Journal of Oncology
Volume 2010 (2010), Article ID 372547, 16 pages
doi:10.1155/2010/372547
Review Article

Antivascular Therapy for Epithelial Ovarian Cancer

Francois P. Duhoux1,2 and Jean-Pascal Machiels1

1Centre du Cancer, Department of Medical Oncology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, 1200 Brussels, Belgium
2F.R.S.-FNRS Research Fellow, Belgium

Received 27 May 2009; Accepted 28 September 2009

Academic Editor: Maurie M. Markman

Copyright © 2010 Francois P. Duhoux and Jean-Pascal Machiels. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. Jemal, R. Siegel, E. Ward, et al., “Cancer statistics, 2008,” CA: Cancer Journal for Clinicians, vol. 58, no. 2, pp. 71–96, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. L. Martin and R. Schilder, “Novel approaches in advancing the treatment of epithelial ovarian cancer: the role of angiogenesis inhibition,” Journal of Clinical Oncology, vol. 25, no. 20, pp. 2894–2901, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. J. Folkman, “Angiogenesis in cancer, vascular, rheumatoid and other disease,” Nature Medicine, vol. 1, no. 1, pp. 27–31, 1995. View at Scopus
  4. H. Yoshiji, S. Kuriyama, D. J. Hicklin, et al., “The vascular endothelial growth factor receptor KDR/Flk-1 is a major regulator of malignant ascites formation in the mouse hepatocellular carcinoma model,” Hepatology, vol. 33, no. 4, pp. 841–847, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. D. J. Hicklin and L. M. Ellis, “Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis,” Journal of Clinical Oncology, vol. 23, no. 5, pp. 1011–1027, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. N. Ferrara, H.-P. Gerber, and J. LeCouter, “The biology of VEGF and its receptors,” Nature Medicine, vol. 9, no. 6, pp. 669–676, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. X. B. Trinh, W. A. A. Tjalma, P. B. Vermeulen, et al., “The VEGF pathway and the AKT/mTOR/p70S6K1 signalling pathway in human epithelial ovarian cancer,” British Journal of Cancer, vol. 100, no. 6, pp. 971–978, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. A. Zhang, L. Meng, Q. Wang, et al., “Enhanced in vitro invasiveness of ovarian cancer cells through up-regulation of VEGF and induction of MMP-2,” Oncology Reports, vol. 15, no. 4, pp. 831–836, 2006. View at Scopus
  9. B. J. Monk, D. C. Choi, G. Pugmire, and R. A. Burger, “Activity of bevacizumab (rhuMAB VEGF) in advanced refractory epithelial ovarian cancer,” Gynecologic Oncology, vol. 96, no. 3, pp. 902–905, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. B. J. Monk, E. Han, C. A. Josephs-Cowan, G. Pugmire, and R. A. Burger, “Salvage bevacizumab (rhuMAB VEGF)-based therapy after multiple prior cytotoxic regimens in advanced refractory epithelial ovarian cancer,” Gynecologic Oncology, vol. 102, no. 2, pp. 140–144, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. R. A. Burger, M. W. Sill, B. J. Monk, B. E. Greer, and J. I. Sorosky, “Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group study,” Journal of Clinical Oncology, vol. 25, no. 33, pp. 5165–5171, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. S. A. Cannistra, U. A. Matulonis, R. T. Penson, et al., “Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer,” Journal of Clinical Oncology, vol. 25, no. 33, pp. 5180–5186, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. S. Mabuchi, Y. Terai, K. Morishige, et al., “Maintenance treatment with bevacizumab prolongs survival in an in vivo ovarian cancer model,” Clinical Cancer Research, vol. 14, no. 23, pp. 7781–7789, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. R. K. Jain, “Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy,” Science, vol. 307, no. 5706, pp. 58–62, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. P. J. Frederick, J. M. Straughn Jr., R. D. Alvarez, and D. J. Buchsbaum, “Preclinical studies and clinical utilization of monoclonal antibodies in epithelial ovarian cancer,” Gynecologic Oncology, vol. 113, no. 3, pp. 384–390, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. J. D. Wright, A. Hagemann, J. S. Rader, et al., “Bevacizumab combination therapy in recurrent, platinum-refractory, epithelial ovarian carcinoma: a retrospective analysis,” Cancer, vol. 107, no. 1, pp. 83–89, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. D. L. Richardson, F. J. Backes, L. G. Seamon, et al., “Combination gemcitabine, platinum, and bevacizumab for the treatment of recurrent ovarian cancer,” Gynecologic Oncology, vol. 111, no. 3, pp. 461–466, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. D. E. Cohn, S. Valmadre, K. E. Resnick, L. A. Eaton, L. J. Copeland, and J. M. Fowler, “Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer,” Gynecologic Oncology, vol. 102, no. 2, pp. 134–139, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. G. Bocci, G. Francia, S. Man, J. Lawler, and R. S. Kerbel, “Thrombospondin 1, a mediator of the antiangiogenic effects of low-dose metronomic chemotherapy,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 22, pp. 12917–12922, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. T. Browder, C. E. Butterfield, B. M. Kräling, et al., “Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer,” Cancer Research, vol. 60, no. 7, pp. 1878–1886, 2000. View at Scopus
  21. R. S. Kerbel and B. A. Kamen, “The anti-angiogenic basis of metronomic chemotherapy,” Nature Reviews Cancer, vol. 4, no. 6, pp. 423–436, 2004. View at Scopus
