Seminars in Oncology
Volume 33, Issue 5 , Pages 596-606 , October 2006

The Current Role of Angiogenesis Inhibitors in the Treatment of Renal Cell Carcinoma

References 

  1. Coppin C, Porzsolt F, Awa A, et al. Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev. 2005;CD001425
  2. Clifford SC, Maher ER. Von Hippel-Lindau disease: Clinical and molecular perspectives. Adv Cancer Res. 2001;82:85–105
  3. Gnarra JR, Lerman MI, Zbar B, et al. Genetics of renal-cell carcinoma and evidence for a critical role for von Hippel-Lindau in renal tumorigenesis. Semin Oncol. 1995;22:3–8
  4. Kondo K, Yao M, Yoshida M, et al. Comprehensive mutational analysis of the VHL gene in sporadic renal cell carcinoma: Relationship to clinicopathological parameters. Genes Chromosomes Cancer. 2002;34:58–68
  5. Gallou C, Joly D, Mejean A, et al. Mutations of the VHL gene in sporadic renal cell carcinoma: Definition of a risk factor for VHL patients to develop an RCC. Hum Mutat. 1999;13:464–475
  6. Schraml P, Struckmann K, Hatz F, et al. VHL mutations and their correlation with tumour cell proliferation, microvessel density, and patient prognosis in clear cell renal cell carcinoma. J Pathol. 2002;196:186–193
  7. Clifford SC, Prowse AH, Affara NA, et al. Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene and allelic losses at chromosome arm 3p in primary renal cell carcinoma: Evidence for a VHL-independent pathway in clear cell renal tumourigenesis. Genes Chromosomes Cancer. 1998;22:200–209
  8. Herman JG, Latif F, Weng Y, et al. Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci U S A. 1994;91:9700–9704
  9. Kibel A, Iliopoulos O, DeCaprio JA, et al. Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C. Science. 1995;269:1444–1446
  10. Krieg M, Haas R, Brauch H, et al. Up-regulation of hypoxia-inducible factors HIF-1alpha and HIF-2alpha under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function. Oncogene. 2000;19:5435–5443
  11. Gnarra JR, Zhou S, Merrill MJ, et al. Post-transcriptional regulation of vascular endothelial growth factor mRNA by the product of the VHL tumor suppressor gene. Proc Natl Acad Sci U S A. 1996;93:10589–10594
  12. Goodsell DS. The molecular perspective: VEGF and angiogenesis. Oncologist. 2002;7:569–570
  13. Kourembanas S, Hannan RL, Faller DV. Oxygen tension regulates the expression of the platelet-derived growth factor-B chain gene in human endothelial cells. J Clin Invest. 1990;86:670–674
  14. de Paulsen N, Brychzy A, Fournier MC, et al. Role of transforming growth factor-alpha in von Hippel–Lindau (VHL)(−/−) clear cell renal carcinoma cell proliferation: A possible mechanism coupling VHL tumor suppressor inactivation and tumorigenesis. Proc Natl Acad Sci U S A. 2001;98:1387–1392
  15. Kuwabara K, Ogawa S, Matsumoto M, et al. Hypoxia-mediated induction of acidic/basic fibroblast growth factor and platelet-derived growth factor in mononuclear phagocytes stimulates growth of hypoxic endothelial cells. Proc Natl Acad Sci U S A. 1995;92:4606–4610
  16. Grabmaier K, de Weijert MC, Verhaegh GW, et al. Strict regulation of CAIX(G250/MN) by HIF-1alpha in clear cell renal cell carcinoma. Oncogene. 2004;23:5624–5631
  17. Lee YS, Vortmeyer AO, Lubensky IA, et al. Coexpression of erythropoietin and erythropoietin receptor in von Hippel-Lindau disease-associated renal cysts and renal cell carcinoma. Clin Cancer Res. 2005;11:1059–1064
  18. Giordano FJ, Johnson RS. Angiogenesis: The role of the microenvironment in flipping the switch. Curr Opin Genet Dev. 2001;11:35–40
  19. Goodsell DS. The molecular perspective: VEGF and angiogenesis. Stem Cells. 2003;21:118–119
  20. Presta LG, Chen H, O’Connor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997;57:4593–4599
