Anti-angiogenic drugs and biomarkers in non-small-cell lung cancer: A 'hard days night'

Current Pharmaceutical Design

Volumn 20, Issue 24, 2014, Pages 3958-3972

  Pilotto, Sara ^a   Bonomi, Maria ^a   Massari, Francesco ^a   Milella, Michele ^b   Ciuffreda, Ludovica ^b   Brunelli, Matteo ^a   Fassan, Matteo ^a   Chilosi, Marco ^a   Scarpa, Aldo ^a   Tortora, Giampaolo ^a   Bria, Emilio ^a  

^a UNIVERSITY HOSPITAL OF VERONA   (Italy)

^b REGINA ELENA NATIONAL CANCER INSTITUTE   (Italy)

Author keywords

Angiogenesis; Lung cancer; Review

Indexed keywords

AFLIBERCEPT; ANGIOGENESIS INHIBITOR; BEVACIZUMAB; FIBROBLAST GROWTH FACTOR; FIBROBLAST GROWTH FACTOR RECEPTOR 2; INTERLEUKIN 17; INTERLEUKIN 8; MICRORNA; MICRORNA 155; MICRORNA 17 92; MICRORNA 21; MICRORNA 221; MICRORNA 29; MOTESANIB; PLATELET DERIVED GROWTH FACTOR A; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; PLATELET DERIVED GROWTH FACTOR B; PLATELET DERIVED GROWTH FACTOR C; PROSTAGLANDIN E2; PROSTAGLANDIN SYNTHASE; SORAFENIB; SUNITINIB; TUMOR MARKER; UNCLASSIFIED DRUG; UNINDEXED DRUG; VADIMEZAN; VANDETANIB; VASCULOTROPIN; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 3; ANTINEOPLASTIC AGENT;

ALTERNATIVE RNA SPLICING; ANGIOGENESIS; ANTIANGIOGENIC THERAPY; ARTICLE; CANCER CHEMOTHERAPY; CANCER PROGNOSIS; CANCER RECURRENCE; CANCER SURVIVAL; CAPILLARY DENSITY; DISEASE SPECIFIC SURVIVAL; DRUG EFFICACY; GENE OVEREXPRESSION; HUMAN; LUNG NON SMALL CELL CANCER; LYMPH NODE METASTASIS; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; SINGLE NUCLEOTIDE POLYMORPHISM; SURVIVAL PREDICTION; TREATMENT RESPONSE; ANTAGONISTS AND INHIBITORS; CARCINOMA, NON-SMALL-CELL LUNG; GENETICS; LUNG NEOPLASMS; METABOLISM; NEOVASCULARIZATION, PATHOLOGIC;

ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARCINOMA, NON-SMALL-CELL LUNG; HUMANS; LUNG NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; TUMOR MARKERS, BIOLOGICAL;

EID: 84903973557     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/13816128113196660757     Document Type: Article

References (182)

1. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285: 1182-1186.
2. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57-70.
3. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 144: 646-674.
4. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996; 86: 353-364.
5. Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer 2003; 3: 401-410.
6. Baeriswyl V, Christofori G. The angiogenic switch in carcinogenesis. Semin Cancer Biol 2009; 19: 329-337.
7. Nagy JA, Chang SH, Shih SC, et al. Heterogeneity of the tumor vasculature. Semin Thromb Hemost 36: 321-331.
8. Raica M, Cimpean AM, Ribatti D. Angiogenesis in pre-malignant conditions. Eur J Cancer 2009; 45: 1924-1934.
9. Ferrara N. Vascular endothelial growth factor. Arterioscler Thromb Vasc Biol 2009; 29: 789-791.
10. Mac Gabhann F, Popel AS. Systems biology of vascular endothe-lial growth factors. Microcirculation 2008; 15: 715-738.
11. Kazerounian S, Yee KO, Lawler J. Thrombospondins in cancer. Cell Mol Life Sci 2008; 65: 700-712.
12. Lieu C, Heymach J, Overman M, et al. Beyond VEGF: inhibition of the fibroblast growth factor pathway and antiangiogenesis. Clin Cancer Res 17: 6130-6139.
