Targeting angiogenesis for treatment of NSCLC brain metastases

Current Cancer Drug Targets

Volumn 12, Issue 3, 2012, Pages 289-299

  Schettino, C ^a   Bareschino, M A ^a   Rossi, A ^a   Maione, P ^a   Sacco, P C ^a   Colantuoni, G ^a   Rossi, E ^a   Gridelli, C ^a  

^a S G MOSCATI HOSPITAL   (Italy)

Author keywords

Angiogenesis; Bevacizumab; Brain metastases; Intracranial bleeding; NSCLC; Small molecules; VEGF

Indexed keywords

ANGIOGENESIS INHIBITOR; BETA CATENIN; BEVACIZUMAB; CARBOPLATIN; CEDIRANIB; CISPLATIN; ERLOTINIB; GEMCITABINE; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; LYMPHOID ENHANCER FACTOR 1; PACLITAXEL; PLATINUM; SUNITINIB; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN; VASCULOTROPIN RECEPTOR; VATALANIB; WNT PROTEIN;

ANTIANGIOGENIC THERAPY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ASTROCYTE; BLEEDING; BLOOD BRAIN BARRIER; BRAIN BLOOD VESSEL; BRAIN METASTASIS; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER SURVIVAL; CARCINOGENESIS; CELL INTERACTION; CENTRAL NERVOUS SYSTEM DISEASE; CYTOKINE RELEASE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG STRUCTURE; GLIA CELL; HISTOPATHOLOGY; HUMAN; INNATE IMMUNITY; LUNG NON SMALL CELL CANCER; MEDIATOR RELEASE; MEMBRANE TRANSPORT; MICROGLIA; MICROVASCULATURE; MOLECULAR WEIGHT; MULTICENTER STUDY (TOPIC); MULTIMODALITY CANCER THERAPY; NEOVASCULARIZATION (PATHOLOGY); NONHUMAN; OVERALL SURVIVAL; PATHOGENESIS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHASE 4 CLINICAL TRIAL (TOPIC); POST TREATMENT SURVIVAL; PROGRESSION FREE SURVIVAL; PROTEIN FUNCTION; PROTEIN INDUCTION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECEPTOR BLOCKING; REVIEW; STEREOTACTIC RADIOSURGERY; TREATMENT RESPONSE; TUMOR CELL DESTRUCTION; TUMOR NECROSIS;

EID: 84857127909     PISSN: 15680096     EISSN: 18735576     Source Type: Journal    
DOI: 10.2174/156800912799277476     Document Type: Review

References (81)

