Anti-VEGF strategies - from antibodies to tyrosine kinase inhibitors: Background and clinical development in human cancer

Current Pharmaceutical Design

Volumn 18, Issue 19, 2012, Pages 2680-2701

  Korpanty, Grzegorz ^a   Smyth, Elizabeth ^a  

^a BEAUMONT HOSPITAL   (Ireland)

Author keywords

Anti angiogenic therapy; Tumour angiogenesis; Tyrosine kinase inhibitors; Vascular endothelial growth factor

Indexed keywords

AFLIBERCEPT; ALPHA2A INTERFERON; ANTHRACYCLINE; BEVACIZUMAB; CAPECITABINE; CAPECITABINE PLUS OXALIPLATIN; CARBOPLATIN; CISPLATIN; CYCLOPHOSPHAMIDE; DOCETAXEL; DOXORUBICIN; EPIRUBICIN; FLUOROURACIL; FOLINIC ACID; GEMCITABINE; IRINOTECAN; METALLOPROTEINASE; NAVELBINE; NITRIC OXIDE SYNTHASE; OXALIPLATIN; PACLITAXEL; PAZOPANIB; PROTEIN TYROSINE KINASE INHIBITOR; RANIBIZUMAB; SORAFENIB; SUNITINIB; TAXANE DERIVATIVE; VASCULOTROPIN; VASCULOTROPIN ANTIBODY;

ANGIOGENESIS; ANTIANGIOGENIC THERAPY; APOPTOSIS; ARTICLE; BINDING AFFINITY; BLEEDING; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CANCER PROGNOSIS; CANCER RADIOTHERAPY; CANCER STAGING; CANCER SURGERY; CANCER SURVIVAL; CARCINOGENESIS; CARDIOTOXICITY; CELL MEMBRANE PERMEABILITY; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; COLORECTAL CANCER; DIARRHEA; DIGESTIVE SYSTEM PERFORATION; DISEASE COURSE; DRUG APPROVAL; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; ENDOTHELIUM CELL; ENZYME ACTIVITY; EXTRACELLULAR MATRIX; FATIGUE; FEBRILE NEUTROPENIA; FOOD AND DRUG ADMINISTRATION; GASTROINTESTINAL STROMAL TUMOR; GLIOBLASTOMA; HAND FOOT SYNDROME; HEADACHE; HUMAN; HYPERTENSION; HYPONATREMIA; HYPOXIA; KIDNEY CARCINOMA; LIGAND BINDING; LIVER CELL CARCINOMA; LUNG HEMORRHAGE; LUNG NON SMALL CELL CANCER; LYMPHOCYTOPENIA; MELANOMA; MOLECULARLY TARGETED THERAPY; MULTICENTER STUDY (TOPIC); MULTIMODALITY CANCER THERAPY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEPHRECTOMY; NEUTROPENIA; NONHUMAN; OVARY CANCER; OVERALL SURVIVAL; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; RECEPTOR BINDING; SIDE EFFECT; SIGNAL TRANSDUCTION; THROMBOCYTOPENIA; THYROID CANCER; TREATMENT DURATION; TUMOR MICROENVIRONMENT; VASCULAR ENDOTHELIUM;

EID: 84862585045     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161212800626166     Document Type: Article

References (257)

1. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995; 1(1): 27-31.
2. Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer 2002; 2(10): 795-803.
3. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285(21): 1182-6.
4. Ribatti D. Judah Folkman, a pioneer in the study of angiogenesis. Angiogenesis 2008; 11(1): 3-10.
5. Folkman J, Merler E, Abernathy C, Williams G. Isolation of a tumor factor responsible for angiogenesis. J Exp Med 1971; 133(2): 275-88.
6. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983; 219(4587): 983-5.
7. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989; 246(4935): 1306-9.
8. Keck PJ, Hauser SD, Krivi G, et al. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 1989; 246(4935): 1309-12.
9. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003; 9(6): 669-76.
10. Takahashi H, Shibuya M. The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clin Sci (Lond) 2005; 109(3): 227-41.
11. Hiratsuka S, Minowa O, Kuno J, Noda T, Shibuya M. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci USA 1998; 95(16): 9349-54.
12. Lyden D, Hattori K, Dias S, et al. Impaired recruitment of bonemarrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001; 7(11): 1194-201.
13. Robinson CJ, Stringer SE. The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J Cell Sci 2001; 114(Pt 5): 853-65.
14. Shibuya M. Vascular endothelial growth factor (VEGF)-Receptor2: its biological functions, major signaling pathway, and specific ligand VEGF-E. Endothelium 2006; 13(2): 63-9.
15. Fong GH, Rossant J, Gertsenstein M, Breitman ML. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995; 376(6535): 66-70.
16. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004; 25(4): 581-611.
17. Holmes K, Roberts OL, Thomas AM, Cross MJ. Vascular endothelial growth factor receptor-2: Structure, function, intracellular signalling and therapeutic inhibition. Cell Signal 2007; 19(10): 2003-12.
18. Dougher M, Terman BI. Autophosphorylation of KDR in the kinase domain is required for maximal VEGF-stimulated kinase activity and receptor internalization. Oncogene 1999; 18(8): 1619-27.
19. Takahashi T, Yamaguchi S, Chida K, Shibuya M. A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells. Embo J 2001; 20(11): 2768-78.
20. Fujio Y, Walsh K. Akt mediates cytoprotection of endothelial cells by vascular endothelial growth factor in an anchorage-dependent manner. J Biol Chem 1999; 274(23): 16349-54.