13. Kono SA, Heasley LE, Doebele RC, Camidge DR. Adding to the Mix: Fibroblast Growth Factor and Platelet-derived Growth Factor Receptor Pathways as Targets in Non-small Cell Lung Cancer. Curr Cancer Drug Targets.
14. Ribatti D. Endogenous inhibitors of angiogenesis: a historical review. Leuk Res 2009; 33: 638-644.
15. Raza A, Franklin MJ, Dudek AZ. Pericytes and vessel maturation during tumor angiogenesis and metastasis. Am J Hematol 85: 593-598.
16. Zumsteg A, Christofori G. Corrupt policemen: inflammatory cells promote tumor angiogenesis. Curr Opin Oncol 2009; 21: 60-70.
17. Huang Y, Goel S, Duda DG, et al. Vascular normalization as an emerging strategy to enhance cancer immunotherapy. Cancer Res 2012; 73: 2943-2948.
18. Fan F, Schimming A, Jaeger D, Podar K. Targeting the tumor microenvironment: focus on angiogenesis. J Oncol 2012: 281261.
19. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006; 355: 2542-2550.
20. Reck M, von Pawel J, Zatloukal P, et al. 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.
21. Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 2007; 370: 2103-2111.
22. Saltz LB, Clarke S, Diaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008; 26: 2013-2019.
23. Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOL-FOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007; 25: 1539-1544.
24. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335-2342.
25. Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007; 357: 2666-2676.
26. Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2009; 27: 4733-4740.
27. Kreisl TN, Kim L, Moore K, et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 2009; 27: 740-745.
28. Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevaci-zumab in ovarian cancer. N Engl J Med 365: 2484-2496.
29. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007; 356: 125-134.
30. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus inter-feron alfa in metastatic renal-cell carcinoma. N Engl J Med 2007; 356: 115-124.
31. Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28: 1061-1068.
32. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 378: 1931-1939.
33. Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stro-mal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006; 368: 1329-1338.
34. Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 364: 501-513.
35. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378-390.
36. van der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for me-tastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2012; 379: 1879-1886.
37. Van Cutsem E, Tabernero J, Lakomy R, et al. Addition of afliber-cept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 2012; 30: 3499-3506.
38. Bokemeyer C, Bondarenko I, Makhson A, et al. Fluorouracil, leu-covorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 2009; 27: 663-671.
39. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008; 359: 1116-1127.
40. Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009; 360: 1408-1417.
41. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010; 376: 687-697.
42. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344: 783-792.
43. Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metas-tatic colorectal cancer. J Clin Oncol 2007; 25: 1658-1664.
44. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacar-bazine for previously untreated metastatic melanoma. N Engl J Med 2011; 364: 2517-2526.
45. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363: 711-723.
46. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947-957.
47. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005; 353: 123-132.
48. Cappuzzo F, Ciuleanu T, Stelmakh L, et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multi-centre, randomised, placebo-controlled phase 3 study. Lancet Oncol 11: 521-529.
49. Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007; 25: 1960-1966.
50. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer. N Engl J Med 2013.
51. Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008; 372: 449-456.
52. Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 2011; 364: 514-523.
53. Baselga J, Campone M, Piccart M, et al. Everolimus in postmeno-pausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012; 366: 520-529.
54. Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007; 356: 2271-2281.
55. Salgia R. Prognostic significance of angiogenesis and angiogenic growth factors in nonsmall cell lung cancer. Cancer 2011; 117: 3889-3899.
56. O'Byrne KJ, Koukourakis MI, Giatromanolaki A, et al. Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer. Br J Cancer 2000; 82: 1427-1432.
57. Han H, Silverman JF, Santucci TS, et al. Vascular endothelial growth factor expression in stage I non-small cell lung cancer correlates with neoangiogenesis and a poor prognosis. Ann Surg Oncol 2001; 8: 72-79.
58. Yuan A, Yu CJ, Chen WJ, et al. Correlation of total VEGF mRNA and protein expression with histologic type, tumor angiogenesis, patient survival and timing of relapse in non-small-cell lung cancer. Int J Cancer 2000; 89: 475-483.
59. Delmotte P, Martin B, Paesmans M, et al. [VEGF and survival of patients with lung cancer: a systematic literature review and meta-analysis]. Rev Mal Respir 2002; 19: 577-584.
