumors. Ann Oncol. 1999;4(Suppl):60–63
  11. Molema G, Meijer DK, de Leij LF. Tumor vasculature targeted therapies: Getting the players organized. Biochem Pharmacol. 1998;55:1939–1945
  12. Less JR, Skalak TC, Sevick EM, Jain RK. Microvascular architecture in a mammary carcinoma: Branching patterns and vessel dimensions. Cancer Res. 1991;51:265–273
  13. Vaupel P, Kallinowski F, Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: A review. Cancer Res. 1989;49:6449–6465
  14. Vaupel P, Thews O, Hoeckel M. Tumor oxygenation: characterization and clinical implications. In:  Smyth JF,  Boogaerts MA,  Ehmer BR editor. rhErythropoietin in cancer supportive treatment. 1996;p. 205–239
  15. Stavri GT, Hong Y, Zachary IC, et al.  Hypoxia and platelet-derived growth factor-BB synergistically upregulate the expression of vascular endothelial growth factor in vascular smooth muscle cells. FEBS Lett. 1995;358:311–315
  16. Namiki A, Brogi E, Kearney M, et al.  Hypoxia induces vascular endothelial growth factor in cultured human endothelial cells. J Biol Chem. 1995;270:31189–31195
  17. Waleh NS, Brody MD, Knapp MA, et al.  Mapping of the vascular endothelial growth factor-producing hypoxic cells in multicellular tumor spheroids using a hypoxia-specific marker. Cancer Res. 1995;55:6222–6226
  18. Mazure NM, Chen EY, Yeh P, et al.  Oncogenic tranformation an hypoxia synergistically act to modulate vascular endothelial growth factor expression. Cancer Res. 1996;56:3436–3440
  19. Chiarotto JA, Hill RP. A quantitative analysis of the reduction in oxygen levels required to induce up-regulation of vascular endothelial growth factor (VEGF) mRNA in cervical cancer cell lines. Br J Cancer. 1999;80:1518–1524
  20. Folkman J. Tumor angiogenesis. Adv Cancer Res. 1985;43:175–203
  21. Moses MA, Langer R. Inhibitors of angiogenesis. Biotech. 1991;9:630–634
  22. Schweigerer L. Antiangiogenesis as a novel therapeutic concept in pediatric oncology. J Mol Med. 1995;73:497–508
  23. Scott P, Harris AL. Current approaches to targeting cancer using antiangiogenesis therapies. Cancer Treat Rev. 1994;20:393–412
  24. Fan TP, Jaggar R, Bicknell R. Controlling the vasculature: Angiogenesis, anti-angiogenesis and vascular targeting of gene therapy. Trends Pharm Sci. 1995;16:57–66
  25. Kerbel RS. Tumor angiogenesis: Past, present and the near future. Carcinogenesis. 2000;21:505–515
  26. 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
  27. Kandel J, Bossy-Wetzel E, Radvanyi F, et al.  Neovascularization is associated with a switch to the export of bFGF in the multistep development of fibrosarcoma. Cell. 1991;66:1095–1104
  28. Benjamin LE, Golijanin D, Itin A, et al.  Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest. 1999;103:159–165
  29. Gorski DH, Beckett MA, Jaskowiak NT, et al.  Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res. 1999;59:3374–3378
  30. Strawn LM, McMahon G, App H, et al.  Flk-1 as a target for tumor growth inhibition. Cancer Res. 1996;56:3540–3545
  31. Witte L, Hicklin DJ, Zhu Z, et al.  Monoclonal antibodies targeting the VEGF receptor-2 (Flk1/KDR) as an anti-angiogenic therapeutic strategy. Cancer Metastasis Rev. 1998;17:155–161
  32. Klohs WD, Hamby JM. Antiangiogenic agents. Curr Opin Biotechnol. 1999;10:544–549