1. Jemal, A.; Siegel, R.; Ward, E.; Hao, Y.; Xu, J.; Thun, M. J. Cancer statistics, 2009. CA. Cancer J. Clin. 2009, 59, 225-249.
2. Mintz, A.; Perry, J.; Spithoff, K.; Chambers, A.; Lapierre, N. Management of single brain metastasis: A practice guideline. Curr. Oncol. 2007, 14, 131-143.
3. Eichler, A. F.; Loeffler, J. S. Multidisciplinary management of brain metastases. The Oncologist 2007, 12, 884-898.
4. Bradley, K. A.; Mehta, M. P. Management of brain metastases. Semin. Oncol. 2004, 31, 693-701.
5. Andrews, D. W.; Scott, C. B.; Sperduto, P. W.; Flanders, A. E.; Gaspar, L. E.; Schell, M. C.; Werner-Wasik, M.; Demas, W.; Ryu, J.; Bahary, J. P.; Souhami, L.; Rotman, M.; Mehta, M. P.; Curran, W. J. Jr. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: Phase III results of the RTOG 9508 randomised trial. Lancet 2004, 363, 1665-1672.
6. Oh, Y.; Stewart, D. J. Systemic therapy for lung cancer brain metastases: A rationale for clinical trials. Oncology 2008, 22, 168-178.
7. Aragon-Ching, J. B.; Zujewski, J. A. CNS metastasis: an old problem in a new guise. Clin. Cancer Res. 2007, 13, 1644-1647.
8. Ferrara, N.; Gerber, H. P.; LeCouter, J. The biology of VEGF and its receptors. Nat. Med. 2003, 9, 669-676.
9. Kamba, T.; McDonald, D. M. Mechanisms of adverse effects of anti VEGF therapy for cancer. Br. J. Cancer 2007, 96, 1788-1795.
10. Paget, S. The distribution of secondary growths in cancer of the breast. Lancet 1889, 1, 571-573.
11. th ed.; WB Saunders: Philadelphia, 1928.
12. Fidler, I. J. The pathogenesis of cancer metastasis: the'seed and soil'revisited. Nat. Rev. Cancer 2003, 3, 453-458.
13. Talmadge, J. E.; Fidler, I. J. AACR Centennial Series: the biology of cancer metastasis: historical perspective. Cancer Res. 2010, 70, 5649-5669.
14. Fidler, I. J.; Yano, S.; Zhang, R. D.; Fujimaki, T.; Bucana, C. D. The seed and soil hypothesis: vascularization and brain metastases. Lancet Oncol. 2002, 3, 53-57.
15. Hu, F.; Wang, R. Y.; Hsu, T. C. Clonal origin of metastasis in B16 murine melanoma: a cytogenetic study. J. Natl. Cancer Inst. 1987, 67, 947-956.
16. Langley, R. R.; Fidler, I. J. Tumor cell-organ microenvironment interactions in the pathogenesis of cancer metastasis. Endocr. Rev. 2007, 28, 297-321.
17. Mathieu, A.; Remmelink, M.; D'Haene, N.; Penant, S.; Gaussin, J. F.; Van Ginckel, R.; Darro, F.; Kiss, R.; Salmon, I. Development of a chemoresistant orthotopic human nonsmall cell lung carcinoma model in nude mice. Cancer 2004, 101, 1908-1918.
18. Carbonell, W.; Ansorge, O.; Sibson, N.; Muschel, R. The vascular basement membrane as soil in brain metastasis. PLoS ONE 2009, 4, e5857.
19. Zhang, Z.; Hatori, T.; Nonaka, H. An experimental model of brain metastasis of lung carcinoma. Neuropathology 2008, 28, 24-28.
20. Ohtsuki, S.; Terasaki, T. Contribution of carrier-mediated transport systems to the blood-brain barrier as a supporting and protecting interface for the brain; importance for CNS drug discovery and development. Pharm. Res. 2007, 24, 1745-1758.
21. Szakacs, G.; Paterson, J.; Ludwig, J.; Booth-Genthe, C.; Gottesman, M. Targeting multidrug resistance in cancer. Nature Rev. Drug Discov. 2006, 5, 219-234.
22. Noguchi, K.; Katayama, K.; Mitsuhashi, J.; Sugimoto, Y. Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. Adv. Drug Deliv. Rev. 2009, 61, 26-33.