60. Zhan P, Wang J, Lv XJ, et al. Prognostic value of vascular endo-thelial growth factor expression in patients with lung cancer: a systematic review with meta-analysis. J Thorac Oncol 2009; 4: 1094-1103.
61. Bonnesen B, Pappot H, Holmstav J, Skov BG. Vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 expression in non-small cell lung cancer patients: relation to prognosis. Lung Cancer 2009; 66: 314-318.
62. Matsuyama M, Chijiwa T, Inoue Y, et al. Alternative splicing variant of vascular endothelial growth factor-A is a critical prognostic factor in non-small cell lung cancer. Oncol Rep 2009; 22: 1407-1413.
63. Jain RK, Duda DG, Willett CG, et al. Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 2009; 6: 327-338.
64. Yuan A, Lin CY, Chou CH, et al. Functional and structural characteristics of tumor angiogenesis in lung cancers overexpressing different VEGF isoforms assessed by DCE- and SSCE-MRI. PLoS One 2011; 6: e16062.
65. Yuan A, Yu CJ, Kuo SH, et al. Vascular endothelial growth factor 189 mRNA isoform expression specifically correlates with tumor angiogenesis, patient survival, and postoperative relapse in non-small-cell lung cancer. J Clin Oncol 2001; 19: 432-441.
66. Pajares MJ, Agorreta J, Larrayoz M, et al. Expression of Tumor-Derived Vascular Endothelial Growth Factor and Its Receptors Is Associated With Outcome in Early Squamous Cell Carcinoma of the Lung. J Clin Oncol 2012.
67. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005; 23: 1011-1027.
68. Arinaga M, Noguchi T, Takeno S, et al. Clinical significance of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in patients with nonsmall cell lung carcinoma. Cancer 2003; 97: 457-464.
69. Donnem T, Al-Saad S, Al-Shibli K, et al. Inverse prognostic impact of angiogenic marker expression in tumor cells versus stromal cells in non small cell lung cancer. Clin Cancer Res 2007; 13: 6649-6657.
70. Andersen S, Donnem T, Al-Saad S, et al. Angiogenic markers show high prognostic impact on survival in marginally operable non-small cell lung cancer patients treated with adjuvant radiotherapy. J Thorac Oncol 2009; 4: 463-471.
71. Seto T, Higashiyama M, Funai H, et al. Prognostic value of expression of vascular endothelial growth factor and its flt-1 and KDR receptors in stage I non-small-cell lung cancer. Lung Cancer 2006; 53: 91-96.
72. Carrillo de Santa Pau E, Arias FC, Caso Pelaez E, et al. Prognostic significance of the expression of vascular endothelial growth factors A, B, C, and D and their receptors R1, R2, and R3 in patients with nonsmall cell lung cancer. Cancer 2009; 115: 1701-1712.
73. Decaussin M, Sartelet H, Robert C, et al. Expression of vascular endothelial growth factor (VEGF) and its two receptors (VEGF-R1-Flt1 and VEGF-R2-Flk1/KDR) in non-small cell lung carcinomas (NSCLCs): correlation with angiogenesis and survival. J Pathol 1999; 188: 369-377.
74. Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev 2008; 22: 1276-1312.
75. Donnem T, Al-Saad S, Al-Shibli K, et al. Prognostic impact of platelet-derived growth factors in non-small cell lung cancer tumor and stromal cells. J Thorac Oncol 2008; 3: 963-970.
76. Donnem T, Al-Saad S, Al-Shibli K, et al. Co-expression of PDGF-B and VEGFR-3 strongly correlates with lymph node metastasis and poor survival in non-small-cell lung cancer. Ann Oncol 2012; 21: 223-231.
77. Korc M, Friesel RE. The role of fibroblast growth factors in tumor growth. Curr Cancer Drug Targets 2009; 9: 639-651.
78. Lund EL, Thorsen C, Pedersen MW, et al. Relationship between vessel density and expression of vascular endothelial growth factor and basic fibroblast growth factor in small cell lung cancer in vivo and in vitro. Clin Cancer Res 2000; 6: 4287-91.
79. Brattstrom D, Bergqvist M, Larsson A, et al. Basic fibroblast growth factor and vascular endothelial growth factor in sera from non-small cell lung cancer patients. Anticancer Res 1998; 18: 1123-1127.
80. Brattstrom D, Bergqvist M, Hesselius P, et al. Elevated preopera-tive serum levels of angiogenic cytokines correlate to larger primary tumours and poorer survival in non-small cell lung cancer patients. Lung Cancer 2002; 37: 57-63.
81. Joensuu H, Anttonen A, Eriksson M, et al. Soluble syndecan-1 and serum basic fibroblast growth factor are new prognostic factors in lung cancer. Cancer Res 2002; 62: 5210-5217.
82. Iwasaki A, Kuwahara M, Yoshinaga Y, Shirakusa T. Basic fibro-blast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels, as prognostic indicators in NSCLC. Eur J Car-diothorac Surg 2004; 25: 443-448.
83. Choi WW, Lewis MM, Lawson D, et al. Angiogenic and lymphan-giogenic microvessel density in breast carcinoma: correlation with clinicopathologic parameters and VEGF-family gene expression. Mod Pathol 2005; 18: 143-152.
84. Meert AP, Paesmans M, Martin B, et al. The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer 2002; 87: 694-701.
85. Trivella M, Pezzella F, Pastorino U, et al. Microvessel density as a prognostic factor in non-small-cell lung carcinoma: a meta-analysis of individual patient data. Lancet Oncol 2007; 8: 488-499.
86. Chen ZJ, Le HB, Zhang YK, et al. Microvessel density and expression of thrombospondin-1 in non-small cell lung cancer and their correlation with clinicopathological features. J Int Med Res 2009; 37: 551-556.
87. Cherni I, Weiss GJ. miRNAs in lung cancer: large roles for small players. Future Oncol 2011; 7: 1045-1055.
88. Ortholan C, Puissegur MP, Ilie M, et al. MicroRNAs and lung cancer: new oncogenes and tumor suppressors, new prognostic factors and potential therapeutic targets. Curr Med Chem 2009; 16: 1047-1061.
89. Yanaihara N, Caplen N, Bowman E, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 2006; 9: 189-198.
90. Johnson CD, Esquela-Kerscher A, Stefani G, et al. The let-7 mi-croRNA represses cell proliferation pathways in human cells. Cancer Res 2007; 67: 7713-7722.
91. Kumar MS, Erkeland SJ, Pester RE, et al. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci USA 2008; 105: 3903-3908.
92. Kluiver J, Poppema S, de Jong D, et al. BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas. J Pathol 2005; 207: 243-249.
93. Hayashita Y, Osada H, Tatematsu Y, et al. A polycistronic mi-croRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 2005; 65: 9628-9632.
94. Zhu S, Wu H, Wu F, et al. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res 2008; 18: 350-359.
95. Fabbri M, Garzon R, Cimmino A, et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci USA 2007; 104: 15805-15810.
96. le Sage C, Nagel R, Egan DA, et al. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J 2007; 26: 3699-3708.
97. Graves EE, Maity A, Le QT. The tumor microenvironment in non-small-cell lung cancer. Semin Radiat Oncol 2010; 20: 156-163.
98. Yuan A, Chen JJ, Yao PL, Yang PC. The role of interleukin-8 in cancer cells and microenvironment interaction. Front Biosci 2005; 10: 853-865.
99. Yuan A, Yang PC, Yu CJ, et al. Interleukin-8 messenger ribonu-cleic acid expression correlates with tumor progression, tumor an-giogenesis, patient survival, and timing of relapse in non-small-cell lung cancer. Am J Respir Crit Care Med 2000; 162: 1957-1963.
100. Zhang Y, Wang L, Zhang M, et al. Potential mechanism of inter-leukin-8 production from lung cancer cells: an involvement of EGF-EGFR-PI3K-Akt-Erk pathway. J Cell Physiol 2012; 227: 35-43.
101. Chen X, Wan J, Liu J, et al. Increased IL-17-producing cells correlate with poor survival and lymphangiogenesis in NSCLC patients. Lung Cancer 2010; 69: 348-354.
102. Krysan K, Reckamp KL, Sharma S, Dubinett SM. The potential and rationale for COX-2 inhibitors in lung cancer. Anticancer Agents Med Chem 2006; 6: 209-220.
103. Tsubochi H, Sato N, Hiyama M, et al. Combined analysis of cy-clooxygenase-2 expression with p53 and Ki-67 in nonsmall cell lung cancer. Ann Thorac Surg 2006; 82: 1198-1204.
104. Yuan A, Yu CJ, Shun CT, et al. Total cyclooxygenase-2 mRNA levels correlate with vascular endothelial growth factor mRNA levels, tumor angiogenesis and prognosis in non-small cell lung cancer patients. Int J Cancer 2005; 115: 545-555.
105. Nakashima T, Huang C, Liu D, et al. Neural-cadherin expression associated with angiogenesis in non-small-cell lung cancer patients. Br J Cancer 2003; 88: 1727-1733.
106. Gogali A, Charalabopoulos K, Zampira I, et al. Soluble adhesion molecules E-cadherin, intercellular adhesion molecule-1, and E-selectin as lung cancer biomarkers. Chest 2012; 138: 1173-1179.
107. Chang H, Iizasa T, Shibuya K, et al. Increased expression of collagen XVIII and its prognostic value in nonsmall cell lung carcinoma. Cancer 2004; 100: 1665-1672.
108. Iizasa T, Chang H, Suzuki M, et al. Overexpression of collagen XVIII is associated with poor outcome and elevated levels of circulating serum endostatin in non-small cell lung cancer. Clin Cancer Res 2004; 10: 5361-5366.
109. Reck M, von Pawel J, Zatloukal P, et al. 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.
110. Herbst RS, Ansari R, Bustin F, et al. 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.
111. Patel JD, Bonomi P, Socinski MA, et al. Treatment rationale and study design for the pointbreak study: a randomized, open-label phase III study of pemetrexed/carboplatin/bevacizumab followed by maintenance pemetrexed/bevacizumab versus pacli-taxel/carboplatin/bevacizumab followed by maintenance bevaci-zumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. Clin Lung Cancer 2009; 10: 252-256.
112. Crino L, Dansin E, Garrido P, et al. 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.
113. Ulahannan SV, Brahmer JR. Antiangiogenic agents in combination with chemotherapy in patients with advanced non-small cell lung cancer. Cancer Invest 2011; 29: 325-337.
114. Scagliotti G, Novello S, von Pawel J, et al. Phase III study of car-boplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol 2012; 28: 1835-1842.
115. Paz-Ares LG, Biesma B, Heigener D, et al. Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. J Clin Oncol 2012; 30: 3084-3092.
116. Blumenschein GR, Jr., Gatzemeier U, Fossella F, et al. Phase II, multicenter, uncontrolled trial of single-agent sorafenib in patients with relapsed or refractory, advanced non-small-cell lung cancer. J Clin Oncol 2009; 27: 4274-4280.
117. Dy GK, Hillman SL, Rowland KM, Jr., et al. A front-line window of opportunity phase 2 study of sorafenib in patients with advanced nonsmall cell lung cancer: North Central Cancer Treatment Group Study N0326. Cancer 2010; 116: 5686-5693.
118. Lind JS, Dingemans AM, Groen HJ, et al. A multicenter phase II study of erlotinib and sorafenib in chemotherapy-naive patients with advanced non-small cell lung cancer. Clin Cancer Res 2010; 16: 3078-3087.
119. Spigel DR, Burris HA, 3rd, Greco FA, et al. Randomized, double-blind, placebo-controlled, phase II trial of sorafenib and erlotinib or erlotinib alone in previously treated advanced non-small-cell lung cancer. J Clin Oncol 2011; 29: 2582-2589.
120. Scagliotti GV, Krzakowski M, Szczesna A, et al. Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer: a phase III trial. J Clin Oncol 2012; 30: 2070-2078.
121. Novello S, Scagliotti GV, Rosell R, et al. Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer. Br J Cancer 2009; 101: 1543-1548.
122. Socinski MA, Novello S, Brahmer JR, et al. Multicenter, phase II trial of sunitinib in previously treated, advanced non-small-cell lung cancer. J Clin Oncol 2008; 26: 650-656.
123. Schneider BJ, Gadgeel SM, Ramnath N, et al. Phase II trial of sunitinib maintenance therapy after platinum-based chemotherapy in patients with extensive-stage small cell lung cancer. J Thorac Oncol 2011; 6: 1117-1120.
124. Gervais R, Hainsworth JD, Blais N, et al. Phase II study of sunit-inib as maintenance therapy in patients with locally advanced or metastatic non-small cell lung cancer. Lung Cancer 2011; 74: 474-480.
125. Heymach JV, Paz-Ares L, De Braud F, et al. Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer. J Clin Oncol 2008; 26: 5407-5415.
126. Heymach JV, Johnson BE, Prager D, et al. Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non small-cell lung cancer. J Clin Oncol 2007; 25: 4270-4277.
127. Natale RB, Bodkin D, Govindan R, et al. Vandetanib versus gefit-inib in patients with advanced non-small-cell lung cancer: results from a two-part, double-blind, randomized phase ii study. J Clin Oncol 2009; 27: 2523-2529.
128. Herbst RS, Sun Y, Eberhardt WE, et al. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol 2010; 11: 619-626.
129. de Boer RH, Arrieta O, Yang CH, et al. Vandetanib plus pe-metrexed for the second-line treatment of advanced non-small-cell lung cancer: a randomized, double-blind phase III trial. J Clin Oncol 2012; 29: 1067-1074.
130. Natale RB, Thongprasert S, Greco FA, et al. Phase III trial of vandetanib compared with erlotinib in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol 2011; 29: 1059-1066.
131. Lee JS, Hirsh V, Park K, et al. Vandetanib Versus placebo in patients with advanced non-small-cell lung cancer after prior therapy with an epidermal growth factor receptor tyrosine kinase inhibitor: a randomized, double-blind phase III trial (ZEPHYR). J Clin Oncol 2012; 30: 1114-1121.
132. Gaya A, Tse V. A preclinical and clinical review of aflibercept for the management of cancer. Cancer Treat Rev 2012.
133. Leighl NB, Raez LE, Besse B, et al. A multicenter, phase 2 study of vascular endothelial growth factor trap (Aflibercept) in platinum- and erlotinib-resistant adenocarcinoma of the lung. J Thorac Oncol 2010; 5: 1054-1059.
134. Gotlieb WH, Amant F, Advani S, et al. Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Oncol 2012.
135. Colombo N, Mangili G, Mammoliti S, et al. A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites. Gynecol Oncol 2011.
136. de Groot JF, Lamborn KR, Chang SM, et al. Phase II study of aflibercept in recurrent malignant glioma: a North American Brain Tumor Consortium study. J Clin Oncol 2011; 29: 2689-2695.
137. Ramlau R, Gorbunova V, Ciuleanu TE, et al. Aflibercept and Do-cetaxel versus Docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial. J Clin Oncol 2012; 30: 3640-3647.
138. Siemann DW. The unique characteristics of tumor vasculature and preclinical evidence for its selective disruption by Tumor-Vascular Disrupting Agents. Cancer Treat Rev 2011; 37: 63-74.
139. McKeage MJ, Von Pawel J, Reck M, et al. Randomised phase II study of ASA404 combined with carboplatin and paclitaxel in previously untreated advanced non-small cell lung cancer. Br J Cancer 2008; 99: 2006-2012.
140. McKeage MJ, Reck M, Jameson MB, et al. Phase II study of ASA404 (vadimezan, 5,6-dimethylxanthenone-4-acetic acid/DMXAA) 1800mg/m(2) combined with carboplatin and paclitaxel in previously untreated advanced non-small cell lung cancer. Lung Cancer 2009; 65: 192-197.
141. Lara PN, Jr., Douillard JY, Nakagawa K, et al. Randomized phase III placebo-controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent vadimezan (ASA404) in advanced non-small-cell lung cancer. J Clin Oncol 2011; 29: 2965-2971.
142. Blumenschein GR, Jr., Kabbinavar F, Menon H, et al. A phase II, multicenter, open-label randomized study of motesanib or bevaci-zumab in combination with paclitaxel and carboplatin for advanced nonsquamous non-small-cell lung cancer. Ann Oncol 2011; 22: 2057-2067.
143. Scagliotti GV, Vynnychenko I, Park K, et al. International, randomized, placebo-controlled, double-blind phase III study of mote-sanib plus carboplatin/paclitaxel in patients with advanced non-squamous non-small-cell lung cancer: MONET1. J Clin Oncol 2012; 30: 2829-2836.
144. Sessa C, Guibal A, Del Conte G, Ruegg C. Biomarkers of angio-genesis for the development of antiangiogenic therapies in oncology: tools or decorations? Nat Clin Pract Oncol 2008; 5: 378-391.
145. Dancey JE, Dobbin KK, Groshen S, et al. Guidelines for the development and incorporation of biomarker studies in early clinical trials of novel agents. Clin Cancer Res 2010; 16: 1745-1755.
146. Daenen LGM, Voest, E. Finding Predictive Biomarkers for Anti-Vascular Endothelial Growth Factor Treatment: A Mission Impossible? In Proceedings of the Americal Society of Clinical Oncology Meeting Chicago (US): Journal of Clinical Oncology 2011; 429-433.
147. Huang D, Ding Y, Zhou M, et al. Interleukin-8 mediates resistance to antiangiogenic agent sunitinib in renal cell carcinoma. Cancer Res 2010; 70: 1063-1071.
148. Xu CF, Bing NX, Ball HA, et al. Pazopanib efficacy in renal cell carcinoma: evidence for predictive genetic markers in angiogene-sis-related and exposure-related genes. J Clin Oncol 2011; 29: 2557-2564.
149. Kopetz S, Hoff PM, Morris JS, et al. Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance. J Clin Oncol 2010; 28: 453-459.
150. Dowlati A, Gray R, Sandler AB, et al. Cell adhesion molecules, vascular endothelial growth factor, and basic fibroblast growth factor in patients with non-small cell lung cancer treated with chemotherapy with or without bevacizumab--an Eastern Cooperative Oncology Group Study. Clin Cancer Res 2008; 14: 1407-1412.
151. Hanrahan EO, Ryan AJ, Mann H, et al. Baseline vascular endothe-lial growth factor concentration as a potential predictive marker of benefit from vandetanib in non-small cell lung cancer. Clin Cancer Res 2009; 15: 3600-3609.
152. Nikolinakos PG, Altorki N, Yankelevitz D, et al. Plasma cytokine and angiogenic factor profiling identifies markers associated with tumor shrinkage in early-stage non-small cell lung cancer patients treated with pazopanib. Cancer Res 2010; 70: 2171-2179.
153. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376: 687-697.
154. Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006; 355: 2733-2743.
155. Wells SA, Jr., Gosnell JE, Gagel RF, et al. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol 2010; 28: 767-772.
156. Schiller JH, Larson T, Ou SH, et al. Efficacy and safety of axitinib in patients with advanced non-small-cell lung cancer: results from a phase II study. J Clin Oncol 2009; 27: 3836-3841.
157. Kindler HL, Ioka T, Richel DJ, et al. Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study. Lancet Oncol 12: 256-262.
158. Rugo HS, Stopeck AT, Joy AA, et al. Randomized, placebo-controlled, double-blind, phase II study of axitinib plus docetaxel versus docetaxel plus placebo in patients with metastatic breast cancer. J Clin Oncol 2011; 29: 2459-2465.
159. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364: 2507-2516.
160. Miller VA, Hirsh V, Cadranel J, et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol 2012; 13: 528-538.
161. Martin M, Roche H, Pinter T, et al. Motesanib, or open-label bevacizumab, in combination with paclitaxel, as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Oncol 12: 369-376.
162. Schlumberger MJ, Elisei R, Bastholt L, et al. Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol 2009; 27: 3794-3801.
163. Van Cutsem E, Bajetta E, Valle J, et al. Randomized, placebo-controlled, phase III study of oxaliplatin, fluorouracil, and leuco-vorin with or without PTK787/ZK 222584 in patients with previously treated metastatic colorectal adenocarcinoma. J Clin Oncol 29: 2004-2010.
164. Gauler TC, Besse B, Mauguen A, et al. 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 2012.
165. Joensuu H, De Braud F, Grignagni G, et al. Vatalanib for metas-tatic gastrointestinal stromal tumour (GIST) resistant to imatinib: final results of a phase II study. Br J Cancer 104: 1686-1690.
166. Hecht JR, Trarbach T, Hainsworth JD, et al. Randomized, placebo-controlled, phase III study of first-line oxaliplatin-based chemotherapy plus PTK787/ZK 222584, an oral vascular endothelial growth factor receptor inhibitor, in patients with metastatic colorec-tal adenocarcinoma. J Clin Oncol 29: 1997-2003.
167. Cook N, Basu B, Biswas S, et al. A phase 2 study of vatalanib in metastatic melanoma patients. Eur J Cancer 2010; 46: 2671-2673.
168. Goss GD, Arnold A, Shepherd FA, et al. Randomized, double-blind trial of carboplatin and paclitaxel with either daily oral cediranib or placebo in advanced non-small-cell lung cancer: NCIC clinical trials group BR24 study. J Clin Oncol 2010; 28: 49-55.
169. Batchelor TT, Duda DG, di Tomaso E, et al. Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. J Clin Oncol 2010; 28: 2817-2823.
170. Ramalingam SS, Belani CP, Mack PC, et al. Phase II study of Cediranib (AZD 2171), an inhibitor of the vascular endothelial growth factor receptor, for second-line therapy of small cell lung cancer (National Cancer Institute #7097). J Thorac Oncol 2010; 5: 1279-1284.
171. Gerber DE, Stopeck AT, Wong L, et al. Phase I safety and pharma-cokinetic study of bavituximab, a chimeric phosphatidylserine-targeting monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res 2011; 17: 6888-6896.
172. Tan EH, Goss GD, Salgia R, et al. Phase 2 trial of Linifanib (ABT-869) in patients with advanced non-small cell lung cancer. J Thorac Oncol 2011; 6: 1418-1425.
173. Tannir NM, Wong YN, Kollmannsberger CK, et al. Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure. Eur J Cancer 2011; 47: 2706-2714.
174. Reck M, Kaiser R, Eschbach C, et al. A phase II double-blind study to investigate efficacy and safety of two doses of the triple angi-okinase inhibitor BIBF 1120 in patients with relapsed advanced non-small-cell lung cancer. Ann Oncol 2011; 22: 1374-1381.
175. Ledermann JA, Hackshaw A, Kaye S, et al. Randomized phase II placebo-controlled trial of maintenance therapy using the oral triple angiokinase inhibitor BIBF 1120 after chemotherapy for relapsed ovarian cancer. J Clin Oncol 2011; 29: 3798-3804.
176. Bell-McGuinn KM, Matthews CM, Ho SN, et al. A phase II, single-arm study of the anti-alpha5beta1 integrin antibody volocixi-mab as monotherapy in patients with platinum-resistant advanced epithelial ovarian or primary peritoneal cancer. Gynecol Oncol 2011; 121: 273-279.
177. Ng QS, Mandeville H, Goh V, et al. Phase Ib trial of radiotherapy in combination with combretastatin-A4-phosphate in patients with non-small-cell lung cancer, prostate adenocarcinoma, and squamous cell carcinoma of the head and neck. Ann Oncol 2011; 23: 231-237.
178. Mita MM, Spear MA, Yee LK, et al. Phase 1 first-in-human trial of the vascular disrupting agent plinabulin(NPI-2358) in patients with solid tumors or lymphomas. Clin Cancer Res 2010; 16: 5892-5899.
179. Zhao X, Mei K, Cai X, et al. A randomized phase II study of re-combinant human endostatin plus gemcitabine/cisplatin compared with gemcitabine/cisplatin alone as first-line therapy in advanced non-small-cell lung cancer. Invest New Drugs 2012.
180. Tolcher AW, Sweeney CJ, Papadopoulos K, et al. Phase I and pharmacokinetic study of CT-322 (BMS-844203), a targeted Ad-nectin inhibitor of VEGFR-2 based on a domain of human fi-bronectin. Clin Cancer Res 2011; 17: 363-371.
181. Gauler TC, Besse B, Mauguen A, et al. 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.
182. Altorki N, Lane ME, Bauer T, et al. Phase II proof-of-concept study of pazopanib monotherapy in treatment-naive patients with stage I/II resectable non-small-cell lung cancer. J Clin Oncol 2010; 28: 3131-7.