  22. J. C. Chura, K. Van Iseghem, L. S. Downs Jr., L. F. Carson, and P. L. Judson, “Bevacizumab plus cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer,” Gynecologic Oncology, vol. 107, no. 2, pp. 326–330, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  23. A. A. Garcia, H. Hirte, G. Fleming, et al., “Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia,” Journal of Clinical Oncology, vol. 26, no. 1, pp. 76–82, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. T. A. Yap, C. P. Carden, and S. B. Kaye, “Beyond chemotherapy: targeted therapies in ovarian cancer,” Nature Reviews Cancer, vol. 9, no. 3, pp. 167–181, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. J. M. S. Bartlett, S. P. Langdon, B. J. B. Simpson, et al., “The prognostic value of epidermal growth factor receptor mRNA expression in primary ovarian cancer,” British Journal of Cancer, vol. 73, no. 3, pp. 301–306, 1996. View at Scopus
  26. A. Psyrri, M. Kassar, Z. Yu, et al., “Effect of epidermal growth factor receptor expression level on survival in patients with epithelial ovarian cancer,” Clinical Cancer Research, vol. 11, no. 24, part 1, pp. 8637–8643, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. J. Tabernero, “The role of VEGF and EGFR inhibition: implications for combining anti-VEGF and anti-EGFR agents,” Molecular Cancer Research, vol. 5, no. 3, pp. 203–220, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. E. M. Posadas, M. S. Liel, V. Kwitkowski, et al., “A phase II and pharmacodynamic study of gefitinib in patients with refractory or recurrent epithelial ovarian cancer,” Cancer, vol. 109, no. 7, pp. 1323–1330, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. M. S. Gordon, D. Matei, C. Aghajanian, et al., “Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer: potential predictive relationship with tumor HER2 activation status,” Journal of Clinical Oncology, vol. 24, no. 26, pp. 4324–4332, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. H. S. Nimeiri, A. M. Oza, R. J. Morgan, et al., “Efficacy and safety of bevacizumab plus erlotinib for patients with recurrent ovarian, primary peritoneal, and fallopian tube cancer: a trial of the Chicago, PMH, and California Phase II consortia,” Gynecologic Oncology, vol. 110, no. 1, pp. 49–55, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. N. S. Azad, E. M. Posadas, V. E. Kwitkowski, et al., “Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity,” Journal of Clinical Oncology, vol. 26, no. 22, pp. 3709–3714, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. C. Treins, S. Giorgetti-Peraldi, J. Murdaca, G. L. Semenza, and E. Van Obberghen, “Insulin stimulates hypoxia-inducible factor 1 through a phosphatidylinositol 3-kinase/target of rapamycin-dependent signaling pathway,” Journal of Biological Chemistry, vol. 277, no. 31, pp. 27975–27981, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. H. Huynh, C. C. M. Teo, and K. C. Soo, “Bevacizumab and rapamycin inhibit tumor growth in peritoneal model of human ovarian cancer,” Molecular Cancer Therapeutics, vol. 6, no. 11, pp. 2959–2966, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. E. Van Cutsem, S. Berry, F. Rivera, et al., “Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study,” Annals of Oncology, vol. 20, no. 11, pp. 1842–1847, 2009. View at Publisher · View at Google Scholar · View at PubMed
  35. J. D. Wright, A. A. Secord, T. M. Numnum, et al., “A multi-institutional evaluation of factors predictive of toxicity and efficacy of bevacizumab for recurrent ovarian cancer,” International Journal of Gynecological Cancer, vol. 18, no. 3, pp. 400–406, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. F. Simpkins, J. L. Belinson, and P. G. Rose, “Avoiding bevacizumab related gastrointestinal toxicity for recurrent ovarian cancer by careful patient screening,” Gynecologic Oncology, vol. 107, no. 1, pp. 118–123, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. M. S. Gordon and D. Cunningham, “Managing patients treated with bevacizumab combination therapy,” Oncology, vol. 69, supplement 3, pp. 25–33, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. C. M. Burkart, J. J. Grisel, and D. B. Horn, “Spontaneous nasal septal perforation with antiangiogenic bevacizumab therapy,” Laryngoscope, vol. 118, no. 9, pp. 1539–1541, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. A. Jaishuen, J. P. Berrios-Rivera, N. Sirisabya, H. G. Zheng, Y. Li, and J. J. Kavanagh, “Erosive osteoarthritis during treatment with bevacizumab and paclitaxel in a patient with recurrent papillary serous carcinoma of the ovary,” International Journal of Gynecological Cancer, vol. 18, no. 2, pp. 379–383, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. A. T. Byrne, L. Ross, J. Holash, et al., “Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model,” Clinical Cancer Research, vol. 9, no. 15, pp. 5721–5728, 2003. View at Scopus
  41. L. Hu, J. Hofmann, J. Holash, G. D. Yancopoulos, A. K. Sood, and R. B. Jaffe, “Vascular endothelial growth factor trap combined with paclitaxel strikingly inhibits tumor and ascites, prolonging survival in a human ovarian cancer model,” Clinical Cancer Research, vol. 11, no. 19, part I, pp. 6966–6971, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. J. Dupont, M. L. Rothenberg, D. R. Spriggs, et al., “Safety and pharmacokinetics of intravenous VEGF Trap in a phase I clinical trial of patients with advanced solid tumors,” Journal of Clinical Oncology, vol. 23, no. 16S, p. 3029, 2005.
