Role of angiogenesis inhibitors in colorectal cancer: Sensitive and insensitive tumors

Current Cancer Drug Targets

Volumn 12, Issue 4, 2012, Pages 303-315

  Bagnasco, L ^a,b   Piras, D ^a   Parodi, S ^a,b   Bauer, I ^a   Zoppoli, G ^a   Patrone, F ^a   Ballestrero, A ^a  

^a UNIVERSITY OF GENOA   (Italy)

^b UNIVERSITY OF GENOA   (Italy)

Author keywords

Angiogenesis inhibitors; Bevacizumab; Colorectal cancer; Metastasis; Neo angiogenesis; VEGF receptor family

Indexed keywords

AFLIBERCEPT; ANGIOGENESIS INHIBITOR; BEVACIZUMAB; CAPECITABINE; CEDIRANIB; CETUXIMAB; FLUOROURACIL; FOLINIC ACID; IMATINIB; IRINOTECAN; IXABEPILONE; LENALIDOMIDE; OXALIPLATIN; PANITUMUMAB; PAZOPANIB; PLACENTA GROWTH FACTOR 2; PLACENTAL GROWTH FACTOR; PLACENTAL GROWTH FACTOR 1; RAMUCIRUMAB; REGORAFENIB; SORAFENIB; SUNITINIB; THALIDOMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANDETANIB; VASCULOTROPIN A; VASCULOTROPIN B; VASCULOTROPIN C; VASCULOTROPIN D; VASCULOTROPIN E; ZALTRAP;

ANGIOGENESIS; ANTIANGIOGENIC THERAPY; CLINICAL FEATURE; COLORECTAL CANCER; CONGESTIVE HEART FAILURE; DIGESTIVE SYSTEM PERFORATION; HUMAN; HYPERTENSION; HYPOXIA; MEDICAL LITERATURE; NEPHROTIC SYNDROME; ONCOLOGY; PROTEINURIA; REVIEW; THROMBOEMBOLISM; VASCULARIZATION; WOUND HEALING;

ADENOMATOUS POLYPOSIS COLI; ANGIOGENESIS INHIBITORS; ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; COLORECTAL NEOPLASMS; FEMALE; HUMANS; MALE; MICE; NEOVASCULARIZATION, PATHOLOGIC; TREATMENT OUTCOME; TUMOR MARKERS, BIOLOGICAL; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84860278780     PISSN: 15680096     EISSN: 18735576     Source Type: Journal    
DOI: 10.2174/156800912800190929     Document Type: Review

References (145)

1. Facts, C. Cancer Facts & Figures Health Policy 2010.
2. Rustgi, A. K. The genetics of hereditary colon cancer. Genes Dev. 2007, 21 (20), 2525-2538.
3. Dekker, N.; Hermens, R. P.; Elwyn, G.; Weijden, T. van der; Nagengast, F. M.; Duijvendijk, P. van; Salemink, S.; Adang, E.; Krieken, J. H. J. van; Ligtenberg, M. J.; Hoogerbrugge, N. Improving calculation, interpretation and communication of familial colorectal cancer risk: Protocol for a randomized controlled trial. Implement Sci. 2010, 5 (1), 6.
4. Jemal, A.; Siegel, R.; Ward, E.; Hao, Y.; Xu, J.; Murray, T.; Thun, M. J. Cancer statistics, 2008. CA Cancer J. Clin. 2011, 58 (2), 71-96.
5. Imperiale, T. F.; Wagner, D. R.; Lin, C. Y.; Larkin, G. N.; Rogge, J. D.; Ransohoff, D. F. Results of screening colonoscopy among persons 40 to 49 years of age. N. Engl. J. Med 2002, 346 (23), 1781-1785.
6. Abbas, S.; Lam, V.; Hollands, M. Ten-year survival after liver resection for colorectal metastases: systematic review and metaanalysis. ISRN Oncol. 2011; 2011:763245.
7. Labianca, R.; Beretta, G. D.; Kildani, B.; Milesi, L.; Merlin, F.; Mosconi, S.; Pessi, M. A.; Prochilo, T.; Quadri, A.; Gatta, G.; Braud, F. de; Wils, J. Colon cancer. Crit. Rev. Oncol. Hematol. 2010, 742, 106-133.
8. Penna, C.; Nordlinger, B. Colorectal metastasis (liver and lung). The Surgical clinics of North America 2002, 82 (5), 1075-1090, 23.
9. Fong, Y.; Brennan, M. F.; Cohen, A. M.; Heffernan, N.; Freiman, A.; Blumgart, L. H. Liver resection in the elderly. Br. J. Surg. 1997, 84 (10), 1386-1390.
10. Eadens, M. J.; Grothey, A. Curable metastatic colorectal cancer. Curr. Oncol. Rep. 2011, 13 (3), 168-176.
11. Tol, J.; Punt, C. J. Monoclonal antibodies in the treatment of metastatic colorectal cancer: a review. Clin. Ther. 2010, 32 (3), 437-453.
12. Takahashi, Y.; Kitadai, Y.; Bucana, C. D.; Cleary, K. R.; Ellis, L. M. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res. 1995, 55 (18), 3964-3968.
13. Luttun, A.; Tjwa, M.; Moons, L.; Wu, Y.; Angelillo-Scherrer, A.; Liao, F.; Nagy, J. A.; Hooper, A.; Priller, J.; De Klerck, B.; Compernolle, V.; Daci, E.; Bohlen, P.; Dewerchin, M.; Herbert, J.- M.; Fava, R.; Matthys, P.; Carmeliet, G.; Collen, D.; Dvorak, H. F.; Hicklin, D. J.; Carmeliet, P. Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat. Med. 2002, 8 (8), 831-840.
14. Folkman, J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 1971, 285 (21), 1182-1186.
15. Arnold, D.; Seufferlein, T. Targeted treatments in colorectal cancer: state of the art and future perspectives. Gut 2010, 59 (6), 838-858.
16. Dvorak, H. F. Vascular permeability factor/vascular endothelial growth factor: A critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J. Clin. Oncol. 2002, 20 (21), 4368-4380.
17. Dvorak, H. F.; Brown, L. F.; Detmar, M.; Dvorak, A. M. Vascular Permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am. J. Pathol. 1995, 146 (5), 1029-1039.
18. Zachary, I. Signaling mechanisms mediating vascular protective actions of vascular endothelial growth factor. Am. J. Physiol., Cell Physiol. 2001, 280 (6), C1375-1386.
19. Bates, D. Regulation of vascular permeability by vascular endothelial growth factors. Vascul. Pharmacol. 2002, 39 (4-5), 225-237.
20. Gerber, H. P.; McMurtrey, A.; Kowalski, J.; Yan, M.; Keyt, B. A.; Dixit, V.; Ferrara, N. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J. Biol. Chem. 1998, 273 (46), 30336-30343.
21. Gerber, H. P.; Dixit, V.; Ferrara, N. Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J. Biol. Chem. 1998, 273 (21), 13313-13316.
22. Thakker, G. D.; Hajjar, D. P.; Muller, W. A.; Rosengart, T. K. The role of phosphatidylinositol 3-kinase in vascular endothelial growth factor signaling. J. Biol. Chem. 1999, 274 (15), 10002-10007.
23. Hicklin, D. J.; Ellis, L. M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J. Clin. Oncol. 2005, 23 (5), 1011-1027.
24. Ferrara, N.; Gerber, H. P.; Le Couter, J. The biology of VEGF and its receptors. Nat. Med. 2003, 9 (6), 669-676.
25. Houck, K. A.; Ferrara, N.; Winer, J.; 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 (12), 1806-1814.
26. Leung, D. W.; Cachianes, G.; Kuang, W. J.; Goeddel, D. V.; Ferrara, N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989, 246 (4935), 1306-1309.
27. Keck, P. J.; Hauser, S. D.; Krivi, G.; Sanzo, K.; Warren, T.; Feder, J.; Connolly, D. T. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 1989, 246 (4935), 1309-1312.
28. Murphy, J. F.; Fitzgerald, D. J. Vascular endothelial cell growth factor (VEGF) induces cyclooxygenase (COX)-dependent proliferation of endothelial cells (EC) via the VEGF-2 receptor. FASEB J. 2001, 15 (9), 1667-1669
29. Woolard, J.; Wang, W. Y.; Bevan, H. S.; Qiu, Y.; Morbidelli, L.; Pritchard-Jones, R. O.; Cui, T. G.; Sugiono, M.; Waine, E.; Perrin, R.; Foster, R.; Digby-Bell, J.; Shields, J. D.; Whittles, C. E.; Mushens, R. E.; Gillatt, D. A.; Ziche, M.; Harper, S. J.; Bates, D. O. VEGF 165b, an inhibitory vascular endothelial growth factor splice variant: mechanism of action, in vivo effect on angiogenesis and endogenous protein expression. Cancer Res. 2004, 7822-7835.
30. Carmeliet, P.; Ferreira, V.; Breier, G.; Pollefeyt, S.; Kieckens, L.; Gertsenstein, M.; Fahrig, M.; Vandenhoeck, A.; Harpal, K.; Eberhardt, C.; Declercq, C.; Pawling, J.; Moons, L.; Collen, D.; Risau, W.; Nagy, A. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996, 380 (6573), 435-439.
31. Brown, L. F.; Yeo, K. T.; Berse, B.; Morgentaler, A.; Dvorak, H.F.; Rosen, S. Vascular permeability factor (vascular endothelial growth factor) is strongly expressed in the normal male genital tract and is present in substantial quantities in semen. J. Urol. 1995, 154, 576-579.
32. Tischer, E.; Mitchell, R.; Hartman, T.; Silva, M.; Gospodarowicz, D.; Fiddes, J. C.; Abraham, J. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J. Biol. Chem. 1991, 266 (18), 11947-11954.
33. Hiratsuka, S.; Maru, Y.; Okada, A.; Seiki, M.; Noda, T.; Shibuya, M. Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis. Cancer Res. 2001, 61, 1207-1213.
34. Achen, M. G.; Williams, R. A.; Minekus, M. P.; Thornton, G. E.; Stenvers, K.; Rogers, P.; Lederman, F.; Roufail, S.; Stacker, S. Localization of vascular endothelial growth factor-D in malignant melanoma suggests a role in tumour angiogenesis. J. Pathol. 2001, 193 (2), 147-154.
35. Valtola, R.; Salven, P.; Heikkilä, P.; Taipale, J.; Joensuu, H.; Rehn, M.; Pihlajaniemi, T.; Weich, H.; deWaal, R.; Alitalo, K. VEGFR-3 and its ligand VEGF-C are associated with angiogenesis in breast cancer. Am. J. Pathol. 1999, 154 (5), 1381-1390.
36. Rafii, S.; Lyden, D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat. Med. 2003, 9 (6), 702-712.
37. Asahara, T. Isolation of putative progenitor endothelial cells for Angiogenesis. Science 1997, 275 (5302), 964-966.
38. Garcia-Barros, M.; Paris, F.; Cordon-Cardo, C.; Lyden, D.; Rafii, S.; Haimovitz-Friedman, A.; Fuks, Z.; Kolesnick, R. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science 2003, 300 (5622), 1155-1159.
39. De Palma, M.; Venneri, M. A.; Roca, C.; Naldini, L. Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells. Nat. Med. 2003, 9 (6), 789-795.
40. Göthert, J. R.; Gustin, S. E.; van Eekelen, J. A. M.; Schmidt, U.; Hall, M. A.; Jane, S. M.; Green, A. R.; Göttgens, B.; Izon, D. J.; Begley, C. G. Genetically tagging endothelial cells in vivo: bone marrow-derived cells do not contribute to tumor endothelium. Blood 2004, 104 (6), 1769-1777.
41. Maxwell, P. H.; Wiesener, M. S.; Chang, G. W.; Clifford, S. C.; Vaux, E. C.; Cockman, M. E.; Wykoff, C. C.; Pugh, C. W.; Maher, E. R.; Ratcliffe, P. J. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 1999, 399 (6733), 271-275.
42. Maxwell, P. H.; Ratcliffe, P. J. Oxygen sensors and angiogenesis. Semin. Cell Dev. Biol. 2002, 13 (1), 29-37.
43. Warren, R. S.; Yuan, H.; Matli, M. R.; Ferrara, N.; Donner, D. B. Induction of vascular endothelial growth factor by insulin-like growth factor 1 in colorectal carcinoma. J. Biol. Chem. 1996, 271 (46), 29483-29488.
44. Cao, R.; Bråkenhielm, E.; Li, X.; Pietras, K.; Widenfalk, J.; Ostman, A.; Eriksson, U.; Cao, Y. Angiogenesis stimulated by PDGF-CC, a novel member in the PDGF family, involves activation of PDGFR-alpha-alpha and -alpha-beta receptors. FASEB J. 2002, 16 (12), 1575-1583.
45. Dong, J.; Grunstein, J.; Tejada, M.; Peale, F.; Frantz, G.; Liang, W.-C.; Bai, W.; Yu, L.; Kowalski, J.; Liang, X.; Fuh, G.; Gerber, H.-P.; Ferrara, N. VEGF-null cells require PDGFR alpha signalingmediated stromal fibroblast recruitment for tumorigenesis. EMBO J. 2004, 23 (14), 2800-2810.
46. Ciardiello, F.; Bianco, R.; Damiano, V.; Fontanini, G.; Caputo, R.; Pomatico, G.; Placido, S. D.; Raffaele, A. Antiangiogenic and antitumor activity of anti-epidermal growth factor receptor C225 monoclonal antibody in combination with vascular endothelial growth factor antisense oligonucleotide in human GEO colon cancer cells antiangiogenic and antitumor activity. Clin. Cancer Res. 2000, 6, 3739-3747.
47. Akagi, M.; Kawaguchi, M.; Liu, W.; McCarty, M. F.; Takeda,A.; Fan, F.; Stoeltzing, O.; Parikh, A. A.; Jung, Y. D.; Bucana, C. D.; Mansfield, P. F.; Hicklin, D. J.; Ellis, L. M. Induction of neuropilin-1 and vascular endothelial growth factor by epidermal growth factor in human gastric cancer cells. Br. J. Cancer 2003, 88 (5), 796-802.
48. Yang, W.; Klos, K.; Yang, Y.; Smith, T. L.; Shi, D.; Yu, D. ErbB2 overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human breast carcinoma. Cancer 2002, 94 (11), 2855-2861.
49. Eller, J. L.; Longo, S. L.; Hicklin, D. J.; Canute, G. W. Activity of anti-epidermal growth factor receptor monoclonal antibody C225 against glioblastoma multiforme. Neurosurgery 2002, 51 (4), 1005-1014.
50. Kedar, D.; Baker, C. H.; Killion, J. J.; Dinney, C. P. N.; Fidler, I. J. Blockade of the epidermal growth factor receptor signaling inhibits angiogenesis leading to regression of human renal cell carcinoma growing orthotopically in nude mice. Clin. Cancer Res. 2002, 8, 3592-3600.
51. Goodwin, R. A.; Asmis, T. R. Overview of systemic therapy for colorectal cancer. Clinics 2009, 1 (212), 251-256.
52. National Cancer Institute: Surveillance Epidemiology and End Results. Survival & Stage. http://seer.cancer.gov/statfacts/html/colorect.html#survivalSurvival.
53. Saif, M. W. Targeted agents for adjuvant therapy of colon cancer. Clin. Colorectal Cancer 2006, 6 (1), 46-51.
54. Macarulla, T.; Ramos, F. J.; Elez, E.; Capdevila, J.; Peralta, S.; Tabernero, J. Update on novel strategies to optimize cetuximab therapy in patients with metastatic colorectal cancer. Clin. Colorectal Cancer 2008, 7 (5), 300-308.
55. Benson, A. B. Epidemiology, disease progression, and economic burden of colorectal cancer. J. Manag. Care Pharm: JMCP 2007, 13 (6 Suppl C), S5-18.
56. Wolmark, N.; Fisher, B.; Rockette, H.; Redmond, C.; Wickerham, D. L.; Fisher, E. R.; Jones, J.; Glass,A.; Lerner, H.; Lawrence, W. Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-01. J. Natl. Cancer Inst. 1988, 80 (1), 30-36.
57. Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. Advanced Colorectal Cancer Meta-Analysis Project. J. Clin. Oncol. 1992, 10 (6), 896-903.
58. Laurie, J. A.; Moertel, C. G.; Fleming, T. R.; Wieand, H. S.; Leigh, J. E.; Rubin, J.; McCormack, G. W.; Gerstner, J. B.; Krook, J. E.; Malliard, J.; Twito, D. I.; Morton, R. F.; Tschetter, L. K.; Barlow, J. F. Surgical adjuvant therapy of large-bowel carcinoma: An evaluation of levamisole and the combination of levamisole and fluorouracil. J. Clin. Oncol. 1989, 7 (10), 1447-1456.
59. O'Connell, M. J.; Mailliard, J. A.; Kahn, M. J.; Macdonald, J. S.; Haller, D. G.; Mayer, R. J.; Wiehand, H. S. Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J. Clin. Oncol. 1997, 15 (1), 246-250.
60. Wolmark, N.; Rockette, H.; Fisher, B.; Wickerham, D. L.; Redmond, C.; Fisher, E. R.; Jones, J.; Mamounas, E. P.; Ore, L.; Petrelli, N. J. The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03. J. Clin. Oncol. 1993, 11 (10), 1879-1887.
61. Francini, G.; Petrioli, R.; Lorenzini, L.; Mancini, S.; Armenio, S.; Tanzini, G.; Marsili, S.; Aquino, A.; Marzocca, G.; Civitelli, S. Folinic acid and 5-fluorouracil as adjuvant chemotherapy in colon cancer. Gastroenterology 1994, 106 (4), 899-906.
62. Wolmark, B. N.; Rockette, H.; Mamounas, E.; Jones, J.; Wieand, S.; Wickerham, D. L.; Bear, H. D.; Atkins, J. N.; Dimitrov, N. V.; Glass, A. G.; Fisher, E. R.; Fisher, B. Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes' B and C carcinoma of the colon: Results From National Surgical Adjuvant Breast and Bowel Project C-04. J. Clin. Oncol. 1999, 17 (11), 3553-3559.
63. Scheithauer, W.; Rosen, H.; Kornek, G. V.; Sebesta, C.; Depisch, D. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. Br. Med. J. 1993, 306 (6880), 752-755.
64. Díaz-Rubio, E.; Tabernero, J.; Gómez-España, A.; Massutí, B.; Sastre, J.; Chaves, M.; Abad, A.; Carrato A.; Queralt, B.; Reina, J. J.; Maurel, J.; González-Flores, E.; Aparicio, J.; Rivera, F.; Losa, F.; Aranda, E. Phase III study of capecitabine plus oxaliplatin compared with continuous-infusion fluorouracil plus oxaliplatin as first-line therapy in metastatic colorectal cancer: final report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial. J. Clin. Oncol. 2007, 25 (27), 4224-4230.
65. Porschen, R.; Arkenau, H. T.; Kubicka, S.; Greil, R.; Seufferlein, T.; Freier, W.; Kretzschmar, A.; Graeven, U.; Grothey, A.; Hinke, A.; Schmiegel, W.; Shmoll, H. J. Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J. Clin. Oncol. 2007, 25 (27), 4217-4223.
66. Punt, C. J. A. New options and old dilemmas in the treatment of patients with advanced colorectal cancer. Ann. Oncol. 2004, 15 (10), 1453-1459.
67. Koopman, M.; Punt, C. J. A. Chemotherapy, which drugs and when. Eur. J. Cancer 2009, 45 Suppl 150-156.
68. Amado, R. G.; Wolf, M.; Peeters, M.; Van Cutsem, E.; Siena, S.; Freeman, D. J.; Juan, T.; Sikorski, R.; Suggs, S.; Radinsky, R.; Patterson, S. D.; Chang, D. D. Wild-Type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J. Clin. Oncol. 2008, 26 (10), 1626-1634.
69. Peeters, M.; Price, T.; Van Laethem, J.-L. Anti-epidermal growth factor receptor monotherapy in the treatment of metastatic colorectal cancer: where are we today? Oncologist 2009, 14 (1), 29-39.
70. Bokemeyer, C.; Bondarenko, I.; Hartmann, J. T.; Braud, F. G. D.; Volovat, C. KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without cetuximab: The OPUS experience. J Clin. Oncol. 2008, 26 (15), 4000-4001.
71. Folkman, J. Antiangiogenesis in cancer therapy - endostatin and its mechanisms of action. Exp. Cell Res. 2006, 312 (5), 594-607.
72. Chase, J. L. Clinical use of anti-vascular endothelial growth factor monoclonal antibodies in metastatic colorectal cancer. Pharmacotherapy 2008, 28 (11 Pt 2), 23S-30S.
73. Klümpen, H. J.; Beijnen, J. H.; Gurney, H.; SChellens, J. H. Inhibitors of mTOR. Oncologist 2010, 15 (12), 1262-1269.
74. Gentile, M.; Recchia, A. G.; Vigna, E.; Mazzone, C.; Lucia, E.; Gigliotti, V.; Bossio, S.; Madeo, A.; Morabito, L.; Servillo, P.; Franzese, S.; Caruso, N.; De Stefano, L.; Bisconte, M. G.; Gentile, C.; Morabito, F. Lenalidomide in the treatment of chronic lymphocytic leukemia. Expert Opin. Investig. drugs 2011, 20 (2), 273-286.
75. Bevacizumab. Anti-VEGF monoclonal antibody, avastin, rhumab- VEGF. Drugs R D 2002, 3 (1), 28-30.
76. Aflibercept: AVE 0005, AVE 005, AVE0005, VEGF Trap - Regeneron, VEGF Trap (R1R2), VEGF Trap-Eye. Drugs R D 2008, 9 (4), 261-269.
77. Mulder, K.; Scarfe, A.; Chua, N.; Spratlin, J. The role of bevacizumab in colorectal cancer: understanding its benefits and limitations. Expert Opin. Biol. Ther. 2011, 11 (3), 405-413.
78. Hood, J. D.; Cheresh, D. A Building a better Trap. Proc. Natl. Acad. Sci. U.S.A 2003, 100 (15), 8624-862
79. GEN: Genetic Engineering and biotechnology News: Regeneron and Sanofi-Aventis Report Positive Phase III mCRC Trial Data. http://www.genengnews.com/gen-news-highlights/regeneron-andsanofi-aventis-report-positive-phase-iii-mcrc-trial-data/81245067/
80. Hurwitz, H.; Fehrenbacher, L.; Novotny, W.; Cartwright, T.; Hainsworth, J.; Heim, W.; Berlin, J.; Baron, A.; Griffing, S.; Holmgren, E.; Ferrara, N.; Fyfe, G.; Rogers, B.; Ross, R.; Kabbinavar, F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer N. Engl. J. Med 2004, 350 (23), 2335-2342.
81. Giantonio, B. J.; Catalano, P. J.; Meropol, N. J.; O'Dwyer, P. J.; Mitchell, E. P.; Alberts, S. R.; Schwartz, M. A.; Benson, A. B. 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), 1539-1544.
82. Van Cutsem, E.; Labianca, R.; Bodoky, G.; Barone, C.; Aranda, E.; Nordlinger, B.; Topham, C.; Tabernero, J.; André, T.; Sobrero, A. F.; Mini, E.; Greil, R.; Di Costanzo, F.; Collette, L.; Cisar, L.; Zhang, X.; Khayat, D.; Bokemeyer, C.; Roth, A. D.; Cunningham, D. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J. Clin. Oncol. 2009, 27 (19), 3117-25.
83. Van Cutsem, E.; Lambrechts, D.; Prenen, H.; Jain, R. K.; Carmeliet, P. Lessons from the adjuvant bevacizumab trial on colon cancer: what next? J. Clin. Oncol. 2011, 29 (1), 1-4.
84. Pàez-Ribes, M.; Allen, E.; Hudock, J.; Takeda, T.; Okuyama, H.; Viñals, F.; Inoue, M.; Bergers, G.; Hanahan, D. Casanovas, O. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 2009, 15 (3), 220-231.
85. Ebos, J. M. L.; Lee, C. R.; Cruz-Munoz, W.; Bjarnason, G.A.; Christensen, J. G.; Kerbel, R. S. Accelerated metastasis after shortterm treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 2009, 15 (3), 232-239.
86. Mancuso, M. R.; Davis, R.; Norberg, S. M.; O'Brien, S.; Sennino, B.; Nakahara, T.; Yao, V. J.; Inai, T.; Brooks, P.; Freimark, B.; Shalinsky, D. R.; Hu-Lowe, D. D.; McDonald, D. M. Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J. Clin. Invest. 2006, 116 (10).
87. Vredenburgh, J. J.; Desjardins, A.; Herndon, J. E.; Marcello, J.; Reardon, D.A.; Quinn, J.A.; Rich, J. N.; Sathornsumetee, S.; Gururangan, S.; Sampson, J.; Wagner, M.; Bailey, L.; Bigner, D. D.; Friedman, A. H.; Friedman, H. S. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J. Clin. Oncol. 2007, 25 (30), 4722-4729.
88. Mrugala, M. M. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology 2009, 72 (8), 773-774.
89. Miles, D.; Harbeck, N.; Escudier, B.; Hurwitz, H.; Saltz, L.; Van Cutsem, E.; Cassidy, J.; Mueller, B.; Sirzén, F. Disease course patterns after discontinuation of bevacizumab: pooled analysis of randomized phase III trials. J. Clin. Oncol. 2011, 29 (1), 83-88.
90. Grothey, A.; Sugrue, M. M.; Purdie, D. M.; Dong, W.; Sargent, D.; Hedrick, E.; Kozloff, M. Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). J. Clin. Oncol. 2008, 26 (33), 5326-5334.
91. Ellis, L. M.; Reardon, D. A. Is there really a yin and yang to VEGF-targeted therapies? The lancet oncology 2010, 11 (9), 809-811.
92. Allegra, C. J.; Yothers, G.; O'Connell, M. J.; Sharif, S.; Petrelli, N. J.; Colangelo, L. H.; Atkins, J. N.; Seay, T. E.; Fehrenbacher, L.; Goldberg, R. M.; O'Reilly, S.; Chu, L.; Azar, C. A.; Lopa, S.; Wolmark, N. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J. Clin. Oncol. 2011, 29 (1), 11-16.
93. Andre, T.; Cutsem, E. V.; Schmoll, H.; Tabernero, J.; Clarke, S.; Moore, M. J.; Cunningham, D.; Cartwright, T. H.; Hecht, J. R.; Rivera, F.; Im, S.; Bodoky, G.; Salazar, R.; Shmueli, E. A multinational, randomized phase III study of bevacizumab (Bev) with FOLFOX4 or XELOX versus FOLFOX4 alone as adjuvant treatment for colon cancer (CC): Subgroup analyses from the AVANT trial. J. Clin. Oncol. 2011, 29, 3509.
94. Gruenberger, B.; Tamandl, D.; Schueller, J.; Scheithauer, W.; Zielinski, C.; Herbst, F.; Gruenberger, T. Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J. Clin. Oncol. 2008, 26 (11), 1830-1835.
95. Schrag, D.; Weiser, M. R.; Goodman, K. A.; Gonen, M.; Cercek, A.; Reidy, D. L.; Temple, L. K.; Wong, W. D.; Paty, P.; Saltz, L. Neoadjuvant FOLFOX-bev, without radiation, for locally advanced rectal cancer. J. Clin. Oncol. 2010, 28 (15), 3511.
96. Hoehler, T.; Dellas, K.; Riesenbeck, D.; Reese, T.; Wuerschmidt, F.; Roedel, C.; Wagner, W.; Zuehlke, H. Preoperative chemoradiation (CRT) with concurrent capecitabine (Cap), oxaliplatin (Ox), and bevacizumab (Bev) in patients with locally advanced rectal cancer (RC): Effects on pathological complete response (pCR) and surgical complications. J. Clin. Oncol. 2011, 29 (suppl; abstr 3630).
97. O'Brien, S. G.; Guilhot, F.; Larson, R.A.; Gathmann, I.; Baccarani, M.; Cervantes, F.; Cornelissen, J. J.; Fischer, T.; Hochhaus, A.; Hughes, T.; Lechner, K.; Nielsen, J. L.; Rousselot, P.; Reiffers, J.; Saglio, G.; Shepherd, J.; Simonsson, B.; Gratwohl, A.; Goldman, J. M.; Kantarjian, H.; Taylor, K.; Verhoef, G.; Bolton, A. E.; Capdeville, R.; Druker, B. J. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N. Engl. J. Med 2003, 348 (11), 994-1004.
98. Fabian, M.A.; Biggs, W. H.; Treiber, D. K.; Atteridge, C. E.; Azimioara, M. D.; Benedetti, M. G.; Carter, T.A.; Ciceri, P.; Edeen, P. T.; Floyd, M.; Ford, J. M.; Galvin, M.; Gerlach, J. L.; Grotzfeld, R. M.; Herrgard, S.; Insko, D. E.; Insko, M.A.; Lai, A. G.; Lélias, J.-M.; Mehta, S.A.; Milanov, Z. V.; Velasco, A. M.; Wodicka, L. M.; Patel, H. K.; Zarrinkar, P. P.; Lockhart, D. J. A small moleculekinase interaction map for clinical kinase inhibitors. Nat. Biotechnol. 2005, 23 (3), 329-336.
99. NCBI: PubChem Compound. http://www.ncbi.nlm.nih.gov/pccompound.
100. 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. P.; 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 (10), 4389-4400.
101. Hennequin, L. F.; Stokes, E. S. E.; Thomas, A. P.; Johnstone, C.; Plé, P.A.; Ogilvie, D. J.; Dukes, M.; Wedge, S. R.; Kendrew, J.; Curwen, J. O. Novel 4-anilinoquinazolines with C-7 basic side chains: design and structure activity relationship of a series of potent, orally active, VEGF receptor tyrosine kinase inhibitors. J. Med. Chem. 2002, 45 (6), 1300-1312.
102. Sun, L.; Liang, C.; Shirazian, S.; Zhou, Y.; Miller, T.; Cui, J.; Fukuda, J. Y.; Chu, J.-yu; Nematalla, A.; Wang, X.; Chen, H.; Sistla, A.; Luu, T. C.; Tang, F. Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase. J. Med. Chem. 2003, 46 (7), 1116-1119.
103. Wilhelm, S. M.; Adnane, L.; Newell, P.; Villanueva, A.; Llovet, J. M.; Lynch, M. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol. Cancer Ther. 2008, 7 (10), 3129-3140.
104. Mancuso, A.; Sternberg, C. N. New treatment approaches in metastatic renal cell carcinoma. Curr. Opin. Urol. 2006, 16 (5), 337-341.
105. ClinicalTrials.gov. A service of the U.S. National Institute of Health. http://clinicaltrials.gov.
106. AstraZeneca Global: RECENTIN did not meet primary endpoint in Horizon III study in metastatic colorectal cancer. http://www.astrazeneca.com/Media/Press-releases/Article/20100308-RECENTINdid-not-meet-primary-endpoint-in-Horizon-III
107. Morabito, A.; Piccirillo, M. C.; Costanzo, R.; Sandomenico, C.; Carillio, G.; Daniele, G.; Giordano, P.; Bryce, J.; Carotenuto, P.; La Rocca, A.; Di Maio, M.; Normanno, N.; Rocco, G.; Perrone, F. Vandetanib: An overview of its clinical development in NSCLC and other tumors. Drugs Today 2010, 46 (9), 683-698.
108. Tol, J.; Koopman, M.; Cats, A.; Rodenburg, C. J.; Creemers, G. J. M.; Schrama, J. G.; Erdkamp, F. L. G.; Vos, A. H.; Groeningen, C. J. V.; Sinnige, H. A. M.; Richel, D. J.; Voest, E. E.; Dijkstra, J. R.; Antonini, N. F.; Mol, L.; Dalesio, O.; Punt, C. J. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N. Engl. J. Med. 2009, 360 (6), 563-572.
109. Sandler, A.; Herbst, R. Combining targeted agents: blocking the epidermal growth factor and vascular endothelial growth factor pathways. Clin. Cancer Res. 2006, 12 (14 Pt 2), 4421s-4425s.
110. ClinicalTrials.gov: Study Of FOLFIRI Chemotherapy With Or Without Sunitinib In Patients With Metastatic Colorectal Cancer. http://clinicaltrials.gov/ct2/show/NCT00457691
111. Llovet, J. M.; Ricci, S.; Mazzaferro, V.; Hilgard, P.; Gane, E.; Blanc, JF.; de Oliveira, A. C.; Santoro, A.; Raoul, J. L.; Forner, A.; Schwartz, M.; Porta, C.; Zeuzem, S.; Bolondi, L.; Greten, T. F.; Galle, P. R.; Seitz, J. F.; Borbath, I.; Häussinger, D.; Giannaris, T.; Shan, M.; Moscovici, M.; Voliotis, D.; Jordi, B. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 2008, 359 (4), 378-390.
112. Connock, M.; Round, J.; Bayliss, S.; Tubeuf, S.; Greenheld, W.; Moore, D. Sorafenib for the treatment of advanced hepatocellular carcinoma. Health Technol. Assess 2010, 14, Suppl 1, 17-21.
113. Escudier, B.; Eisen, T.; Stadler, W. M.; Szczylik, C.; Oudard, S.; Staehler, M.; Negrier, S.; Chevreau, C.; Desai, A. A.; Rolland, F.; Demkow, T.; Hutson, T. E.; Gore, M.; Anderson, S.; Hofilena, G.; Shan, M.; Pena, C.; Lathia, C.; Bukowski, R. M. 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), 3312-3318.
114. Goodman and Gilman. The Pharmacological Basis of Therapeutics, 12th ed.; Mc Graw-Hill; 2011.
115. 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 (24), 2542-2550.
116. Miller, K.; Wang, M.; Gralow, J.; Dickler, M.; Cobleigh, M.; Perez, E. A.; Shenkier, T.; Cella, D.; Davidson, N. E. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N. Engl. J. Med. 2007, 357 (26), 2666-2676.
117. Gressett, S. M.; Shah, S. R. Intricacies of bevacizumab-induced toxicities and their management. Ann. Pharmacother. 2009, 43 (3), 490-501.
118. Scappaticci, F. A.; Skillings, J. R.; Holden, S. N.; Gerber, H. P.; Miller, K.; Kabbinavar, F.; Bergsland, E.; Ngai, J.; Holmgren, E.; Wang, J.; Hurwitz, H. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J. Natl. Cancer Inst. 2007, 99 (16), 1232-1239.
119. Jain, R. K.; Duda, D. G.; Willett, C. G.; Sahani, D. V.; Zhu, A. X.; Loeffler, J. S.; Batchelor, T. T.; Sorensen, A. G. Biomarkers of response and resistance to antiangiogenic therapy. Nat. Rev. Clin. Oncol. 2009, 6 (6), 327-338.
120. Bertolini, F.; Marighetti, P.; Shaked, Y. Cellular and soluble markers of tumor angiogenesis: from patient selection to the identification of the most appropriate post-resistance therapy. Biochim. Biophys. Acta 2010, 1806, 131-137.
121. Bhatt, R. S.; Seth, P.; Sukhatme, V. P. Biomarkers for monitoring antiangiogenic therapy. Clin. Cancer Res. 2007, 13 (2 Pt 2), 777s-780s.
122. Sessa, C.; Guibal, A.; Del Conte, G.; Rüegg, C. Biomarkers of angiogenesis for the development of antiangiogenic therapies in oncology: tools or decorations? Nat. Clin. Pract. Oncol. 2008, 5 (7), 378-391.
123. Murukesh, N.; Dive, C.; Jayson, G. C. Biomarkers of angiogenesis and their role in the development of VEGF inhibitors. Br. J. Cancer 2010, 102 (1), 8-18.
124. Loupakis, F.; Bocci, G.; Pasqualetti, G.; Fornaro, L.; Salvatore, L.; Cremolini, C.; Masi, G.; Danesi, R.; Del Tacca, M.; Falcone, A. Targeting vascular endothelial growth factor pathway in first-line treatment of metastatic colorectal cancer: state-of-the-art and future perspectives in clinical and molecular selection of patients. Curr. Cancer Drug Targets 2010, 10 (1), 37-45.
125. Maitland, M. L.; Bakris, G. L.; Black, H. R.; Chen, H. X.; Durand, J.-B.; Elliott, W. J.; Ivy, S. P.; Leier, C. V.; Lindenfeld, J.; Liu, G.; Remick, S. C.; Steingart, R.; Tang, W. H. W. Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. J. Natl. Cancer Inst. 2010, 102 (9), 596-604.
126. Jubb, A. M.; Harris, A. L. Biomarkers to predict the clinical efficacy of bevacizumab in cancer. Lancet Oncol. 2010, 11, 1172-1183.
127. Hurwitz, H.; Douglas, P. S.; Middleton, J. P.; Sledge, G. W.; Johnson, D. H.; Reardon, D. A.; Chen, D.; Rosen, O. Analysis of early hypertension (HTN) and clinical outcome with bevacizumab (BV). J. Clin. Oncol. 2010, 28 (15), 3039.
128. Rini, B. I.; Cohen, D. P.; Lu, D. R.; Chen, I.; Hariharan, S.; Gore, M. E.; Figlin, R. A.; Baum, M. S.; Motzer, R. J. Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J. Natl. Cancer Inst. 2011, 10, 1-11.
129. Jubb, A. M.; Hurwitz, H. I.; Bai, W.; Holmgren, E. B.; Tobin, P.; Guerrero, A.S.; Kabbinavar, F.; Holden, S. N.; Novotny, W. F.; Frantz, G. D.; Hillan, K. J.; Koeppen, H. Impact of vascular endothelial growth factor-A expression, thrombospondin-2 expression, and microvessel density on the treatment effect of bevacizumab in metastatic colorectal cancer. J. Clin. Oncol. 2006, 24 (2), 217-227.
130. Zaman, K.; Driscoll, R.; Hahn, D.; Werffeli, P.; Goodman, S. L.; Bauer, J.; Leyvraz, S.; Lejeune, F.; Stupp, R.; Rüegg, C. Monitoring multiple angiogenesis-related molecules in the blood of cancer patients shows a correlation between VEGF-A and MMP-9 levels before treatment and divergent changes after surgical vs. conservative therapy. Int. J. Cancer 2006, 118 (3), 755-764.
131. Kopetz, S.; Hoff, P. M.; Morris, J. S.; Wolff, R.A.; Eng, C.; Glover, K. Y.; Adinin, R.; Overman, M. J.; Valero, V.; Wen, S.; Lieu, C.; Yan, S.; Tran, H. T.; Ellis, L. M.; Abbruzzese, J. L.; Heymach, J. V. 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 (3), 453-459.
132. Willett, C. G.; Duda, D. G.; Tomaso, E. di; Boucher, Y.; Ancukiewicz, M.; Sahani, D. V.; Lahdenranta, J.; Chung, D. C.; Fischman, A. J.; Lauwers, G. Y.; Shellito, P.; Czito, B. G.; Wong, T. Z.; Paulson, E.; Poleski, M.; Vujaskovic, Z.; Bentley, R.; Chen, H. X.; Clark, J. W.; Jain, R. K. Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J. Clin. Oncol. 2009, 27 (18), 3020-3026.
133. Del Vecchio, M.; Mortarini, R.; Canova, S.; Di Guardo, L.; Pimpinelli, N.; Sertoli, M. R.; Bedognetti, D.; Queirolo, P.; Morosini, P.P.T.; Bajetta E.; Anichini, A. Bevacizumab plus fotemustine as first-line treatment in metastatic melanoma patients: clinical activity and modulation of angiogenesis and lymphangiogenesis factors. Clin. Cancer Res. 2010, 16 (23), 5862-5872.
134. Sabatino, M.; Kim-Schulze, S.; Panelli, MC.; Stroncek, D.; Wang, E.; Taback, B.; Kim, D. W.; Deraffele, G.; Pos, Z.; Marincola, F. M.; Kaufman, H. L. Serum vascular endothelial growth factor and fibronectin predict clinical response to high-dose interleukin-2 therapy. J. Clin. Oncol. 2009, 27 (16), 2645-2652.
135. Hlatky, L.; Hahnfeldt, P.; Folkman, J. Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn't tell us. J. Natl. Cancer Inst. 2002, 94 (12), 883-893.
136. Willett, C. G.; Boucher, Y.; Duda, D. G.; Di Tomaso, E.; Munn, L. L.; Tong, R. T.; Kozin, S. V.; Petit, L.; Jain, R. K.; Chung, D. C.; Sahani, D. V.; Kalva, S. P.; Cohen, K. S.; Scadden, D. T.; Fischman, A. J.; Clark, J. W.; Ryan, D. P.; Zhu, A. X.; Blaszkowsky, L. S.; Shellito, P. C.; Mino-Kenudson M.; Lauwers, G. Y. Surrogate markers for antiangiogenic therapy and doselimiting toxicities for bevacizumab with radiation and chemotherapy: Continued experience of a phase I trial in rectal cancer patients. J. Clin. Oncol. 2005, 23 (31), 8134-8136.
137. Ocak, I.; Baluk, P.; Barrett, T.; McDonald, D. M.; Choyke, P. The biologic basis of in vivo angiogenesis imaging. Front. Biosci. 2007, 12, 3601-3616.
138. Padhani, A. R.; Krohn, K.A.; Lewis, J. S.; Alber, M. Imaging oxygenation of human tumours. Eur. Radiol. 2007, 17 (4), 861-872.
139. Rosen, M. A.; Schnall, M. D. Dynamic contrast-enhanced magnetic resonance imaging for assessing tumor vascularity and vascular effects of targeted therapies in renal cell carcinoma. Clin. Cancer Res. 2007, 13 (2 Pt 2), 770s-776s.
140. Baba, Y.; Nosho, K.; Shima, K.; Irahara, N.; Chan, A. T.; Meyerhardt, J. A.; Chung, D. C.; Giovannucci, E. L.; Fuchs, C. S.; Ogino, S. HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers. Am. J. Pathol. 2010, 176 (5), 2292-2301.
141. Grothey, A.; Hedrick, E. E.; Mass, R. D.; Sarkar, S.; Suzuki, S.; Ramanathan, R. K.; Hurwitz, H. I.; Goldberg, R. M.; Sargent, D. J. Response-independent survival benefit in metastatic colorectal cancer: a comparative analysis of N9741 and AVF2107. J. Clin. Oncol. 2008, 26 (2), 183-189.
142. Spratlin, J. Ramucirumab (IMC-1121B): Monoclonal antibody inhibition of vascular endothelial growth factor receptor-2. Curr. Oncol. Rep. 2011, 13 (2), 97-102.
143. Mita, M.; Kelly, K. R.; Mita, A.; Ricart, A. D.; Romero, O.; Tolcher, A.; Hook, L.; Okereke, C.; Krivelevich, I.; Rossignol, D. P.; Giles, F. J.; Rowinsky, E. K.; Takimoto, C. Phase I study of E7820, an oral inhibitor of integrin {alpha}-2 expression with antiangiogenic properties, in patients with advanced malignancies. Clin. Cancer Res. 2011, 17 (1), 193-200.
144. Liu, W. M.; Henry, J. Y.; Meyer, B.; Bartlett, J. B.; Dalgleish, A.G.; Galustian, C. Inhibition of metastatic potential in colorectal carcinoma in vivo and in vitro using immunomodulatory drugs (IMiDs). Br. J. Cancer 2009, 101 (5), 803-812.
145. Hanahan, D.; Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 2011, 144 (5), 646-674.