  21. Dagnaes-Hansen F, Rasmussen LM, Tilton R, et al. A murine vascular endothelial growth factor antibody inhibits in vivo growth of human Caki-I renal adenocarcinoma. Anticancer Res. 2003;23:1625–1630
  22. Margolin K, Gordon MS, Holmgren E, et al. 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. 2001;19:851–856
  23. Gordon MS, Margolin K, Talpaz M, et al. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol. 2001;19:843–850
  24. Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003;349:427–434
  25. Motzer RJ, Mazumdar M, Bacik J, et al. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol. 1999;17:2530–2540
  26. Yang JC. Bevacizumab for patients with metastatic renal cancer: An update. Clin Cancer Res. 2004;10:6367S-63S
  27. Elaraj DM, White DE, Steinberg SM, et al. A pilot study of antiangiogenic therapy with bevacizumab and thalidomide in patients with metastatic renal cell carcinoma. J Immunother. 2004;27:259–264
  28. Rini BI, Halabi S, Taylor J, et al. Cancer and Leukemia Group B 90206 A randomized phase III trial of interferon-alpha or interferon-alpha plus anti-vascular endothelial growth factor antibody (bevacizumab) in metastatic renal cell carcinoma. Clin Cancer Res. 2004;10:2584–2586
  29. Gabrilovich DI, Ishida T, Nadaf S, et al. Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. Clin Cancer Res. 1999;5:2963–2970
  30. Laxmanan S, Robertson SW, Wang E, et al. Vascular endothelial growth factor impairs the functional ability of dendritic cells through Id pathways. Biochem Biophys Res Commun. 2005;334:193–198
  31. Knebelmann B, Ananth S, Cohen HT, et al. Transforming growth factor alpha is a target for the von Hippel-Lindau tumor suppressor. Cancer Res. 1998;58:226–231
  32. Viloria-Petit A, Crombet T, Jothy S, et al. Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: A role for altered tumor angiogenesis. Cancer Res. 2001;61:5090–5101
  33. Hainsworth JD, Sosman JA, Spigel DR, et al. Treatment of metastatic renal cell carcinoma with a combination of bevacizumab and erlotinib. J Clin Oncol. 2005;23:7889–7896
  34. Data on file. South San Francisco, CA, Genentech Inc. Press release, October 18, 2005. http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=8967; accessed November 11, 2005
  35. Hainsworth JD, Sosman JA, Spigel DR, et al. Bevacizumab, erlotinib, and imatinib in the treatment of patients (pts) with advanced renal cell carcinoma (RCC): A Minnie Pearl Cancer Research Network phase I/II trial. Proc Am Soc Clin Oncol. 2005;23:16S;(abstr 4242)
  36. Holash J, Davis S, Papadopoulos N, et al. VEGF-Trap: A VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A. 2002;99:11393–11398
  37. Konner J, Dupont J. Use of soluble recombinant decoy receptor vascular endothelial growth factor trap (VEGF Trap) to inhibit vascular endothelial growth factor activity. Clin Colorectal Cancer. 2004;4(suppl 2):S81–S85
  38. Dupont J, Shwartz LL, Koutcher J, et al. Phase I and pharmacakinetic study of VEGF Trap administered subcutaneously (sc) to patients with advanced solid malignancies. Proc Am Soc Clin Oncol. 2004;23:16S;(abstr 3009)
  39. Dupont J, Rothenberg M, Spriggs DR, et al. Safety and pharmacokinetic of intravenous VEGF Trap in a phase I clinical trial of patients with advanced solid tumors. Proc Am Soc Clin Oncol. 2005;23:16S;(abstr 3029)
  40. Bergers G, Song S, Meyer-Morse N, et al. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest. 2003;111:1287–1295
  41. Sulzbacher I, Birner P, Traxler M, et al. Expression of platelet-derived growth factor-alpha receptor is associated with tumor progression in clear cell renal cell carcinoma. Am J Clin Pathol. 2003;120:107–112