  43. ARD6122 or NCT00327171, “Study of AVE0005 (VEGF Trap) in Patients with Chemoresistant Advanced Ovarian Cancer,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00327171.
  44. ARD6772 or NCT00396591, “AVE0005 (VEGF Trap) in Patients with Recurrent Symptomatic Malignant Ascites,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00396591.
  45. W. P. Tew, N. Colombo, I. Ray-Coquard, et al., “VEGF-Trap for patients (pts) with recurrent platinum-resistant epithelial ovarian cancer (EOC): preliminary results of a randomized, multicenter phase II study,” Journal of Clinical Oncology, vol. 25, no. 18, supplement, p. 5508, 2007.
  46. NCT00436501, “VEGF Trap and Docetaxel in Treating Patients with Persistent or Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00436501.
  47. G. C. Jayson, C. Mulatero, M. Ranson, et al., “Phase I investigation of recombinant anti-human vascular endothelial growth factor antibody in patients with advanced cancer,” European Journal of Cancer, vol. 41, no. 4, pp. 555–563, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. U. A. Matulonis, S. T. Berlin, C. N. Krasner, et al., “Cediranib (AZD2171) is an active agent in recurrent epithelial ovarian cancer,” Journal of Clinical Oncology, vol. 26, no. 15, supplement, p. 5501, 2008.
  49. DFCI-05170 or NCT00275028, “AZD2171 in Treating Patients with Recurrent Ovarian, Peritoneal, or Fallopian Tube Cancer,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00275028.
  50. PMH-PHL-037 or NCT00278343, “AZD2171 in Treating Patients with Persistent, Recurrent, or Refractory Advanced Ovarian Epithelial, Peritoneal Cavity, or Fallopian Tube Cancer,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00278343.
  51. NCT00544973, “Carboplatin and Paclitaxel with or without Cediranib in Treating Women with Relapsed Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00544973.
  52. H.-Q. Miao, K. Hu, X. Jimenez, et al., “Potent neutralization of VEGF biological activities with a fully human antibody Fab fragment directed against VEGF receptor 2,” Biochemical and Biophysical Research Communications, vol. 345, no. 1, pp. 438–445, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. CP12-0711 or NCT00721162, “Study of IMC-1121B in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00721162.
  54. D. O. Holtz, R. T. Krafty, A. Mohamed-Hadley, et al., “Should tumor VEGF expression influence decisions on combining low-dose chemotherapy with antiangiogenic therapy? Preclinical modeling in ovarian cancer,” Journal of Translational Medicine, vol. 6, article 2, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  55. R. H. Alvarez, H. M. Kantarjian, and J. E. Cortes, “Biology of platelet-derived growth factor and its involvement in disease,” Mayo Clinic Proceedings, vol. 81, no. 9, pp. 1241–1257, 2006. View at Publisher · View at Google Scholar · View at Scopus
  56. A. Östman and C. Heldin, “PDGF receptors as targets in tumor treatment,” Advances in Cancer Research, vol. 97, pp. 247–274, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. R. Henriksen, K. Funa, E. Wilander, T. Bäckström, M. Ridderheim, and K. Oberg, “Expression and prognostic significance of platelet-derived growth factor and its receptors in epithelial ovarian neoplasms,” Cancer Research, vol. 53, no. 18, pp. 4550–4554, 1993. View at Scopus
  58. D. Matei, D. D. Chang, and M.-H. Jeng, “Imatinib mesylate (Gleevec) inhibits ovarian cancer cell growth through a mechanism dependent on platelet-derived growth factor receptor α and Akt inactivation,” Clinical Cancer Research, vol. 10, no. 2, pp. 681–690, 2004. View at Publisher · View at Google Scholar · View at Scopus
  59. D. Matei, S. Kelich, L. Cao, et al., “PDGF BB induces VEGF secretion in ovarian cancer,” Cancer Biology and Therapy, vol. 6, no. 12, pp. 1951–1959, 2007. View at Scopus
  60. R. L. Coleman, R. R. Broaddus, D. C. Bodurka, et al., “Phase II trial of imatinib mesylate in patients with recurrent platinum- and taxane-resistant epithelial ovarian and primary peritoneal cancers,” Gynecologic Oncology, vol. 101, no. 1, pp. 126–131, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. D. S. Alberts, P. Y. Liu, S. P. Wilczynski, et al., “Phase II trial of imatinib mesylate in recurrent, biomarker positive, ovarian cancer (Southwest Oncology Group Protocol S0211),” International Journal of Gynecological Cancer, vol. 17, no. 4, pp. 784–788, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  62. E. M. Posadas, V. Kwitkowski, H. L. Kotz, et al., “A prospective analysis of imatinib-induced c-KIT modulation in ovarian cancer: a phase II clinical study with proteomic profiling,” Cancer, vol. 110, no. 2, pp. 309–317, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  63. ID01-707 or NCT00510653, “Gleevec Study for Patients with Ovarian Cancer,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00510653.