23. Lockman, P. R.; Mittapalli, R. K.; Taskar, K. S.; Rudraraju, V.; Gril, B.; Bohn, K. A.; Adkins, C. E.; Roberts, A.; Thorsheim, H. R.; Gaasch, J. A.; Huang, S.; Palmieri, D.; Steeg, P. S.; Smith, Q. R. Heterogeneous blood-brain barrier permeability determines drug efficacy in mouse brain metastases of breast cancer. Clin. Cancer Res. 2010,16, 5662-5678.
24. Steward, P. A.; Hayakawa, K; Farrell, C. L.; Del Maestro, R. F. Quantitative study of microvessel ultrastructure in human peritumoral brain tissue. Evidence for a blood-brain barrier defect. J. Neurosurg. 1987, 67, 697-705.
25. Aloisi, F.; Ria, F.; Adorini, L. Regulation of T-cell responses by CNS antigen-presenting cells: different roles for microglia and astrocytes. Immunol. Today 2000, 21, 141-147.
26. Du, R.; Lu, K. V.; Petritsch, C; Liu, P.; Ganss, R.; Passegué, E.; Song, H.; Vandenberg, S.; Johnson, R. S.; Werb, Z.; Bergers, G. HIF1a induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell. 2008,13, 206-220.
27. Chen, L. W.; Yung, K. L.; Chan, Y. S. Reactive astrocytes as potential manipulation targets in novel cell replacement therapy of Parkinson's disease. Curr. Drug Targets 2005, 6, 821-833.
28. Seike, T.; Fujita, K; Yamakawa, Y.; Kido M. A.; Takiguchi, S.; Teramoto, N; Iguchi, H.; Mami Noda, M. Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis. Clin. Exp. Metastasis 2011, 28, 13-25.
29. Koo, J.; Kim, S. EGFR and HER-2 status of non-small cell lung cancer brain metastasis and corresponding primary tumor. Neoplasma 2011, 58, 27-34.
30. Wu, P. F.; Kuo, K. T.; Kuo, L. T.; Lin, Y. T.; Lee, W. C; Lu, Y. S.; Yang, C. H.; Wu, R. M.; Tu, Y. K; Tasi, J. C; Tseng, H. M.; Tseng, S. H.; Cheng, A. L.; Lin, C. H. O6-Methylguanine-DNA methyltransferase expression and prognostic value in brain metastases of lung cancers. Lung Cancer 2010, 68, 484-490.
31. Gomez-Roca, C; Raynaud, C. M.; Penault-Llorca, F.; Mercier, O.; Commo, F.; Morat, L.; Sabatier, L.; Dartevelle, P.; Taranchon, E.; Besse, B.; Validire, P.; Italiano, A.; Soria, J. C. Differential expression of biomarkers in primary non-small cell lung cancer and metastatic sites. J. Thorac. Oncol. 2009, 4, 1212-1220.
32. Nguyen, D. X.; Chiang, A. C; Zhang, X. H.; Kim, J. Y.; Kris, M. G; Ladanyi, M.; Gerald, W. L.; Massagué, J. WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis. Cell 2009,138, 51-62.
33. Xie, T. X.; Huang, F. J.; Aldape, K. D.; Kang, S. H.; Liu, M.; Gershenwald, J. E.; Xie, K; Sawaya, R.; Huang, S. Activation of stat3 in human melanoma promotes brain metastasis. Cancer Res. 2006, 66, 3188-3196.
34. Derycke, L. D.; Bracke, M. E. N-cadherin in the spotlight of cell-cell adhesion, differentiation, embryogenesis, invasion and signalling. Int. J. Dev. Biol. 2004, 48, 463-476.
35. Grinberg-Rashi, H.; Ofek, E.; Perelman, M.; Skarda, J.; Yaron, P.; Hajdúch, M.; Jacob-Hirsch, J.; Amariglio, N; Krupsky, M.; Simansky, DA.; Ram, Z.; Pfeffer, R.; Galernter, I.; Steinberg, D. M.; Ben-Dov, I.; Rechavi, G.; Izraeli, S. The expression of three genes in primary non-small cell lung cancer is associated with metastatic spread to the brain. Clin. Cancer Res. 2009, 15, 1755-1761.
36. Fidler, I. J.; Yano, S.; Zhang, R. D.; Fujimaki, T.; Bucana, C. D. 2002 The seed and soil hypothesis: vascularisation and brain metastases. Lancet Oncol. 2002, 3, 53-57.
37. Bergers, G.; Benjamin, L. E. Tumorigenesis and the angiogenic switch. Nat. Rev. Cancer 2003, 3, 401-410.
38. Hicklin, D. J.; Ellis, L. M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J. Clin. Oncol. 2005, 23, 1011-1027.