  33. Wedge SR, Ogilvie DJ, Dukes M, et al.  ZD4190: An orally active inhibitor of vascular endothelial growth factor signaling with broad-spectrum antitumor efficacy. Cancer Res. 2000;60:970–975
  34. Nguyen JT, Wu P, Clouse ME, et al.  Adeno-associated virus-mediated delivery of antiangiogenic factors as an antitumor strategy. Cancer Res. 1998;58:5673–5677
  35. Shi W, Siemann DW. Inhibition of renal cell carcinoma angiogenesis and growth by antisense oligonucleotides targeting vascular endothelial growth factor. Br J Cancer. 2002;87:119–126
  36. Zetter BR. Angiogenesis and tumor metastasis. Annu Rev Med. 1998;49:407–424
  37. O'Reilly MS, Holmgren L, Chen C, et al.  Angiostatin induces and sustains dormancy of human primary tumors in mice. Nat Med. 1996;2:689–692
  38. O'Reilly MS, Boehm T, Shing Y, et al.  Endostatin: An endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997;88:277–285
  39. Shi W, Teschendorf C, Muzyczka N, et al.  Adeno-associated virus-mediated gene transfer of endostatin inhibits angiogenesis and tumor growth in vivo. Cancer Gene Therapy. 2002;9:513–521
  40. Little RF, Wyvill KM, Pluda JM, et al.  Activity of thalidomide in AIDS-related Kaposi's sarcoma. J Clin Oncol. 2000;18:2593–2602
  41. Figg WD, Dahut W, Duray P, et al.  A randomized phase II trial of thalidomide, an angiogenesis inhibitor, in patients with androgen-independent prostate cancer. Clin Cancer Res. 2001;7:1888–1893
  42. Denekamp J. Vasculature as a target for tumour therapy. Prog Appl Microcirc. 1984;4:28–38
  43. Denekamp J. Angiogenesis, neovascular proliferation and vascular pathophysiology as targets for cancer therapy. Br J Radiol. 1993;66:181–196
  44. Cliffe S, Taylor ML, Rutland M, et al.  Combining bioreductive drugs (SR 4233 or SN 23862) with the vasoactive agents flavone acetic acid or 5,6-dimethylxanthenone acetic acid. Int J Radiat Oncol Biol Phys. 1994;29:373–377
  45. Rewcastle GW, Atwell GJ, Li ZA, et al.  Potential antitumor agents. 61. Structure-activity relationships for in vivo colon 38 activity among disubstituted 9-oxo-9H-xanthene-4-acetic acids. J Med Chem. 1991;34:217–222
  46. Ching LM, Joseph WR, Baguley BC. Antitumour responses to flavone-8-acetic acid and 5,6-dimethylxanthenone-4-acetic acid in immune deficient mice. Br J Cancer. 1992;66:128–130
  47. Laws AL, Matthew AM, Double JA, et al.  Preclinical in vitro and in vivo activity of 5,6-dimethylxanthenone-4-acetic acid. Br J Cancer. 1995;71:1204–1209
  48. Ching LM, Joseph WR, Crosier KE, et al.  Induction of tumor necrosis factor a messenger RNA in human and murine cells by the flavone acetic analogue 5,6, dimethylxanthenone-4-acetic acid (NSC64088). Cancer Res. 1994;54:870–872
  49. Philpott M, Baguley BC, Ching LM. Induction of tumour necrosis factor a by single and repeated doses of the antitumor agent 5,6-dimethylxanthenone-4-acetic acid. Cancer Chemother Pharmacol. 1995;36:143–148
  50. Zwi LJ, Baguley BC, Gavin JB, et al.  Necrosis in non-tumour tissues caused by flavone acetic acid and 5,6-dimethly xanthenone acetic acid. Brit J Cancer. 1990;62:932–934
  51. Wilson WR, Li AE, Cowan DS, et al.  Enhancement of tumor radiation response by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid. Int J Radiat Oncol Biol Phys. 1998;42:905–908
  52. Siemann DW, Mercer E, Lepler SE, et al.  Vascular targeting agents enhance chemotherapeutic agent activities in solid tumor therapy. Int J Cancer. 2002;99:1–6