21. Roberts WG, Palade GE. Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 1995; 108 (Pt 6): 2369-79.
22. Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling in control of vascular function. Nat Rev Mol Cell Biol 2006; 7(5): 359-71.
23. Abedi H, Zachary I. Vascular endothelial growth factor stimulates tyrosine phosphorylation and recruitment to new focal adhesions of focal adhesion kinase and paxillin in endothelial cells. J Biol Chem 1997; 272(24): 15442-51.
24. Yamaoka-Tojo M, Ushio-Fukai M, Hilenski L, et al. IQGAP1, a novel vascular endothelial growth factor receptor binding protein, is involved in reactive oxygen species--dependent endothelial migration and proliferation. Circ Res 2004; 95(3): 276-83.
25. He Y, Rajantie I, Pajusola K, et al. Vascular endothelial cell growth factor receptor 3-mediated activation of lymphatic endothelium is crucial for tumor cell entry and spread via lymphatic vessels. Cancer Res 2005; 65(11): 4739-46.
26. He Y, Kozaki K, Karpanen T, et al. Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling. J Natl Cancer Inst 2002; 94(11): 819-25.
27. Neufeld G, Cohen T, Shraga N, Lange T, Kessler O, Herzog Y. The neuropilins: multifunctional semaphorin and VEGF receptors that modulate axon guidance and angiogenesis. Trends Cardiovasc Med 2002; 12(1): 13-9.
28. Soker S, Fidder H, Neufeld G, Klagsbrun M. Characterization of novel vascular endothelial growth factor (VEGF) receptors on tumor cells that bind VEGF165 via its exon 7-encoded domain. J Biol Chem 1996; 271(10): 5761-7.
29. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 1998; 92(6): 735-45.
30. Safran M, Kaelin WG, Jr. HIF hydroxylation and the mammalian oxygen-sensing pathway. J Clin Invest 2003; 111(6): 779-83.
31. Wang GL, Semenza GL. Purification and characterization of hypoxia-inducible factor 1. J Biol Chem 1995; 270(3): 1230-7.
32. Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA 1995; 92(12): 5510-4.
33. Semenza GL. HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus. Cell 2001; 107(1): 1-3.
34. Levy AP, Levy NS, Wegner S, Goldberg MA. Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J Biol Chem 1995; 270(22): 13333-40.
35. Cohen T, Nahari D, Cerem LW, Neufeld G, Levi BZ. Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem 1996; 271(2): 736-41.
36. Frank S, Hubner G, Breier G, Longaker MT, Greenhalgh DG, Werner S. Regulation of vascular endothelial growth factor expression in cultured keratinocytes. Implications for normal and impaired wound healing. J Biol Chem 1995; 270(21): 12607-13.
37. Pertovaara L, Kaipainen A, Mustonen T, et al. Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells. J Biol Chem 1994; 269(9): 6271-4.
38. Warren RS, Yuan H, Matli MR, Ferrara N, Donner DB. Induction of vascular endothelial growth factor by insulin-like growth factor 1 in colorectal carcinoma. J Biol Chem 1996; 271(46): 29483-8.
39. Ben-Av P, Crofford LJ, Wilder RL, Hla T. Induction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin E and interleukin-1: a potential mechanism for inflammatory angiogenesis. FEBS Lett 1995 Sep 18; 372(1): 83-7.
40. Li YQ, Tao KS, Ren N, Wang YH. Effect of c-fos antisense probe on prostaglandin E2-induced upregulation of vascular endothelial growth factor mRNA in human liver cancer cells. World J Gastroenterol 2005; 11(28): 4427-30.
41. Grugel S, Finkenzeller G, Weindel K, Barleon B, Marme D. Both v-Ha-Ras and v-Raf stimulate expression of the vascular endothelial growth factor in NIH 3T3 cells. J Biol Chem 1995; 270(43): 25915-9.
42. Okada F, Rak JW, Croix BS, et al. Impact of oncogenes in tumor angiogenesis: mutant K-ras up-regulation of vascular endothelial growth factor/vascular permeability factor is necessary, but not sufficient for tumorigenicity of human colorectal carcinoma cells. Proc Natl Acad Sci USA 1998; 95(7): 3609-14.
43. Wey JS, Stoeltzing O, Ellis LM. Vascular endothelial growth factor receptors: expression and function in solid tumors. Clin Adv Hematol Oncol 2004; 2(1): 37-45.
44. 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(4): 369-77.
45. Lantuejoul S, Constantin B, Drabkin H, Brambilla C, Roche J, Brambilla E. Expression of VEGF, semaphorin SEMA3F, and their common receptors neuropilins NP1 and NP2 in preinvasive bronchial lesions, lung tumours, and cell lines. J Pathol 2003; 200(3): 336-47.
46. Castro-Rivera E, Ran S, Thorpe P, Minna JD. Semaphorin 3B (SEMA3B) induces apoptosis in lung and breast cancer, whereas VEGF165 antagonizes this effect. Proc Natl Acad Sci USA 2004; 101(31): 11432-7.
47. Nasarre P, Constantin B, Rouhaud L, et al. Semaphorin SEMA3F and VEGF have opposing effects on cell attachment and spreading. Neoplasia 2003; 5(1): 83-92.
48. Okazaki T, Ebihara S, Asada M, Kanda A, Sasaki H, Yamaya M. Granulocyte colony-stimulating factor promotes tumor angiogenesis via increasing circulating endothelial progenitor cells and Gr1+CD11b+ cells in cancer animal models. Int Immunol 2006; 18(1): 1-9.