39. Kandel, J.; Bossy-Wtzel, E.; Radvanyi, F.; Klagsbrun, M.; Folkman, J.; Hanahan, D. Neovascularization is associated with a switch in the export of bFGF in the multistep development of fibrosarcoma. Cell 1991, 66, 1095-1104.
40. Risau, W. Mechanisms of angiogenesis. Nature 1997, 386, 671-674.
41. Ferrara, N; Gerber, H. P.; LeCouter, J. The biology of VEGF and its receptors. Nat. Med. 2003, 9, 669-676.
42. Houck, K; Ferrara, N; Winer, J.; Cachianes, G.; Li, B.; Leung, D. W. The vascular endothelial growth factor family: Identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol. Endocrinol. 1991, 5, 1806-1814.
43. Zachary, I.; Gliki, G. Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovasc. Res. 2001, 49, 568-581.
44. Eliceiri, B. P.; Cheresh, D. A. Adhesion events in angiogenesis. Curr. Opin. Cell Biol. 2001,13, 563-568.
45. Radisavljevic, Z.; Avraham, H.; Avraham, S. Vascular endothelial growth factor up-regulates ICAM-1 expression via the phosphatidylinositol 3 OH-kinase/AKT/nitric oxide pathway and modulates migration of brain microvascular endothelial cells. J. Biol. Chem. 2000, 275, 20770-20774.
46. Avraham, H. K; Lee, T. H.; Koh, Y.; Kim, T. A.; Jiang, S.; Sussman, M.; Samarel, A. M.; Avraham, S. Vascular endothelial growth factor regulates focal adhesion assembly in human brain microvascular endothelial cells through activation of the focal adhesion kinase and related adhesion focal tyrosine kinase. J. Biol. Chem. 2003, 278, 36661-36668.
47. Lee, T. H.; Seng, S.; Li, H.; Kennel, S. J.; Avraham, H. K; Avraham, S. Integrin regulation by vascular endothelial growth factor in human brain microvascular endothelial cells: role of afl integrin in angiogenesis. J. Biol. Chem. 2006, 281, 40450-40460.
48. Choong, P. F.; Nadesapillai, A. P. Urokinase plasminogen activator system: a multifunctional role in tumor progression and metastasis. Clin. Orthop. Relat. Res. 2003, (415 Suppl), S46-58.
49. Fanjul-Fernandez, M.; Folgueras, A. R.; Cabrera, S.; Lopez-Otin, C. Matrix metalloproteinases: Evolution, gene regulation and functional analysis in mouse models. Biochim. Biophys. Acta 2010, 1803, 3-19.
50. Page-McCaw, A.; Ewald, A. J.; Werb, Z. Matrix metalloproteinases and the regulation of tissue remodelling. Nat. Rev. Mol. Cell. Biol. 2007, 8, 221-233.
51. Kodate, M.; Kasai, T.; Hashimoto, H.; Yasumoto, K; Iwata, Y.; Manabe, H. Expression of matrix metalloproteinase (gelatinase) in T1 adenocarcinoma of the lung. Pathol. Int. 1997, 47, 461-469.
52. Schnaper, H. W.; Kleinman, H. K. Regulation of cell function by extracellular matrix. Pediatr. Nephrol. 1993, 7, 96-104.
53. Bergers, G.; Brekken, R.; McMahon, G.; Vu, T. H.; Itoh, T.; Tamaki, K; Tanzawa, K; Thorpe, P.; Itohara, S.; Werb, Z.; Hanahan, D. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat. Cell Biol. 2000, 2, 737-744.
54. Rojiani, M. V.; Alidina, J.; Esposito, N; Rojiani, A. M. Expression of MMP-2 correlates with increased angiogenesis in CNS metastasis of lung carcinoma. Int. J. Clin. Exp. Pathol. 2010, 3, 775-781.
55. Presta, L. G.; Chen, H.; O'Connor, S. J.; Chisholm, V.; Meng, Y. G; Krummen, L.; Winkler, M.; Ferrara, N. Humanization of an antivascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997, 57, 4593-4599.
56. Sandler, A.; Gray, R.; Perry, M. C; Brahmer, J.; Schiller, J. H.; Dowlati, A.; Lilenbaum, R.; Johnson, D. H. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N. Engl. J. Med. 2006, 355, 2542-2550.