  64. S. M. Apte, D. Fan, J. J. Killion, and I. J. Fidler, “Targeting the platelet-derived growth factor receptor in antivascular therapy for human ovarian carcinoma,” Clinical Cancer Research, vol. 10, no. 3, pp. 897–908, 2004. View at Publisher · View at Google Scholar · View at Scopus
  65. D. Matei, R. E. Emerson, J. Schilder, et al., “Imatinib mesylate in combination with docetaxel for the treatment of patients with advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis: a Hoosier Oncology Group trial,” Cancer, vol. 113, no. 4, pp. 723–732, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  66. NCT00840450, “Efficacy Study of Gleevec and Paclitaxel in Recurrent Patients of Ovarian and Other Cancers of Mullerian Origin,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00840450.
  67. C. Lu, P. H. Thaker, Y. G. Lin, et al., “Impact of vessel maturation on antiangiogenic therapy in ovarian cancer,” American Journal of Obstetrics and Gynecology, vol. 198, no. 4, pp. 477.e1–477.e10, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. J. A. Rauh-Hain and R. T. Penson, “Potential benefit of Sunitinib in recurrent and refractory ovarian clear cell adenocarcinoma,” International Journal of Gynecological Cancer, vol. 18, no. 5, pp. 934–936, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. R. J. Motzer, B. I. Rini, R. M. Bukowski, et al., “Sunitinib in patients with metastatic renal cell carcinoma,” Journal of the American Medical Association, vol. 295, no. 21, pp. 2516–2524, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  70. F. Torino, S. M. Corsello, R. Longo, A. Barnabei, and G. Gasparini, “Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy,” Nature Reviews Clinical Oncology, vol. 6, no. 4, pp. 219–228, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  71. A. Alavi, J. D. Hood, R. Frausto, D. G. Stupack, and D. A. Cheresh, “Role of Raf in vascular protection from distinct apoptotic stimuli,” Science, vol. 301, no. 5629, pp. 94–96, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  72. G. Singer, R. Oldt III, Y. Cohen, et al., “Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma,” Journal of the National Cancer Institute, vol. 95, no. 6, pp. 484–486, 2003. View at Scopus
  73. L. Dal Lago, V. D'Hondt, and A. Awada, “Selected combination therapy with sorafenib: a review of clinical data and perspectives in advanced solid tumors,” Oncologist, vol. 13, no. 8, pp. 845–858, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  74. H. DeGrendele, E. Chu, and J. Marshall, “Activity of the Raf kinase inhibitor BAY 43-9006 in patients with advanced solid tumors,” Clinical Colorectal Cancer, vol. 3, no. 1, pp. 16–18, 2003. View at Scopus
  75. L. Xu, J. Yoneda, C. Herrera, J. Wood, J. J. Killion, and I. J. Fidler, “Inhibition of malignant ascites and growth of human ovarian carcinoma by oral administration of a potent inhibitor of the vascular endothelial growth factor receptor tyrosine kinases,” International Journal of Oncology, vol. 16, no. 3, pp. 445–454, 2000.
  76. C. Li, M. Kuchimanchi, D. Hickman, et al., “In vitro metabolism of the novel, highly selective oral angiogenesis inhibitor motesanib diphosphate in preclinical species and in humans,” Drug Metabolism and Disposition, vol. 37, no. 7, pp. 1378–1394, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  77. F. Hilberg, G. J. Roth, M. Krssak, et al., “BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy,” Cancer Research, vol. 68, no. 12, pp. 4774–4782, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  78. J. A. Ledermann, G. J. Rustin, A. Hackshaw, et al., “A randomized phase II placebo-controlled trial using maintenance therapy to evaluate the vascular targeting agent BIBF 1120 following treatment of relapsed ovarian cancer (OC),” Journal of Clinical Oncology, vol. 27, no. 15, supplement, 2009, abstract no. 5501.