49. De Palma M, Venneri MA, Galli R, et al. Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 2005; 8(3): 211-26.
50. Venneri MA, De Palma M, Ponzoni M, et al. Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer. Blood 2007 Jun 15; 109(12): 5276-85.
51. Conejo-Garcia JR, Buckanovich RJ, Benencia F, et al. Vascular leukocytes contribute to tumor vascularization. Blood 2005; 105(2): 679-81.
52. Grunewald M, Avraham I, Dor Y, et al. VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell 2006; 124(1): 175-89.
53. Bertolini F, Shaked Y, Mancuso P, Kerbel RS. The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat Rev Cancer 2006; 6(11): 835-45.
54. Peters BA, Diaz LA, Polyak K, et al. Contribution of bone marrow-derived endothelial cells to human tumor vasculature. Nat Med 2005; 11(3): 261-2.
55. Garcia-Barros M, Paris F, Cordon-Cardo C, et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science 2003; 300(5622): 1155-9.
56. Spring H, Schuler T, Arnold B, Hammerling GJ, Ganss R. Chemokines direct endothelial progenitors into tumor neovessels. Proc Natl Acad Sci USA 2005 Dec 13; 102(50): 18111-6.
57. Shaked Y, Ciarrocchi A, Franco M, et al. Therapy-induced acute recruitment of circulating endothelial progenitor cells to tumors. Science 2006; 313(5794): 1785-7.
58. Siemann DW, Chaplin DJ, Horsman MR. Vascular-targeting therapies for treatment of malignant disease. Cancer 2004; 100(12): 2491-9.
59. Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature 2005 Dec 15; 438(7070): 967-74.
60. Ferrara N, Hillan KJ, Gerber HP, Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 2004; 3(5): 391-400.
61. Kim KJ, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 1993; 362(6423): 841-4.
62. 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(20): 4593-9.
63. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350(23): 2335-42.
64. Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007; 25(12): 1539-44.
65. Jain RK, Duda DG, Clark JW, Loeffler JS. Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol 2006; 3(1): 24-40.
66. Medina MA, Munoz-Chapuli R, Quesada AR. Challenges of antiangiogenic cancer therapy: trials and errors, and renewed hope. J Cell Mol Med 2007; 11(3): 374-82.
67. Aflibercept: AVE 0005, AVE 005, AVE0005, VEGF Trap Regeneron, VEGF Trap (R1R2), VEGF Trap-Eye. Drugs R D 2008; 9(4): 261-9.
68. Steinbrook R. The price of sight--ranibizumab, bevacizumab, and the treatment of macular degeneration. N Engl J Med 2006 Oct 5; 355(14): 1409-12.
69. Stewart MW, Rosenfeld PJ. Predicted biological activity of intravitreal VEGF Trap. Br J Ophthalmol 2008; 92(5): 667-8.
70. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006; 355(14): 1419-31.
71. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006; 355(14): 1432-44.
72. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science 2002; 298(5600): 1912-34.
73. Liu Y, Gray NS. Rational design of inhibitors that bind to inactive kinase conformations. Nat Chem Biol 2006; 2(7): 358-64.
74. Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2000; 103(2): 211-25.
75. Hubbard SR, Miller WT. Receptor tyrosine kinases: mechanisms of activation and signaling. Curr Opin Cell Biol 2007; 19(2): 117-23.
76. Pawson T. Specificity in signal transduction: from phosphor-tyrosine-SH2 domain interactions to complex cellular systems. Cell 2004; 116(2): 191-203.
77. Zhang J, Yang PL, Gray NS. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer 2009; 9(1): 28-39.
78. 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(1): 327-37.
79. Faivre S, Demetri G, Sargent W, Raymond E. Molecular basis for sunitinib efficacy and future clinical development. Nat Rev Drug Discov 2007; 6(9): 734-45.
80. Johnson LN. Protein kinase inhibitors: contributions from structure to clinical compounds. Q Rev Biophys 2009; 42(1): 1-40.
81. Kwak EL, Sordella R, Bell DW, et al. Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Proc Natl Acad Sci USA 2005; 102(21): 7665-70.
82. Wan PT, Garnett MJ, Roe SM, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of BRAF. Cell 2004; 116(6): 855-67.
83. Krause DS, Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med 2005; 353(2): 172-87.
84. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007; 356(2): 115-24.
85. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359(4): 378-90.
86. Kerbel RS. Inhibition of tumor angiogenesis as a strategy to circumvent acquired resistance to anti-cancer therapeutic agents. Bioessays 1991; 13(1): 31-6.
87. Klement G, Baruchel S, Rak J, et al. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest 2000; 105(8): R15-24.
88. Browder T, Butterfield CE, Kraling BM, et al. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 2000; 60(7): 1878-86.
89. Hanahan D, Bergers G, Bergsland E. Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. J Clin Invest 2000; 105(8): 1045-7.
90. Pasquier E, Kavallaris M, Andre N. Metronomic chemotherapy: new rationale for new directions. Nat Rev Clin Oncol.; 7(8): 455-65.
91. Miller KD, Sweeney CJ, Sledge GW, Jr. Redefining the target: chemotherapeutics as antiangiogenics. J Clin Oncol 2001; 19(4): 1195-206.
92. Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological aspects of cancer chemotherapy. Nat Rev Immunol 2008; 8(1): 59-73.