  53. Dark GG, Hill SA, Prise VE, et al.  Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature. Cancer Res. 1997;57:1829–1834
  54. Grosios K, Holwell SE, McGown AT, et al.  In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug. Br J Cancer. 1999;81:1318–1327
  55. Li L, Rojiani A, Siemann DW. Targeting the tumor vasculature with combretastatin A-4 disodium phosphate: Effects on radiation therapy. Int J Radiat Oncol Biol Phys. 1998;42:899–903
  56. Rojiani AM, Li L, Rise L, et al.  Activity of the vascular targeting agent combretastatin A-4 disodium phosphate in a xenograft model of Aids-associated Kaposi's sarcoma. Acta Oncol. 2002;41:98–105
  57. Horsman MR, Ehrnrooth E, Ladekarl M, et al.  The effect of combretastatin A-4 disodium phosphate in a C3H mouse mammary carcinoma and a variety of murine spontaneous tumours. Int J Radiat Oncol Biol Phys. 1998;42:895–898
  58. Tozer GM, Prise VE, Wilson J, et al.  Combretastatin A-4 phosphate as a tumor vascular-targeting agent: Early effects in tumors and normal tissues. Cancer Res. 1999;59:1626–1634
  59. Hori K, Saito S, Nihei Y, et al.  Antitumor effects due to irreversible stoppage of tumor tissue blood flow: Evaluation of a novel combretastatin A-4 derivative, AC7700. Jpn J Cancer Res. 1999;90:1026–1038
  60. Blakey DC, Westwood FR, Walker M, et al.  Anti-tumor activity of the novel vascular targeting agent ZD6126 in a panel of tumor models. Clin Cancer Res. 2002;8:1974–1983
  61. Siemann DW, Rojiani AM. Enhancement of radiation therapy by the novel vascular targeting agent ZD6126. Int J Radiat Oncol Biol Phys. 2002;53:164–171
  62. Chaplin DJ, Pettit GR, Hill SA. Anti-vascular approaches to solid tumour therapy: Evaluation of combretastatin A4 phosphate. Anticancer Res. 1999;19:189–195
  63. Galbraith SM, Chaplin DJ, Lee F, et al.  Effects of combretastatin A4 phosphate on endothelial cell morphology in vitro and relationship to tumour vascular targeting activity in vivo. Anticancer Res. 2001;21:93–102
  64. 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
  65. Siemann DW, Warrington KH, Horsman MR. Targeting tumor blood vessels: An adjuvant strategy for radiation therapy. Radiother Oncol. 2000;57:5–12
  66. Steel GG, Peckham MJ. Exploitable mechanisms in combined radiotherapy-chemotherapy: The concept of additivity. Int J Radiat Oncol Biol Phys. 1979;5:85–91
  67. Teicher BA, Holden SA, Ara G, et al.  Potentiation of cytotoxic cancer therapies by TNP-470 alone and with other anti-angiogenic agents. Int J Cancer. 1994;57:920–925
  68. Lund EL, Bastholm L, Kristjansen PE. Therapeutic synergy of TNP-470 and ionizing radiation: effects on tumor growth, vessel morphology, and angiogenesis in human glioblastoma multiforme xenografts. Clin Cancer Res. 2000;6:971–978
  69. Lee CG, Heijn M, di Tomaso E, et al.  Anti-Vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions. Cancer Res. 2000;60:5565–5570
  70. Kozin SV, Boucher Y, Hicklin DJ, et al.  Vascular endothelial growth factor receptor-2-blocking antibody potentiates radiation-induced long-term control of human tumor xenografts. Cancer Res. 2001;61:39–44
  71. Ning S, Laird D, Cherrington JM, et al.  The antiangiogenic agents SU5416 and SU6668 increase the antitumor effects of fractionated irradiation. Radiat Res. 2002;157:45–51
  72. Hess C, Vuong V, Hegyi I, et al.  Effect of VEGF receptor inhibitor PTK787/ZK222584 [correction of ZK222548] combined with ionizing radiation on endothelial cells and tumour growth. Br J Cancer. 2001;85:2010–2016
  73. Geng L, Donnelly E, McMahon G, et al.  Inhibition of vascular endothelial growth factor receptor signaling leads to reversal of tumor resistance to radiotherapy. Cancer Res. 2001;61:2413–2419
  74. Gorski DH, Mauceri HJ, Salloum RM, et al.  Potentiation of the antitumor effect of ionizing radiation by brief concomitant exposures to angiostatin. Cancer Res. 1998;58:5686–5689
  75. Mauceri HJ, Hanna NN, Beckett MA, et al.  Combined effects of angiostatin and ionizing radiation in antitumour therapy. Nature. 1998;394:287–291
  76. Teicher BA, Holden SA, Dupuis NP, et al.  Potentiation of cytotoxic therapies by TNP-470 and minocycline in mice bearing EMT-6 mammary carcinoma. Breast Cancer Res Treat. 1995;36:227–236
  77. Teicher BA, Sotomayor EA, Huang ZD. Antiangiogenic agents potentiate cytotoxic cancer therapies against primary and metastatic disease. Cancer Res. 1992;52:6702–6704
  78. Dicker AP, William TL, Grant DS. Targeting angiogenic processes by combination rofecoxib and ionizing radiation. Am J Clin Oncol. 2001;24:438–442
  79. Kishi K, Petersen S, Petersen C, et al.  Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. Cancer Res. 2000;60:1326–1331
  80. Milas L, Mason K, Hunter N, et al.  In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. Clin Cancer Res. 2000;6:701–708
  81. Huang SM, Harari PM. Modulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas: Inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis. Clin Cancer Res. 2000;6:2166–2174
  82. Teicher BA, Depuis NP, Kusumoto T, et al.  Anti-angiogenic agents can increase tumor oxygenation and response to radiation therapy. Radiat Oncol Invest. 1995;269–276
  83. Harris AL, Fox S, Leek R, et al.  Breast cancer angiogenesis: Therapy target and prognostic factor. Eur J Cancer. 1995;31A:831–832
  84. Strohmeyer D. Pathophysiology of tumor angiogenesis and its relevance in renal cell cancer. Anticancer Res. 1999;19:1557–1561
  85. Hansen S, Grabau DA, Sorensen FB, et al.  The prognostic value of angiogenesis by Chalkley counting in a confirmatory study design on 836 breast cancer patients. Clin Cancer Res. 2000;6:139–146
  86. Sternfeld T, Foss HD, Kruschewski M, et al.  The prognostic significance of tumor vascularization in patients with localized colorectal cancer. Int J Colorectal Dis. 1999;14:272–276
  87. Wakisaka N, Wen QH, Yoshizaki T, et al.  Association of vascular endothelial growth factor expression with angiogenesis and lymph node metastasis in nasopharyngeal carcinoma. Laryngoscope. 1999;109:810–814
  88. Xiangming C, Hokita S, Natsugoe S, et al.  Angiogenesis as an unfavorable factor related to lymph node metastasis in early gastric cancer. Ann Surg Oncol. 1998;5:585–589
  89. Ohta Y, Watanabe Y, Murakami S, et al.  Vascular endothelial growth factor and lymph node metastasis in primary lung cancer. Br J Cancer. 1997;76:1041–1045
  90. Yoon SS, Eto H, Lin CM, et al.  Mouse endostatin inhibits the formation of lung and liver metastases. Cancer Res. 1999;59:6251–6256
  91. Zhu Z, Witte L. Inhibition of tumor growth and metastasis by targeting tumor-associated angiogenesis with antagonists to the receptors of vascular endothelial growth factor. Invest New Drugs. 1999;17:195–212
  92. Wylie S, MacDonald IC, Varghese HJ, et al.  The matrix metalloproteinase inhibitor batimastat inhibits angiogenesis in liver metastases of B16F1 melanoma cells. Clin Exp Metastasis. 1999;17:111–117
  93. Blezinger P, Wang J, Gondo M, et al.  Systemic inhibition of tumor growth and tumor metastases by intramuscular administration of the endostatin gene. Nat Biotechnol. 1999;17:343–348
  94. Cao Y, O'Reilly MS, Marshall B, et al.  Expression of angiostatin cDNA in a murine fibrosarcoma suppresses primary tumor growth and produces long-term dormancy of metastases. J Clin Invest. 1998;101:1055–1063
  95. Overgaard J, Horsman MR. Modification of hypoxia-induced radioresistance in tumors by the use of oxygen and sensitizers. Semin Radiat Oncol. 1996;6:10–21
  96. Walenta S, Schroeder T, Mueller-Klieser W. Metabolic mapping with bioluminescence: Basic and clinical relevance. Biomol Eng. 2002;18:249–262
  97. Lash CJ, Li AE, Rutland M, et al.  Enhancement of the anti-tumour effects of the antivascular agent 5,6-di-methylxanthenone-4-acetic acid (DMXAA) by combination with 5- hydroxytryptamine and bioreductive drugs. Br J Cancer. 1998;78:439–445
  98. Horsman MR, Murata R, Breidahl T, et al.  Combretastatins novel vascular targeting drugs for improving anti-cancer therapy. Combretastatins and conventional therapy. Adv Exp Med Biol. 2000;476:311–323
  99. Murata R, Overgaard J, Horsman MR. Combretastatin A-4 disodium phosphate: a vascular targeting agent that improves that improves the anti-tumor effects of hyperthermia, radiation, and mild thermoradiotherapy. Int J Radiat Oncol Biol Phys. 2001;51:1018–1024
  100. Murata R, Siemann DW, Overgaard J, et al.  Interaction between combretastatin A4 disodium phosphate and radiation in murine tumours. Radiother Oncol. 2001;60:155–161
  101. Murata R, Siemann DW, Overgaard J, et al.  Improved tumor response by combining radiation and the vascular damaging drug 5,6-dimethylxanthenone-4-acetic acid. Radiat Res. 2001;156:503–509
  102. Landuyt W, Ahmed B, Nuyts S, et al.  In vivo antitumor effect of vascular targeting combined with either ionizing radiation or anti-angiogenesis treatment. Int J Radiat Oncol Biol Phys. 2001;49:443–450
  103. Lozonschi L, Sunamura M, Kobari M, et al.  Controlling tumor angiogenesis and metastasis of C26 murine colon adenocarcinoma by a new matrix metalloproteinase inhibitor, KB-R7785, in two tumor models. Cancer Res. 1999;59:1252–1258
  104. O'Reilly MS, Holmgren L, Shing Y, et al.  Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell. 1994;79:315–328
  105. Wedge SR, Kendrew J, Ogilvie DJ, et al.  Combination of the VEGF receptor tyrosine kinase inhibitor ZD6474 and vascular-targeting agent ZD6126 produces an enhanced anti-tumor response. Proc Am Assoc Cancer Res. 2002;43:1081; (abstr)

 Supported by the U.S. National Cancer Institute (PHS grants CA84408 and CA89655).

☆☆ Dietmar W. Siemann serves as a consultant for AstraZeneca Pharmaceuticals and Oxigene Inc.

 Address reprint requests to Dietmar W. Siemann, PhD, Department of Radiation Oncology, University of Florida Shands Cancer Center, Box 100385, Gainesville, FL 32610.

PII: S1053-4296(03)50008-X

doi: 10.1053/srao.2003.50005

Seminars in Radiation Oncology
Volume 13, Issue 1 , Pages 53-61 , January 2003