  79. A. Bagnato, F. Spinella, and L. Rosanò, “The endothelin axis in cancer: the promise and the challenges of molecularly targeted therapy,” Canadian Journal of Physiology and Pharmacology, vol. 86, no. 8, pp. 473–484, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  80. M. Smollich and P. Wülfing, “The endothelin axis: a novel target for pharmacotherapy of female malignancies,” Current Vascular Pharmacology, vol. 5, no. 3, pp. 239–248, 2007. View at Publisher · View at Google Scholar · View at Scopus
  81. A. Bagnato, D. Salani, V. Di Castro, et al., “Expression of endothelin 1 and endothelin A receptor in ovarian carcinoma: evidence for an autocrine role in tumor growth,” Cancer Research, vol. 59, no. 3, pp. 720–727, 1999. View at Scopus
  82. L. Rosanò, F. Spinella, D. Salani, et al., “Therapeutic targeting of the endothelin a receptor in human ovarian carcinoma,” Cancer Research, vol. 63, no. 10, pp. 2447–2453, 2003. View at Scopus
  83. S. Phuphanich, K. A. Carson, S. A. Grossman, et al., “Phase I safety study of escalating doses of atrasentan in adults with recurrent malignant glioma,” Neuro-Oncology, vol. 10, no. 4, pp. 617–623, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  84. J. W. Growcott, “Preclinical anticancer activity of the specific endothelin A receptor antagonist ZD4054,” Anti-Cancer Drugs, vol. 20, no. 2, pp. 83–88, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  85. L. Rosanò, V. Di Castro, F. Spinella, et al., “Combined targeting of endothelin A receptor and epidermal growth factor receptor in ovarian cancer shows enhanced antitumor activity,” Cancer Research, vol. 67, no. 13, pp. 6351–6359, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  86. L. Rosanò, V. Di Castro, F. Spinella, M. R. Nicotra, P. G. Natali, and A. Bagnato, “ZD4054, a specific antagonist of the endothelin A receptor, inhibits tumor growth and enhances paclitaxel activity in human ovarian carcinoma in vitro and in vivo,” Molecular Cancer Therapeutics, vol. 6, no. 7, pp. 2003–2011, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  87. R. T. Kurmasheva, F. C. Harwood, and P. J. Houghton, “Differential regulation of vascular endothelial growth factor by Akt and mammalian target of rapamycin inhibitors in cell lines derived from childhood solid tumors,” Molecular Cancer Therapeutics, vol. 6, no. 5, pp. 1620–1628, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  88. S. Mabuchi, D. A. Altomare, D. C. Connolly, et al., “RAD001 (Everolimus) delays tumor onset and progression in a transgenic mouse model of ovarian cancer,” Cancer Research, vol. 67, no. 6, pp. 2408–2413, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  89. S. Mabuchi, D. A. Altomare, M. Cheung, et al., “RAD001 inhibits human ovarian cancer cell proliferation, enhances cisplatin-induced apoptosis, and prolongs survival in an ovarian cancer model,” Clinical Cancer Research, vol. 13, no. 14, pp. 4261–4270, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  90. GOG-0186G or NCT00886691, “Bevacizumab with or without Everolimus in Treating Patients with Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00886691.
  91. R. Y. D. Fleming, L. M. Ellis, N. U. Parikh, W. Liu, C. A. Staley, and G. E. Gallick, “Regulation of vascular endothelial growth factor expression in human colon carcinoma cells by activity of src kinase,” Surgery, vol. 122, no. 2, pp. 501–507, 1997. View at Publisher · View at Google Scholar · View at Scopus
  92. J. M. Summy, J. G. Trevino, D. P. Lesslie, et al., “AP23846, a novel and highly potent Src family kinase inhibitor, reduces vascular endothelial growth factor and interleukin-8 expression in human solid tumor cell lines and abrogates downstream angiogenic processes,” Molecular Cancer Therapeutics, vol. 4, no. 12, pp. 1900–1911, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  93. J. G. Trevino, J. M. Summy, M. J. Gray, et al., “Expression and activity of Src regulate interleukin-8 expression in pancreatic adenocarcinoma cells: implications for angiogenesis,” Cancer Research, vol. 65, no. 16, pp. 7214–7222, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  94. D. Mukhopadhyay, L. Tsiokas, X.-M. Zhou, D. Foster, J. S. Brugge, and V. P. Sukhatme, “Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation,” Nature, vol. 375, no. 6532, pp. 577–581, 1995. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  95. L. Y. Han, C. N. Landen, J. G. Trevino, et al., “Antiangiogenic and antitumor effects of Src inhibition in ovarian carcinoma,” Cancer Research, vol. 66, no. 17, pp. 8633–8639, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  96. NCT00672295, “PH I SRC Kinase, Dasatinib Combo Paclitaxel & Carboplatin in Pts w Ovarian, Peritoneal, & Tubal Cancer,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00672295.