93. Aguirre-Ghiso JA. Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 2007; 7(11): 834-46.
94. Jubb AM, Oates AJ, Holden S, Koeppen H. Predicting benefit from anti-angiogenic agents in malignancy. Nat Rev Cancer 2006; 6(8): 626-35.
95. Jaffe CC. Measures of response: RECIST, WHO, and new alternatives. J Clin Oncol 2006; 24(20): 3245-51.
96. Duda DG, Jain RK, Willett CG. Antiangiogenics: the potential role of integrating this novel treatment modality with chemoradiation for solid cancers. J Clin Oncol 2007; 25(26): 4033-42.
97. Akslen LA, Naumov GN. Tumor dormancy--from basic mechanisms to clinical practice. Apmis 2008; 116(7-8): 545-7.
98. Naumov GN, Folkman J, Straume O, Akslen LA. Tumor-vascular interactions and tumor dormancy. Apmis 2008; 116(7-8): 569-85.
99. Carmeliet P. Angiogenesis in life, disease and medicine. Nature 2005; 438(7070): 932-6.
100. Greenberg JI, Shields DJ, Barillas SG, et al. A role for VEGF as a negative regulator of pericyte function and vessel maturation. Nature 2008; 456(7223): 809-13.
101. Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001; 7(9): 987-9.
102. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005; 307(5706): 58-62.
103. Jain RK. Transport of molecules in the tumor interstitium: a review. Cancer Res 1987; 47(12): 3039-51.
104. Dings RP, Loren M, Heun H, et al. Scheduling of radiation with angiogenesis inhibitors anginex and Avastin improves therapeutic outcome via vessel normalization. Clin Cancer Res 2007; 13(11): 3395-402.
105. Koopman M, Antonini NF, Douma J, et al. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet 2007; 370(9582): 135-42.
106. Seymour MT, Maughan TS, Ledermann JA, et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet 2007 Jul 14; 370(9582): 143-52.
107. Kabbinavar F, Hurwitz HI, Fehrenbacher L, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003; 21(1): 60-5.
108. Hurwitz HI, Fehrenbacher L, Hainsworth JD, et al. Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J Clin Oncol 2005; 23(15): 3502-8.
109. Allegra CJ, Yothers G, O'Connell MJ, et al. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol.; 29(1): 11-6.
110. De Gramont A, Van Cutsem E, Tabernero J, et al. AVANT: Results from a randomized, three-arm multinational phase III study to investigate bevacizumab with either XELOX or FOLFOX4 versus FOLFOX4 alone as adjuvant treatment for colon cancer. ASCO Meeting Abstracts. 2011; 29(4_suppl): 362.
111. Van Cutsem E, Lambrechts D, Prenen H, Jain RK, Carmeliet P. Lessons from the adjuvant bevacizumab trial on colon cancer: what next? J Clin Oncol.; 29(1): 1-4.
112. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346(2): 92-8.
113. Herbst RS, Heymach JV, Lippman SM. Lung cancer. N Engl J Med 2008 Sep 25; 359(13): 1367-80.
114. Johnson DH, Fehrenbacher L, Novotny WF, et al. 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(11): 2184-91.
115. 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(24): 2542-50.
116. Ramalingam SS, Dahlberg SE, Langer CJ, et al. Outcomes for elderly advanced stage non-small cell lung cancer (NSCLC) patients (pts) treated with bevacizumab (B) in combination with carboplatin (C) and paclitaxel (P): Analysis of Eastern Cooperative Oncology Group (ECOG) 4599 study. J Clin Oncol (Meeting Abstracts) 2007 June 20, 2007; 25(18_suppl): 7535.
117. 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(8): 1227-34.
118. Manegold C, von Pawel J, Zatloukal P, et al. Randomised, double-blind multicentre phase III study of bevacizumab in combination with cisplatin and gemcitabine in chemotherapy-naive patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC): BO17704. J Clin Oncol (Meeting Abstracts) 2007 June 20, 2007; 25(18_suppl): LBA7514
119. Gridelli C, Maione P, Rossi A, De Marinis F. The role of bevacizumab in the treatment of non-small cell lung cancer: current indications and future developments. Oncologist 2007; 12(10): 1183-93.
120. Dalsania CJ, Hageboutros A, Harris E, Krieger K, Vora C, Stevenson J. Phase II trial of bevacizumab plus pemetrexed and carboplatin in previously untreated advanced nonsquamous non-small cell lung cancer. J Clin Oncol (Meeting Abstracts) 2007; 25(18_suppl): 18163.
121. Reynolds C, Barrera D, Vu DQ, et al. An open-label, phase II trial of nanoparticle albumin bound paclitaxel (nab-paclitaxel), carboplatin, and bevacizumab in first-line patients with advanced non-squamous non-small cell lung cancer (NSCLC). J Clin Oncol (Meeting Abstracts) 2007, 2007; 25(18_suppl): 7610.
122. William WN, Jr., Kies MS, Fossella FV, et al. Phase II study of bevacizumab in combination with docetaxel and carboplatin in patients with metastatic non-small cell lung cancer (NSCLC). J Clin Oncol (Meeting Abstracts) 2007; 25(18_suppl): 18098.
123. Davila E, Lilenbaum R, Raez L, Seigel L, Tseng J, Graham P. Phase II trial of oxaliplatin and gemcitabine with bevacizumab in first-line advanced non-small cell lung cancer (NSCLC). J Clin Oncol (Meeting Abstracts) 2006; 24(18_suppl): 17009.