57. Johnson, D. H.; Fehrenbacher, L.; Novotny, W. F.; Herbst, R. S.; Nemunaitis, J. J.; Jablons, D. M.; Langer, C. J.; De Vore, R. F.; Gaudreault, J.; Damico, L. A.; Holmgren, E.; Kabbinavar, F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J. Clin. Oncol. 2004,22, 2184-2191.
58. Reck, M.; von Pawel, J.; Zatloukal, P.; Ramlau, R.; Gorbounova, V.; Hirsh, V.; Leighl, N; Mezger, J.; Archer, V; Moore, N; Manegold, C. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J. Clin. Oncol. 2009, 27, 1227-1234.
59. Reck, M.; Von Pawel, J.; Zatloukal, P.; Ramlau, R.; Gorbounova, V.; Hirsh, V.; Leighl, N; Mezger, J.; Archer, V.; Moore, N; Manegold, C. BO17704 Study Group. Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann. Oncol. 2010, 21, 1804-1809.
60. Gordon, M. S.; Margolin, K; Talpaz, M.; Sledge, G.W.; Holmgren, E.; Benjamin, R.; Stalter, S.; Shak, S.; Adelman, D. 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.
61. Seinfeld, J.; Wagner, A. S.; Kleinschmidt-DeMasters, B. K. Brain metastases from hepatocellular carcinoma in US patients. J. Neurooncol. 2006, 76, 93-98.
62. Crinò, L.; Dansin, E.; Garrido, P.; Griesinger, F.; Laskin, J.; Pavlakis, N.; Stroiakovski, D.; Thatcher, N.; Tsai, C. M.; Wu, Y. L.; Zhou, C. Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study. Lancet Oncol. 2010, 11, 733-740.
63. Wozniak, A. J.; Garst, J.; Jahanzeb, M.; Kosty, M. P.; Vidaver, R.; Beatty, S.; Teng, S.; Flick, E. D.; Sing, A.; Lynch, T. J. Clinical outcomes (CO) for special populations of patients (pts) with advanced non-small cell lung cancer (NSCLC): Results from ARIES, a bevacizumab (BV) observational cohort study (OCS). J. Clin. Oncol. 2010, 28, 567s.
64. Socinski, M. A.; Langer, C. J.; Huang, J. E.; Kolb, M. M.; Compton, P.; Wang, L.; Akerley, W. Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. J. Clin. Oncol. 2009, 27, 5255-5261.
65. Miller, V. A.; O'Connor, P.; Soh, C.; Kabbinavar, F. A Randomized, double-blind, placebo-controlled, phase IIIb trial (ATLAS) comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy with B for first-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC). J. Clin. Oncol. 2009, 27, 407.
66. Kabbinavar, F. F.; Miller, V. A.; Johnson, B. E.; O'Connor, P. G.; Soh, C. Overall survival (OS) in ATLAS, a phase IIIb trial comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy (chemo) with B for first-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC). J. Clin. Oncol. 2010, 28, 544.
67. Akerley, W. L.; Langer, C. J.; Oh, Y.; Strickland, D. K.; Joo Royer, S.; Xia, Q.; Mu, Y.; Huang, J.; Socinski, M. A. Acceptable safety of bevacizumab therapy in patients with brain metastases due to non-small cell lung cancer. J. Clin. Oncol. 2008, 26, 403s.
68. Herbst, R. S.; Ansari, R.; Bustin, F.; Flynn, P. Hart, L.; Otterson, G. A.; Vlahovic, G.; Soh, C. H.; O'Connor, P.; Hainsworth, J. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet 2011, 377, 1846-1854.
69. De Braganca, K. C.; Janjigian, Y. Y.; Azzoli, C. G.; Kris, M. G.; Pietanza, M. C.; Nolan, C. P.; Omuro, A. M.; Holodny, A. I.; Lassman, A. B. Efficacy and safety of bevacizumab in active brain metastases from non-small cell lung cancer. J. Neurooncol. 2010, 100, 443-447.
70. Besse, B.; Lasserre, S. F.; Compton, P.; Huang, J.; Augustus, S.; Rohr, U. P. Bevacizumab Safety in Patients with Central Nervous System. Clin. Cancer Res. 2010, 16, 269-278.