  97. NCI-09-C-0019 or NCT00792545, “Dasatinib and Bevacizumab in Treating Patients with Solid Tumors that are Metastatic or Cannot be Removed by Surgery,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00792545.
  98. OVERT-1 or NCT00610714, “AZD0530 Phase II Study in Patients with Advanced Ovarian Cancer (OVERT-1),” May 2009, http://clinicaltrials.gov/ct2/show/NCT00610714.
  99. C. N. Landen Jr., C. Lu, L. Y. Han, et al., “Efficacy and antivascular effects of EphA2 reduction with an agonistic antibody in ovarian cancer,” Journal of the National Cancer Institute, vol. 98, no. 21, pp. 1558–1570, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  100. Y. Yokoyama, G. Sedgewick, and S. Ramakrishnan, “Endostatin binding to ovarian cancer cells inhibits peritoneal attachment and dissemination,” Cancer Research, vol. 67, no. 22, pp. 10813–10822, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  101. NCT00004872, “Endostatin in Treating Patients with Advanced Refractory Solid Tumors,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00004872.
  102. NCT00004229, “Endostatin in Treating Patients with Advanced Solid Tumors,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00004229.
  103. I. B. Vergote, N. Colombo, E. Kutarska, et al., “Phase II study comparing volociximab (an antiangiogenic antibody) and pegylated liposomal doxorubicin (PLD) with PLD alone in recurrent ovarian or primary peritoneal cancer,” Journal of Clinical Oncology, vol. 27, no. 15, supplement, 2009, abstract no. 5560.
  104. R. J. D'Amato, M. S. Loughnan, E. Flynn, and J. Folkman, “Thalidomide is an inhibitor of angiogenesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 9, pp. 4082–4085, 1994. View at Scopus
  105. J. K. Chan, M. R. Manuel, G. Ciaravino, M. K. Cheung, A. Husain, and N. N. H. Teng, “Safety and efficacy of thalidomide in recurrent epithelial ovarian and peritoneal carcinoma,” Gynecologic Oncology, vol. 103, no. 3, pp. 919–923, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  106. M. E. Gordinier, D. S. Dizon, S. Weitzen, P. A. Disilvestro, R. G. Moore, and C. O. Granai, “Oral thalidomide as palliative chemotherapy in women with advanced ovarian cancer,” Journal of Palliative Medicine, vol. 10, no. 1, pp. 61–66, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  107. L. S. Downs Jr., P. L. Judson, P. A. Argenta, et al., “A prospective randomized trial of thalidomide with topotecan compared with topotecan alone in women with recurrent epithelial ovarian carcinoma,” Cancer, vol. 112, no. 2, pp. 331–339, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  108. NCT00004876, “Carboplatin with or without Thalidomide in Treating Patients with Ovarian Epithelial Cancer,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00004876.
  109. M. Tsujii, S. Kawano, S. Tsuji, H. Sawaoka, M. Hori, and R. N. DuBois, “Cyclooxygenase regulates angiogenesis induced by colon cancer cells,” Cell, vol. 93, no. 5, pp. 705–716, 1998. View at Publisher · View at Google Scholar · View at Scopus
  110. Y. Yokoyama, B. Xin, T. Shigeto, et al., “Clofibric acid, a peroxisome proliferator-activated receptor α ligand, inhibits growth of human ovarian cancer,” Molecular Cancer Therapeutics, vol. 6, no. 4, pp. 1379–1386, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  111. B. Xin, Y. Yokoyama, T. Shigeto, M. Futagami, and H. Mizunuma, “Inhibitory effect of meloxicam, a selective cyclooxygenase-2 inhibitor, and ciglitazone, a peroxisome proliferator-activated receptor gamma ligand, on the growth of human ovarian cancers,” Cancer, vol. 110, no. 4, pp. 791–800, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  112. NCT00084448, “Paclitaxel and Celecoxib in Treating Patients with Recurrent or Persistent Platinum-Resistant Ovarian Epithelial or Primary Peritoneal Cancer,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00084448.
  113. NCT00538031, “Cyclophosphamide with or without Celecoxib in Treating Patients with Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00538031.
  114. Y. Takei, Y. Saga, H. Mizukami, et al., “Overexpression of PTEN in ovarian cancer cells suppresses i.p. dissemination and extends survival in mice,” Molecular Cancer Therapeutics, vol. 7, no. 3, pp. 704–711, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  115. W. M. Merritt, Y. G. Lin, W. A. Spannuth, et al., “Effect of interleukin-8 gene silencing with liposome-encapsulated small interfering RNA on ovarian cancer cell growth,” Journal of the National Cancer Institute, vol. 100, no. 5, pp. 359–372, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  116. D. E. Weng, P. A. Masci, S. F. Radka, et al., “A phase I clinical trial of a ribozyme-based angiogenesis inhibitor targeting vascular endothelial growth factor receptor-1 for patients with refractory solid tumors,” Molecular Cancer Therapeutics, vol. 4, no. 6, pp. 948–955, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  117. NCT00021021, “RPI.4610 in Treating Patients with Metastatic Kidney Cancer,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00021021.