124. Waples JM, Auerbach M, Boccia R, Wiggans RG, Steis R, Network GIO. A phase II study of oxaliplatin and pemetrexed plus bevacizumab in advanced non-squamous non-small cell lung cancer. J Clin Oncol (Meeting Abstracts) 2007; 25(18_suppl): 18025.
125. Spigel DR, Hainsworth JD, Yardley DA, et al. Phase II trial of irinotecan, carboplatin, and bevacizumab in patients with extensive-stage small cell lung cancer. J Clin Oncol (Meeting Abstracts) 2007; 25(18_suppl): 18130.
126. Sandler A, Szwaric S, Dowlati A, Moore DF, Jr., Schiller JH. A phase II study of cisplatin (P) plus etoposide (E) plus bevacizumab (B) for previously untreated extensive stage small cell lung cancer (SCLC) (E3501): A trial of the Eastern Cooperative Oncology Group. J Clin Oncol (Meeting Abstracts) 2007; 25(18_suppl): 7564.
127. Ready N, Dudek AZ, Wang XF, Graziano S, Green MR, Vokes EE. CALGB 30306: A phase II study of cisplatin (C), irinotecan (I) and bevacizumab (B) for untreated extensive stage small cell lung cancer (ES-SCLC). J Clin Oncol (Meeting Abstracts) 2007; 25(18_suppl): 7563.
128. Zubkus JD, Spigel DR, Greco FA, et al. Phase II trial of irinotecan, carboplatin, and bevacizumab in patients with limited-stage small cell lung cancer. J Clin Oncol (Meeting Abstracts) 2007; 25(18_suppl): 18133.
129. Ellis LM. Epidermal growth factor receptor in tumor angiogenesis. Hematol Oncol Clin North Am 2004; 18(5): 1007-21, viii.
130. Byers LA, Heymach JV. Dual targeting of the vascular endothelial growth factor and epidermal growth factor receptor pathways: rationale and clinical applications for non-small-cell lung cancer. Clin Lung Cancer 2007; 8 Suppl 2: S79-85.
131. Selvaggi G, Novello S, Torri V, et al. Epidermal growth factor receptor overexpression correlates with a poor prognosis in completely resected non-small-cell lung cancer. Ann Oncol 2004; 15(1): 28-32.
132. Tabernero J. The role of VEGF and EGFR inhibition: implications for combining anti-VEGF and anti-EGFR agents. Mol Cancer Res 2007; 5(3): 203-20.
133. Herbst RS, Johnson DH, Mininberg E, et al. Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer. J Clin Oncol 2005; 23(11): 2544-55.
134. Herbst RS, O'Neill VJ, Fehrenbacher L, et al. Phase II study of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non small-cell lung cancer. J Clin Oncol 2007; 25(30): 4743-50.
135. Lynch TJ, Jr., Blumenschein GR, Jr., Engelman JA, et al. Summary statement novel agents in the treatment of lung cancer: Fifth Cambridge Conference assessing opportunities for combination therapy. J Thorac Oncol 2008; 3(6 Suppl 2): S107-12.
136. Miller KD, Chap LI, Holmes FA, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 2005; 23(4): 792-9.
137. Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007; 357(26): 2666-76.
138. Miles DW, Chan A, Dirix LY, et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol.; 28(20): 3239-47.
139. Robert NJ, Dieras V, Glaspy J, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol.; 29(10): 1252-60.
140. Cobleigh MA, Langmuir VK, Sledge GW, et al. A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 2003; 30(5 Suppl 16): 117-24.
141. Brufsky A, Rivera RR, Hurvitz SA, et al. Progression-free survival (PFS) in patient subgroups in RIBBON-2, a phase III trial of chemotherapy (chemo) plus or minus bevacizumab (BV) for second-line treatment of HER2-negative, locally recurrent or metastatic breast cancer (MBC). ASCO Meeting Abstracts. 2010; 28(15_suppl): 1021.
142. Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med 1996; 335(12): 865-75.
143. Khasawneh MK, Bukowski RM. Pathways of dysregulation in renal cell carcinoma: rational approaches to development of novel treatment. Clin Genitourin Cancer 2006; 5 Suppl 1: S7-S18.
144. 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(9605): 2103-11.
145. Rini BI, Halabi S, Rosenberg JE, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 2008; 26(33): 5422-8.
146. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin.; 60(5): 277-300.
147. Partridge EE, Barnes MN. Epithelial ovarian cancer: prevention, diagnosis, and treatment. CA Cancer J Clin 1999; 49(5): 297-320.
148. Cannistra SA. Cancer of the ovary. N Engl J Med 2004; 351(24): 2519-29.
149. Burger RA, Brady MF, Bookman MA, et al. Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. ASCO Meeting Abstracts. 2010; 28(18_suppl): LBA1.
150. Kristensen G, Perren T, Qian W, et al. Result of interim analysis of overall survival in the GCIG ICON7 phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer. ASCO Meeting Abstracts. 2011; 29(18_suppl): LBA5006.
151. Aghajanian C, Finkler NJ, Rutherford T, et al. OCEANS: A randomized, double-blinded, placebo-controlled phase III trial of chemotherapy with or without bevacizumab (BEV) in patients with platinum-sensitive recurrent epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC). ASCO Meeting Abstracts. 2011; 29(18_suppl): LBA5007.
152. Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med 2008; 359(5): 492-507.
153. Wong ET, Hess KR, Gleason MJ, et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 1999; 17(8): 2572-8.
154. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352(10): 987-96.
155. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005; 352(10): 997-1003.
156. Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009; 10(5): 459-66.
157. Brem S, Cotran R, Folkman J. Tumor angiogenesis: a quantitative method for histologic grading. J Natl Cancer Inst 1972; 48(2): 347-56.
158. Leon SP, Folkerth RD, Black PM. Microvessel density is a prognostic indicator for patients with astroglial brain tumors. Cancer 1996; 77(2): 362-72.
159. Schmidt NO, Westphal M, Hagel C, et al. Levels of vascular endothelial growth factor, hepatocyte growth factor/scatter factor and basic fibroblast growth factor in human gliomas and their relation to angiogenesis. Int J Cancer 1999; 84(1): 10-8.
160. Zhou YH, Tan F, Hess KR, Yung WK. The expression of PAX6, PTEN, vascular endothelial growth factor, and epidermal growth factor receptor in gliomas: relationship to tumor grade and survival. Clin Cancer Res 2003; 9(9): 3369-75.
161. Sathornsumetee S, Reardon DA. Targeting multiple kinases in glioblastoma multiforme. Expert Opin Investig Drugs 2009; 18(3): 277-92.
162. Cohen MH, Shen YL, Keegan P, Pazdur R. FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist 2009; 14(11): 1131-8.
163. Vredenburgh JJ, Desjardins A, Herndon JE, 2nd, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 2007; 25(30): 4722-9.
164. Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2009; 27(28): 4733-40.
165. 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(5): 740-5.
166. O'Farrell AM, Abrams TJ, Yuen HA, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 2003; 101(9): 3597-605.
167. Kim DW, Jo YS, Jung HS, et al. An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases. J Clin Endocrinol Metab 2006; 91(10): 4070-6.
168. Heinrich MC, Blanke CD, Druker BJ, Corless CL. Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol 2002; 20(6): 1692-703.
169. Cockman ME, Masson N, Mole DR, et al. Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein. J Biol Chem 2000; 275(33): 25733-41.
170. Kaelin WG, Jr. The von Hippel-Lindau tumor suppressor gene and kidney cancer. Clin Cancer Res 2004; 10(18 Pt 2): 6290S-5S.
171. Kim WY, Kaelin WG. Role of VHL gene mutation in human cancer. J Clin Oncol 2004; 22(24): 4991-5004.
172. Motzer RJ, 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): 16-24.
173. Motzer RJ, Michaelson MD, Rosenberg J, et al. Sunitinib efficacy against advanced renal cell carcinoma. J Urol 2007; 178(5): 1883-7.
174. Motzer RJ, Hutson TE, Tomczak P, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 2009; 27(22): 3584-90.
175. Gore ME, Szczylik C, Porta C, et al. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol 2009; 10(8): 757-63.
176. Escudier B, Roigas J, Gillessen S, et al. Phase II study of sunitinib administered in a continuous once-daily dosing regimen in patients with cytokine-refractory metastatic renal cell carcinoma. J Clin Oncol 2009; 27(25): 4068-75.
177. Rini BI, Cohen DP, Lu DR, et al. Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst.; 103(9): 763-73.
178. Schmidinger M, Bojic A, Vogl UM, Lamm W, Zielinski CC. Management of cardiac adverse events occurring with sunitinib treatment. Anticancer Res 2009; 29(5): 1627-9.
179. Keizman D, Huang P, Eisenberger MA, et al. Angiotensin system inhibitors and outcome of sunitinib treatment in patients with metastatic renal cell carcinoma: A retrospective examination. Eur J Cancer.; 47(13): 1955-61.
180. Houk BE, Bello CL, Poland B, Rosen LS, Demetri GD, Motzer RJ. Relationship between exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer: results of a pharmacokinetic/pharmacodynamic meta-analysis. Cancer Chemother Pharmacol.; 66(2): 357-71.
181. Rini BI, Tamaskar I, Shaheen P, et al. Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst 2007; 99(1): 81-3.
182. Hirota S, Isozaki K, Nishida T, Kitamura Y. Effects of loss-of-function and gain-of-function mutations of c-kit on the gastrointestinal tract. J Gastroenterol 2000; 35 Suppl 12: 75-9.
183. Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 2003; 299(5607): 708-10.
184. Heinrich MC, Maki RG, Corless CL, et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol 2008; 26(33): 5352-9.
185. Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006; 368(9544): 1329-38.
186. Cohen EE, Needles BM, Cullen KJ, et al. Phase 2 study of sunitinib in refractory thyroid cancer. ASCO Meeting Abstracts 2008; 26(15_suppl): 6025.
187. De Souza JA, Busaidy N, Zimrin A, et al. Phase II trial of sunitinib in medullary thyroid cancer (MTC). ASCO Meeting Abstracts. 2010; 28(15_suppl): 5504.
188. Robert NJ, Saleh MN, Paul D, et al. Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: a phase III, randomized, open-label trial. Clin Breast Cancer.; 11(2): 82-92.
189. Mayer EL, Dhakil S, Patel T, et al. SABRE-B: an evaluation of paclitaxel and bevacizumab with or without sunitinib as first-line treatment of metastatic breast cancer. Ann Oncol.; 21(12): 2370-6.
190. Crown J, Dieras V, Staroslawska E, et al. Phase III trial of sunitinib (SU) in combination with capecitabine (C) versus C in previously treated advanced breast cancer (ABC). ASCO Meeting Abstracts. 2010; 28(18_suppl): LBA1011.
191. Bergh J, Greil R, Voytko N, et al. Sunitinib (SU) in combination with docetaxel (D) versus D alone for the first-line treatment of advanced breast cancer (ABC). ASCO Meeting Abstracts. 2010; 28(18_suppl): LBA1010.
192. 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(4): 650-6.
193. 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(9): 1543-8.
194. Socinski MA, Scappaticci FA, Samant M, Kolb MM, Kozloff MF. Safety and efficacy of combining sunitinib with bevacizumab + paclitaxel/carboplatin in non-small cell lung cancer. J Thorac Oncol.; 5(3): 354-60.
195. O'Mahar SE, Campbell TC, Hoang T, et al. Phase I study of sunitinib and erlotinib in advanced nonsquamous non-small cell lung cancer. J Thorac Oncol.; 6(5): 951-3.
196. 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.; 6(6): 1117-20.
197. Wilhelm S, Carter C, Lynch M, et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov 2006; 5(10): 835-44.
198. Strumberg D, Clark JW, Awada A, et al. Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors. Oncologist 2007; 12(4): 426-37.
199. Escudier B, Eisen T, Stadler WM, et al. Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol 2009; 27(20): 3312-8.
200. Escudier B, Szczylik C, Hutson TE, et al. Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol 2009; 27(8): 1280-9.
201. Beck J, Procopio G, Bajetta E, et al. Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings. Ann Oncol; 22(8): 1812-23.
202. Stadler WM, Figlin RA, McDermott DF, et al. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer; 116(5): 1272-80.
203. Bellmunt J, Fishman M, Eisen T, Quinn D. Expert opinion on the use of first-line sorafenib in selected metastatic renal cell carcinoma patients. Expert Rev Anticancer Ther; 10(6): 825-35.
204. Abou-Alfa GK, Schwartz L, Ricci S, et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2006; 24(26): 4293-300.
205. Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009; 10(1): 25-34.
206. Cheng A, Kang Y, Lin D, et al. Phase III trial of sunitinib (Su) versus sorafenib (So) in advanced hepatocellular carcinoma (HCC). ASCO Meeting Abstracts. 2011; 29(15_suppl): 4000.
207. Kloos RT, Ringel MD, Knopp MV, et al. Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol 2009; 27(10): 1675-84.
208. Gupta-Abramson V, Troxel AB, Nellore A, et al. Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol 2008; 26(29): 4714-9.
209. Madhunapantula SV, Robertson GP. Is B-Raf a good therapeutic target for melanoma and other malignancies? Cancer Res 2008; 68(1): 5-8.
210. Amaravadi RK, Schuchter LM, McDermott DF, et al. Phase II Trial of Temozolomide and Sorafenib in Advanced Melanoma Patients with or without Brain Metastases. Clin Cancer Res 2009; 15(24): 7711-8.
211. Eisen T, Marais R, Affolter A, et al. Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies. Br J Cancer; 105(3): 353-9.
212. Agarwala SS, Keilholz U, Hogg D, et al. Randomized phase III study of paclitaxel plus carboplatin with or without sorafenib as second-line treatment in patients with advanced melanoma. ASCO Meeting Abstracts 2007; 25(18_suppl): 8510.
213. Flaherty KT, Lee SJ, Schuchter LM, et al. Final results of E2603: A double-blind, randomized phase III trial comparing carboplatin (C)/paclitaxel (P) with or without sorafenib (S) in metastatic melanoma. ASCO Meeting Abstracts. 2010; 28(15_suppl): 8511.
214. Harris PA, Boloor A, Cheung M, et al. Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-m ethyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor. J Med Chem 2008; 51(15): 4632-40.
215. 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(6): 1061-8.
216. Slamon D, Gomez HL, Kabbinavar FF, et al. Randomized study of pazopanib + lapatinib vs. lapatinib alone in patients with HER2-positive advanced or metastatic breast cancer. ASCO Meeting Abstracts 2008; 26(15_suppl): 1016.
217. Taylor SK, Chia S, Dent S, et al. A phase II study of pazopanib in patients with recurrent or metastatic invasive breast carcinoma: a trial of the Princess Margaret Hospital phase II consortium. Oncologist; 15(8): 810-8.
218. Bible KC, Suman VJ, Molina JR, et al. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol; 11(10): 962-72.
219. Verheul HM, Pinedo HM. Possible molecular mechanisms involved in the toxicity of angiogenesis inhibition. Nat Rev Cancer 2007; 7(6): 475-85.
220. Zhu X, Wu S, Dahut WL, Parikh CR. Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis. Am J Kidney Dis 2007; 49(2): 186-93.
221. van Heeckeren WJ, Ortiz J, Cooney MM, Remick SC. Hypertension, proteinuria, and antagonism of vascular endothelial growth factor signaling: clinical toxicity, therapeutic target, or novel biomarker? J Clin Oncol 2007; 25(21): 2993-5.
222. Eremina V, Jefferson JA, Kowalewska J, et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008; 358(11): 1129-36.
223. Kappers MH, van Esch JH, Sluiter W, Sleijfer S, Danser AH, van den Meiracker AH. Hypertension induced by the tyrosine kinase inhibitor sunitinib is associated with increased circulating endothelin-1 levels. Hypertension; 56(4): 675-81.
224. Kappers MH, Smedts FM, Horn T, et al. The vascular endothelial growth factor receptor inhibitor sunitinib causes a preeclampsia-like syndrome with activation of the endothelin system. Hypertension; 58(2): 295-302.
225. Kamba T, McDonald DM. Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer 2007; 96(12): 1788-95.
226. Feliers D, Chen X, Akis N, Choudhury GG, Madaio M, Kasinath BS. VEGF regulation of endothelial nitric oxide synthase in glomerular endothelial cells. Kidney Int 2005; 68(4): 1648-59.
227. Hood JD, Meininger CJ, Ziche M, Granger HJ. VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am J Physiol 1998; 274(3 Pt 2): H1054-8.
228. Horowitz JR, Rivard A, van der Zee R, et al. Vascular endothelial growth factor/vascular permeability factor produces nitric oxide-dependent hypotension. Evidence for a maintenance role in quiescent adult endothelium. Arterioscler Thromb Vasc Biol 1997; 17(11): 2793-800.
229. Scappaticci FA, Skillings JR, Holden SN, et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 2007; 99(16): 1232-9.
230. Scappaticci FA, Fehrenbacher L, Cartwright T, et al. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 2005; 91(3): 173-80.
231. Chen HX, Cleck JN. Adverse effects of anticancer agents that target the VEGF pathway. Nat Rev Clin Oncol 2009; 6(8): 465-77.
232. Traina TA, Norton L, Drucker K, Singh B. Nasal septum perforation in a bevacizumab-treated patient with metastatic breast cancer. Oncologist 2006; 11(10): 1070-1.
233. Ozcan C, Wong SJ, Hari P. Reversible posterior leukoence-phalopathy syndrome and bevacizumab. N Engl J Med 2006; 354(9): 980-2; discussion -2.
234. Estilo CL, Fornier M, Farooki A, Carlson D, Bohle G, 3rd, Huryn JM. Osteonecrosis of the jaw related to bevacizumab. J Clin Oncol 2008; 26(24): 4037-8.
235. Roodhart JM, Langenberg MH, Witteveen E, Voest EE. The molecular basis of class side effects due to treatment with inhibitors of the VEGF/VEGFR pathway. Curr Clin Pharmacol 2008; 3(2): 132-43.
236. Je Y, Schutz FA, Choueiri TK. Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. Lancet Oncol 2009; 10(10): 967-74.
237. Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 2008; 8(8): 592-603.
238. Miller KD, Sweeney CJ, Sledge GW, Jr. The Snark is a Boojum: the continuing problem of drug resistance in the antiangiogenic era. Ann Oncol 2003; 14(1): 20-8.
239. Autiero M, Waltenberger J, Communi D, et al. Role of PlGF in the intra-and intermolecular cross talk between the VEGF receptors Flt1 and Flk1. Nat Med 2003; 9(7): 936-43.
240. Adini A, Kornaga T, Firoozbakht F, Benjamin LE. Placental growth factor is a survival factor for tumor endothelial cells and macrophages. Cancer Res 2002; 62(10): 2749-52.
241. Yan M, Plowman GD. Delta-like 4/Notch signaling and its therapeutic implications. Clin Cancer Res 2007; 13(24): 7243-6.
242. Casanovas O, Hicklin DJ, Bergers G, Hanahan D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 2005; 8(4): 299-309.
243. Mizukami Y, Jo WS, Duerr EM, et al. Induction of interleukin-8 preserves the angiogenic response in HIF-1alpha-deficient colon cancer cells. Nat Med 2005; 11(9): 992-7.
244. Teodoro JG, Evans SK, Green MR. Inhibition of tumor angiogenesis by p53: a new role for the guardian of the genome. J Mol Med (Berl) 2007; 85(11): 1175-86.
245. Schneider BP, Wang M, Radovich M, et al. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol 2008; 26(28): 4672-8.
246. Schultheis AM, Lurje G, Rhodes KE, et al. Polymorphisms and clinical outcome in recurrent ovarian cancer treated with cyclophosphamide and bevacizumab. Clin Cancer Res 2008; 14(22): 7554-63.
247. Crawford Y, Kasman I, Yu L, et al. PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. Cancer Cell 2009; 15(1): 21-34.
248. Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 2006; 124(2): 263-6.
249. Shojaei F, Singh M, Thompson JD, Ferrara N. Role of Bv8 in neutrophil-dependent angiogenesis in a transgenic model of cancer progression. Proc Natl Acad Sci USA 2008; 105(7): 2640-5.
250. Batchelor TT, Sorensen AG, di Tomaso E, et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 2007; 11(1): 83-95.
251. Allen E, Walters IB, Hanahan D. Brivanib, a dual FGF/VEGF inhibitor, is active both first and second line against mouse pancreatic neuroendocrine tumors developing adaptive/evasive resistance to VEGF inhibition. Clin Cancer Res; 17(16): 5299-310.
252. Fischer C, Mazzone M, Jonckx B, Carmeliet P. FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy? Nat Rev Cancer 2008; 8(12): 942-56.
253. Yang L, DeBusk LM, Fukuda K, et al. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 2004; 6(4): 409-21.
254. Pan Q, Chanthery Y, Liang WC, et al. Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell 2007; 11(1): 53-67.
255. Loges S, Schmidt T, Carmeliet P. Mechanisms of resistance to anti-angiogenic therapy and development of third-generation anti-angiogenic drug candidates. Genes Cancer; 1(1): 12-25.
256. Brower V. Antiangiogenesis research is booming, as questions and studies proliferate. J Natl Cancer Inst 2009; 101(11): 780-1.
257. Bhatt RS, Seth P, Sukhatme VP. Biomarkers for monitoring antiangiogenic therapy. Clin Cancer Res 2007; 13(2 Pt 2): 777s-80s.