71. Desjardins, A.; Reardon, D. A.; Herndon, J. E.; Marcello, J.; Quinn, J. A.; Rich, J. N.; Sathornsumetee, S.; Gururangan, S.; Sampson, J.; Bailey, L.; Bigner, D. D.; Friedman, A. H.; Friedman, H. S.; Vredenburgh, J. J. Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas. Clin. Cancer Res. 2008, 14, 7068-7073.
72. Lai, A.; Filka, E.; McGibbon, B.; Nghiemphu, P. L.; Graham, C.; Yong, W. H.; Mischel, P.; Liau, L. M.; Bergsneider, M.; Pope, W.; Selch, M.; Cloughesy, T. Phase II pilot study of bevacizumab in combination with temozolomide and regional radiation therapy for up-front treatment of patients with newly diagnosed glioblastoma multiforme: interim analysis of safety and tolerability. Int. J. Radiat. Oncol. Biol. Phys. 2008, 71, 1372-1380.
73. Abrams, T. J.; Lee, L. B.; Murray, L. J.; Pryer, N. K.; Cherrington J.M. 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.
74. Mendel, D. B.; Laird, A. D.; Xin, X.; Louie, S. G.; Christensen, J. G.; Li, G.; Schreck, R. E.; Abrams, T. J.; Ngai, T. J.; Lee, L. B.; Murray, L. J.; Carver, J.; Chan, E.; Moss, K. J.; Haznedar, J. O.; Sukbuntherng, J.; Blake, R. A.; Sun, L.; Tang, C.; Miller, T.; Shirazian, S.; McMahon, G.; Cherrington, J. M. 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/pharmacody-namic relationship. Clin. Cancer Res. 2003, 9, 327-337.
75. Socinski, M. A.; Novello, S.; Brahmer, J. R.; Rosell, R.; Sanchez, J. M.; Belani, C.; Govindan, R.; Atkin, J. N.; Gillenwater, H. H.; Pallares, C.; Tye, L.; Selaru, P.; Chao R. C.; Scagliotti, G. V. Multicenter, phase II trial of sunitinib in previously treated, advanced non-small-cell lung cancer. J. Clin. Oncol. 2008, 26, 650-656.
76. Novello, S.; Camps, C.; Grossi, F.; Mazieres, J.; Abrey, L.; Vernejoux, J. M.; Thall, A.; Patyna, S.; Usari, T.; Wang, Z.; Chao, R. C.; Scagliotti, G. Phase II study of sunitinib in patients with non-small cell lung cancer and irradiated brain metastases. J. Thorac. Oncol. 2011, 6, 1260-1266.
77. Patyna, S.; Peng, J. Distribution of sunitinib and its active metabolite in brain and spinal cord tissue following oral or intravenous administration in rodents and monkeys. Eur. J. Cancer 2006, 4, 21.
78. Wedge, S. R.; Kendrew, J.; Hennequin, L. F.; Valentine, P. J.; Barry, S. T.; Brave, S. R.; Smith, N. R.; James, N. H.; Dukes, M.; Curwen, J. O.; Chester, R.; Jackson, J. A.; Boffey, S. J.; Kilburn, L. L.; Barnett, S.; Richmond, G. H.; Wadsworth, P. F.; Walker, M.; Bigley, A. L.; Taylor, S. T.; Cooper L.; Beck, S.; Jürgensmeier, J. M.; Ogilvie, D. J. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005, 65, 4389-4400.
79. Williams, K. J.; Telfer, B. A.; Shannon, A. M.; Babur, M.; Stratford, I. J.; Wedge, S. R. Inhibition of vascular endothelial growth factor signalling using cediranib (RECENTIN; AZD2171) enhances radiation response and causes substantial physiological changes in lung tumour xenografts. Br. J. Radiol. 2008, 81, 21-27.
80. Gauler, T. C.; Besse, B.; Mauguen, A.; Meric, J. B.; Gounant, V.; Fischer, B.; Overbeck, T. R.; Krissel, H.; Laurent, D.; Tiainen, M.; Commo, F.; Soria, J. C.; Eberhardt, W. E. Phase II trial of PTK787/ZK 222584 (vatalanib) administered orally once-daily or in two divided daily doses as second-line monotherapy in relapsed or progressing patients with stage IIIB/IV non-small-cell lung cancer (NSCLC). Ann. Oncol. 2011 May 26. [Epub ahead of print].
81. Kim, L. S.; Huang, S.; Lu, W.; Lev, D. C.; Price, J. E. Vascular endothelial growth factor expression promotes the growth of breast cancer brain metastases in nude mice. Clin. Exp. Metastasis 2004, 21, 107-118.