  118. F. Wei, S. Cao, X. Ren, et al., “Efficient antiproliferative and antiangiogenic effects on human ovarian cancer growth by gene transfer of attenuated mutants of Shiga-like toxin I,” International Journal of Gynecological Cancer, vol. 18, no. 4, pp. 677–691, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  119. P. Bhargava, J. L. Marshall, W. Dahut, et al., “A Phase I and pharmacokinetic study of squalamine, a novel antiangiogenic agent, in patients with advanced cancers,” Clinical Cancer Research, vol. 7, no. 12, pp. 3912–3919, 2001. View at Scopus
  120. NCT00021385, “Squalamine Lactate Plus Carboplatin in Treating Patients with Recurrent or Refractory Stage III or Stage IV Ovarian Cancer,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00021385.
  121. M. M. Hussain, H. Kotz, L. Minasian, et al., “Phase II trial of carboxyamidotriazole in patients with relapsed epithelial ovarian cancer,” Journal of Clinical Oncology, vol. 21, no. 23, pp. 4356–4363, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  122. C. R. Tait and P. F. Jones, “Angiopoietins in tumours: the angiogenic switch,” Journal of Pathology, vol. 204, no. 1, pp. 1–10, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  123. NCT00770536, “A Phase 1b Study of AMG 386 in Combination with Either Pegylated Liposomal Doxorubicin or Topotecan in Subjects with Advanced Recurrent Epithelial Ovarian Cancer,” May 2009, http://clinicaltrials.gov/ct2/show/NCT00770536.
  124. D. Fukumura and R. K. Jain, “Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize,” Journal of Cellular Biochemistry, vol. 101, no. 4, pp. 937–949, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  125. G. M. Tozer, C. Kanthou, and B. C. Baguley, “Disrupting tumour blood vessels,” Nature Reviews Cancer, vol. 5, no. 6, pp. 423–435, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  126. P. Hinnen and F. A. L. M. Eskens, “Vascular disrupting agents in clinical development,” British Journal of Cancer, vol. 96, no. 8, pp. 1159–1165, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  127. P. D. Davis, G. J. Dougherty, D. C. Blakey, et al., “ZD6126: a novel vascular-targeting agent that causes selective destruction of tumor vasculature,” Cancer Research, vol. 62, no. 24, pp. 7247–7253, 2002. View at Scopus
  128. T. J. Kim, M. Ravoori, C. N. Landen, et al., “Antitumor and antivascular effects of AVE8062 in ovarian carcinoma,” Cancer Research, vol. 67, no. 19, pp. 9337–9345, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  129. D. W. Siemann, E. Mercer, S. Lepler, and A. M. Rojiani, “Vascular targeting agents enhance chemotherapeutic agent activities in solid tumor therapy,” International Journal of Cancer, vol. 99, no. 1, pp. 1–6, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  130. F. Pastorino, C. Brignole, D. Marimpietri, et al., “Vascular damage and anti-angiogenic effects of tumor vessel-targeted liposomal chemotherapy,” Cancer Research, vol. 63, no. 21, pp. 7400–7409, 2003. View at Scopus
  131. F. Pastorino, D. Di Paolo, F. Piccardi, et al., “Enhanced antitumor efficacy of clinical-grade vasculature-targeted liposomal doxorubicin,” Clinical Cancer Research, vol. 14, no. 22, pp. 7320–7329, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  132. R. C. Bast Jr., F.-J. Xu, Y.-H. Yu, S. Barnhill, Z. Zhang, and G. B. Mills, “CA 125: the past and the future,” International Journal of Biological Markers, vol. 13, no. 4, pp. 179–187, 1998. View at Scopus
  133. B. W. T. Yin, A. Dnistrian, and K. O. Lloyd, “Ovarian cancer antigen CA125 is encoded by the MUC16 mucin gene,” International Journal of Cancer, vol. 98, no. 5, pp. 737–740, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  134. N. S. Azad, C. M. Annunziata, S. M. Steinberg, et al., “Lack of reliability of CA125 response criteria with anti-VEGF molecularly targeted therapy,” Cancer, vol. 112, no. 8, pp. 1726–1732, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  135. E. A. Eisenhauer, P. Therasse, J. Bogaerts, et al., “New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1),” European Journal of Cancer, vol. 45, no. 2, pp. 228–247, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  136. A. Sabir, R. Schor-Bardach, C. J. Wilcox, et al., “Perfusion MDCT enables early detection of therapeutic response to antiangiogenic therapy,” American Journal of Roentgenology, vol. 191, no. 1, pp. 133–139, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  137. H. C. Hollingsworth, E. C. Kohn, S. M. Steinberg, M. L. Rothenberg, and M. J. Merino, “Tumor angiogenesis in advanced stage ovarian carcinoma,” American Journal of Pathology, vol. 147, no. 1, pp. 33–41, 1995. View at Scopus