  42. Heldin CH, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev. 1999;79:1283–1316
  43. Bhardwaj B, Klassen J, Cossette N, et al. Localization of platelet-derived growth factor beta receptor expression in the periepithelial stroma of human breast carcinoma. Clin Cancer Res. 1996;2:773–782
  44. Sundberg C, Branting M, Gerdin B, et al. Tumor cell and connective tissue cell interactions in human colorectal adenocarcinoma (Transfer of platelet-derived growth factor-AB/BB to stromal cells). Am J Pathol. 1997;151:479–492
  45. Xu L, Tong R, Cochran DM, et al. Blocking platelet-derived growth factor-D/platelet-derived growth factor receptor beta signaling inhibits human renal cell carcinoma progression in an orthotopic mouse model. Cancer Res. 2005;65:5711–5719
  46. Sun L, Tran N, Tang F, et al. Synthesis and biological evaluations of 3-substituted indolin-2-ones: A novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases. J Med Chem. 1998;41:2588–2603
  47. Mendel DB, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: Determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 2003;9:327–337
  48. Abrams TJ, Lee LB, Murray LJ, et al. SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther. 2003;2:471–478
  49. Murray LJ, Abrams TJ, Long KR, et al. SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. Clin Exp Metastasis. 2003;20:757–766
  50. Yee KW, Schittenhelm M, O’Farrell AM, et al. Synergistic effect of SU11248 with cytarabine or daunorubicin on FLT3 ITD-positive leukemic cells. Blood. 2004;104:4202–4209
  51. Marzola P, Degrassi A, Calderan L, et al. Early antiangiogenic activity of SU11248 evaluated in vivo by dynamic contrast-enhanced magnetic resonance imaging in an experimental model of colon carcinoma. Clin Cancer Res. 2005;11:5827–5832
  52. Demetri GD, Desai J, Fletcher JA, et al. 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. 2005;22:14S;(abstr 3001)
  53. Fiedler W, Serve H, Dohner H, et al. A phase 1 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. 2005;105:986–993
  54. Manning WC, Bello CL, Deprimo SE, et al. Pharmacokinetic and pharmacodynamic evaluation of SU11248 in a phase I clinical trial of patients with imatinib-resistant GIST. Proc Am Soc Clin Oncol. 2003;22:14S;(abstr 768)
  55. Rosen L, Mulay M, Long J, et al. Phase I trial of SU011248, a novel tyrosine kinase inhibitor in advanced solid tumors. Proc Am Soc Clin Oncol. 2003;22:14S;(abstr 765)
  56. Faivre S, Delbaldo C, Vera K, et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol. 2006;24:25–35
  57. Motzer R, Michaelson MD, Redman BG, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006;24:1–8
  58. Motzer RJ, Rini B, Bukowski RM, et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA. 2005;295:2516–2524
  59. DePrimo SE, Bello CL, Smeraglia J, et al. Soluble protein biomarkers of pharmacodynamic activity of the multi-targeted kinase inhibitor SU11248 in patients with metastatic renal cell cancer. Proc Am Assoc Cancer Res. 2005;46:(abstr 464)
  60. Beeram M, Patnaik A, Rowinsky EK. Raf: A strategic target for therapeutic development against cancer. J Clin Oncol. 2005;23:6771–6790
  61. Lee JT, McCubrey JA. Targeting the Raf kinase cascade in cancer therapy–novel molecular targets and therapeutic strategies. Exp Opin Ther Targets. 2002;6:659–678
  62. Bos JL. The ras gene family and human carcinogenesis. Mutat Res. 1988;195:255–271
  63. Dasgupta P, Sun J, Wang S, et al. Disruption of the Rb–Raf-1 interaction inhibits tumor growth and angiogenesis. Mol Cell Biol. 2004;24:9527–9541
  64. Oka H, Chatani Y, Hoshino R, et al. Constitutive activation of mitogen-activated protein (MAP) kinases in human renal cell carcinoma. Cancer Res. 1995;55:4182–4187
  65. Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64:7099–7109
  66. Wilhelm S, Chien DS. BAY 43-9006: Preclinical data. Curr Pharm Des. 2002;8:2255–2257
  67. Lyons JF, Wilhelm S, Hibner B, et al. Discovery of a novel Raf kinase inhibitor. Endocr Relat Cancer. 2001;8:219–225
  68. Awada A, Hendlisz A, Gil T, et al. Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer. 2005;92:1855–1861
  69. Clark JW, Eder JP, Ryan D, et al. Safety and pharmacokinetics of the dual action raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43-9006, in patients with advanced, refractory solid tumors. Clin Cancer Res. 2005;11:5472–5480
  70. Moore M, Hirte HW, Siu L, et al. Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol. 2005;16:1688–1694
  71. Strumberg D, Richly H, Hilger RA, et al. Phase I clinical and pharmacokinetic study of the novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol. 2005;23:965–972
  72. Ratain MJ, Eisen T, Stadler WM, et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib. J Clin Oncol. 2006;24:2505–2512
  73. Escudier BSC, Szczylik C, Eisen T, et al. Randomized phase III trial of the Raf kinase and VEGFR inhibitor sorafenib (BAY 43–9006) in patients with advanced renal cell carcinoma (RCC). Proc Am Soc Clin Oncol. 2005;23:16S;(abstr 4510)
  74. Inai T, Mancuso M, Hashizume H, et al. Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol. 2004;165:35–52
  75. Rugo HS, Herbst RS, Liu G, et al. Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: Pharmacokinetic and clinical results. J Clin Oncol. 2005;23:5474–5483
  76. Liu G, Rugo HS, Wilding G, et al. Dynamic contrast-enhanced magnetic resonance imaging as a pharmacodynamic measure of response after acute dosing of AG-013736, an oral angiogenesis inhibitor, in patients with advanced solid tumors: Results from a phase I study. J Clin Oncol. 2005;23:5464–5473
  77. Rini B, Rixe O, Bukowski RM, et al. AG-013736, a multi-target tyrosine kinase receptor inhibitor, demonstrates anti-tumor activity in a phase 2 study of cytokine-refractory, metastatic renal cell cancer (RCC). Proc Am Soc Clin Oncol. 2005;23:16S;(abstr 4509)
  78. Wood JM, Bold G, Buchdunger E, et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res. 2000;60:2178–2189
  79. Drevs J, Hofmann I, Hugenschmidt H, et al. Effects of PTK787/ZK 222584, a specific inhibitor of vascular endothelial growth factor receptor tyrosine kinases, on primary tumor, metastasis, vessel density, and blood flow in a murine renal cell carcinoma model. Cancer Res. 2000;60:4819–4824
  80. George D, Michaelson D, Oh WK, et al. Phase I study of PTK787/ZK 222584 (PTK/ZK) in metastatic renal cell carcinoma. Proc Am Soc Clin Oncol. 2003;22:385;(abstr 1548)
  81. Hecht JR, Trarbach T, Jaeger E, et al. A randomized, double-blind, placebo-controlled, phase III study in patients (Pts) with metastatic adenocarcinoma of the colon or rectum receiving first-line chemotherapy with oxaliplatin/5-fluorouracil/leucovorin and PTK787/ZK 222584 or placebo (CONFIRM-1). Proc Am Soc Clin Oncol. 2005;23:16S;(abstr 3)
  82. Kumar R, Harrington LE, Hopper TM, et al. Correlation of anti-tumor and anti-angiogenic activity of VEGFR inhibitors with inhibition of VEGFR2 phosphorylation in mice. Proc Am Soc Clin Oncol. 2005;23:16S;(abstr 9537)
  83. Hurwitz H, Dowlati A, Savage S, et al. Safety, tolerability and pharmacokinetics of oral administration of GW786034 in pts with solid tumors. Proc Am Soc Clin Oncol. 2005;23:16S;(abstr 3012)

PII: S0093-7754(06)00269-7

doi: 10.1053/j.seminoncol.2006.06.003

Seminars in Oncology
Volume 33, Issue 5 , Pages 596-606 , October 2006

Article Tools

* Image Usage & Resolution