  138. J. E. Palmer, L. J. Sant Cassia, C. J. Irwin, A. G. Morris, and T. P. Rollason, “Prognostic value of measurements of angiogenesis in serous carcinoma of the ovary,” International Journal of Gynecological Pathology, vol. 26, no. 4, pp. 395–403, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  139. K. A. Suhonen, M. A. Anttila, S. M. Sillanpää, et al., “Quantification of angiogenesis by the Chalkley method and its prognostic significance in epithelial ovarian cancer,” European Journal of Cancer, vol. 43, no. 8, pp. 1300–1307, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  140. G. H. Shen, M. Ghazizadeh, O. Kawanami, et al., “Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma,” British Journal of Cancer, vol. 83, no. 2, pp. 196–203, 2000. View at Scopus
  141. S. A. O'Toole, B. L. Sheppard, A. Laios, et al., “Potential predictors of chemotherapy response in ovarian cancer—how do we define chemosensitivity?” Gynecologic Oncology, vol. 104, no. 2, pp. 345–351, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  142. M. R. Raspollini, G. Amunni, A. Villanucci, G. Baroni, V. Boddi, and G. L. Taddei, “Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma,” International Journal of Gynecological Cancer, vol. 14, no. 5, pp. 815–823, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  143. T. J. Duncan, A. Al-Attar, P. Rolland, et al., “Vascular endothelial growth factor expression in ovarian cancer: a model for targeted use of novel therapies?” Clinical Cancer Research, vol. 14, no. 10, pp. 3030–3035, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  144. C. Tempfer, A. Obermair, L. Hefler, G. Haeusler, G. Gitsch, and C. Kainz, “Vascular endothelial growth factor serum concentrations in ovarian cancer,” Obstetrics and Gynecology, vol. 92, no. 3, pp. 360–363, 1998. View at Publisher · View at Google Scholar · View at Scopus
  145. L. A. Hefler, A. Mustea, D. Könsgen, et al., “Vascular endothelial growth factor gene polymorphisms are associated with prognosis in ovarian cancer,” Clinical Cancer Research, vol. 13, no. 3, pp. 898–901, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  146. M. Mendiola, J. Barriuso, A. Redondo, et al., “Angiogenesis-related gene expression profile with independent prognostic value in advanced ovarian carcinoma,” PLoS ONE, vol. 3, no. 12, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  147. R. J. Buckanovich, D. Sasaroli, A. O'Brien-Jenkins, et al., “Tumor vascular proteins as biomarkers in ovarian cancer,” Journal of Clinical Oncology, vol. 25, no. 7, pp. 852–861, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  148. R. M. Strieter, M. D. Burdick, J. Mestas, B. Gomperts, M. P. Keane, and J. A. Belperio, “Cancer CXC chemokine networks and tumour angiogenesis,” European Journal of Cancer, vol. 42, no. 6, pp. 768–778, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  149. Y. Mizukami, W.-S. Jo, E.-M. Duerr, et al., “Induction of interleukin-8 preserves the angiogenic response in HIF-1α-deficient colon cancer cells,” Nature Medicine, vol. 11, no. 9, pp. 992–997, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  150. A. M. Schultheis, G. Lurje, K. E. Rhodes, et al., “Polymorphisms and clinical outcome in recurrent ovarian cancer treated with cyclophosphamide and bevacizumab,” Clinical Cancer Research, vol. 14, no. 22, pp. 7554–7563, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  151. T. J. Shaw and B. C. Vanderhyden, “AKT mediates the pro-survival effects of KIT in ovarian cancer cells and is a determinant of sensitivity to imatinib mesylate,” Gynecologic Oncology, vol. 105, no. 1, pp. 122–131, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  152. J. L. Alcázar, “Tumor angiogenesis assessed by three-dimensional power Doppler ultrasound in early, advanced and metastatic ovarian cancer: a preliminary study,” Ultrasound in Obstetrics and Gynecology, vol. 28, no. 3, pp. 325–329, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  153. I. Thomassin-Naggara, M. Bazot, E. Daraï, P. Callard, J. Thomassin, and C. A. Cuenod, “Epithelial ovarian tumors: value of dynamic contrast-enhanced MR imaging and correlation with tumor angiogenesis,” Radiology, vol. 248, no. 1, pp. 148–159, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  154. W. B. Nagengast, E. G. de Vries, G. A. Hospers, et al., “In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft,” Journal of Nuclear Medicine, vol. 48, no. 8, pp. 1313–1319, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  155. H. Wang, W. Cai, K. Chen, et al., “A new PET tracer specific for vascular endothelial growth factor receptor 2,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 34, no. 12, pp. 2001–2010, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus