Antiangiogenic cancer treatment: The great discovery and greater complexity (Review)

International Journal of Oncology

Volumn 49, Issue 5, 2016, Pages 1773-1784

  Maj, Ewa ^a   Papiernik, Diana ^a   Wietrzyk, Joanna ^a  

^a INSTITUTE OF IMMUNOLOGY AND EXPERIMENTAL THERAPY   (Poland)

Author keywords

Angiogenesis; Bevacizumab; Time window; Tyrosine kinase inhibitors; Vascular endothelial growth factor; Vessel normalization

Indexed keywords

ANGIOGENESIS INHIBITOR; AXITINIB; CABOZANTINIB; LENVATINIB; NINTEDANIB; PAZOPANIB; REGORAFENIB; SORAFENIB; SUNITINIB; VANDETANIB; VASCULOTROPIN;

ANTIANGIOGENIC THERAPY; CANCER CHEMOTHERAPY; CANCER RESISTANCE; CHRONIC MYELOID LEUKEMIA; COLORECTAL CANCER; DISEASE MARKER; DRUG APPROVAL; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG RESPONSE; DRUG TARGETING; GASTROINTESTINAL STROMAL TUMOR; HUMAN; INOPERABLE CANCER; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; LUNG FIBROSIS; MALIGNANT NEOPLASTIC DISEASE; METASTASIS; NEUROENDOCRINE TUMOR; NONHUMAN; PRIORITY JOURNAL; REVIEW; THYROID CANCER; THYROID MEDULLARY CARCINOMA; TUMOR VASCULARIZATION; ANIMAL; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; VASCULARIZATION;

ANGIOGENESIS INHIBITORS; ANIMALS; HUMANS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC;

EID: 84992656231     PISSN: 10196439     EISSN: 17912423     Source Type: Journal    
DOI: 10.3892/ijo.2016.3709     Document Type: Review

References (121)

1. Folkman J, Bach M, Rowe JW, Davidoff F, Lambert P, Hirsch C, Goldberg A, Hiatt HH, Glass J and Henshaw E: Tumor angiogenesis: Therapeutic implications. N Engl J Med 285: 1182-1186, 1971.
2. Ribatti D: History of research on tumor angiogenesis. Springer, New York, NY , 2009.
3. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS and Dvorak HF: Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219: 983-985, 1983.
4. Ferrara N: Vascular endothelial growth factor. Arterioscler Thromb Vasc Biol 29: 789-791, 2009.
5. Gupta K, Kshirsagar S, Li W, Gui L, Ramakrishnan S, Gupta P, Law PY and Hebbel RP: VEGF prevents apoptosis of human microvascular endothelial cells via opposing effects on MAPK/ERK and SAPK/JNK signaling. Exp Cell Res 247: 495-504, 1999.
6. Cross MJ and Claesson-Welsh L: FGF and VEGF function in angiogenesis: Signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci 22: 201-207, 2001.
7. Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell 144: 646-674, 2011.
8. Sennino B, Kuhnert F, Tabruyn SP, Mancuso MR, Hu-Lowe DD, Kuo CJ and McDonald DM: Cellular source and amount of vascular endothelial growth factor and platelet-derived growth factor in tumors determine response to angiogenesis inhibitors. Cancer Res 69: 4527-4536, 2009.
9. Goel S, Duda DG, Xu L, Munn LL , Boucher Y, Fukumura D and Jain RK: Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev 91: 1071-1121, 2011.
10. Carmeliet P and Jain RK: Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov 10: 417-427, 2011.
11. Vasudev NS and Reynolds AR: Anti-angiogenic therapy for cancer: Current progress, unresolved questions and future directions. Angiogenesis 17: 471-494, 2014.
12. Jain RK: Antiangiogenesis strategies revisited: From starving tumors to alleviating hypoxia. Cancer Cell 26: 605-622, 2014.
13. McIntyre A and Harris AL: Metabolic and hypoxic adaptation to anti-angiogenic therapy: A target for induced essentiality. EMBO Mol Med 7: 368-379, 2015.
14. W ang Z, Dabrosin C, Yin X, Fuster MM, Arreola A, Rathmell WK , Generali D, Nagaraju GP, El-Rayes B, Ribatti D, et al: Broad targeting of angiogenesis for cancer prevention and therapy. Semin Cancer Biol 35 (Suppl): S224-S243, 2015.
15. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, et al: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335-2342, 2004.
16. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R and Johnson DH: Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355: 2542-2550, 2006.
17. Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, 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 27: 1227-1234, 2009.
18. Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, et al; BO17704 Study Group: Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: Results from a randomised phase III trial (AVAiL). Ann Oncol 21: 1804-1809, 2010.
19. Al-Husein B, Abdalla M, Trepte M, Deremer DL and Somanath PR: Antiangiogenic therapy for cancer: An update. Pharmacotherapy 32: 1095-1111, 2012.
20. Poveda AM, Selle F, Hilpert F, Reuss A, Savarese A, Vergote I, Witteveen P, Bamias A, Scotto N, Mitchell L, et al: Bevacizumab combined with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan in platinum-resistant recurrent ovarian cancer: Analysis by chemotherapy cohort of the randomized phase III AURELIA trial. J Clin Oncol 33: 3836-3838, 2015.
21. L iu JF and Matulonis UA: Bevacizumab in newly diagnosed ovarian cancer. Lancet Oncol 16: 876-878, 2015.
22. K rill LS and Tewari KS: Integration of bevacizumab with chemotherapy doublets for advanced cervical cancer. Expert Opin Pharmacother 16: 675-683, 2015.
23. Crafton SM and Salani R: Beyond chemotherapy: An overview and review of targeted therapy in cervical cancer. Clin Ther 38: 449-458, 2016.
24. W u P, Nielsen TE and Clausen MH: FDA-approved small-molecule kinase inhibitors. Trends Pharmacol Sci 36: 422-439, 2015.
25. W u P, Nielsen TE and Clausen MH: Small-molecule kinase inhibitors: An analysis of FDA-approved drugs. Drug Discov Today 21: 5-10, 2016.
26. Ciombor KK and Berlin J: Aflibercept-A decoy VEGF receptor. Curr Oncol Rep 16: 368, 2014.
27. Aprile G, Rijavec E, Fontanella C, Rihawi K and Grossi F: Ramucirumab: Preclinical research and clinical development. Onco Targets Ther 7: 1997-2006, 2014.
28. Tiwari P: Ramucirumab: Boon or bane. J Egypt Natl Canc Inst 28: 133-140, 2016.
29. (http://www.fda.gov/) Accessed 22 Apr 2016.
30. Calero R, Morchon E, Johnsen JI and Serrano R: Sunitinib suppress neuroblastoma growth through degradation of MYCN and inhibition of angiogenesis. PLoS One 9: e95628, 2014.
31. Maj E, Filip-Psurska B, Switalska M, Kutner A, Wietrzyk J and Vitamin D: Vitamin D analogs potentiate the antitumor effect of imatinib mesylate in a human A549 lung tumor model. Int J Mol Sci 16: 27191-27207, 2015.
32. L egros L, Bourcier C, Jacquel A, Mahon FX, Cassuto JP, Auberger P and Pagès G: Imatinib mesylate (STI571) decreases the vascular endothelial growth factor plasma concentration in patients with chronic myeloid leukemia. Blood 104: 495-501, 2004.
33. K erbel RS, Viloria-Petit A, Klement G and Rak J: 'Accidental' anti-angiogenic drugs: anti-oncogene directed signal transduction inhibitors and conventional chemotherapeutic agents as examples. Eur J Cancer 36: 1248-1257, 2000.
34. K lement G, Baruchel S, Rak J, Man S, Clark K, Hicklin DJ, Bohlen P and Kerbel RS: Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest 105: R15-R24, 2000.
35. Man S, Bocci G, Francia G, Green SK, Jothy S, Hanahan D, Bohlen P, Hicklin DJ, Bergers G and Kerbel RS: Antitumor effects in mice of low-dose (metronomic) cyclophosphamide administered continuously through the drinking water. Cancer Res 62: 2731-2735, 2002.
36. W u H, Xin Y, Zhao J, Sun D, Li W, Hu Y and Wang S: Metronomic docetaxel chemotherapy inhibits angiogenesis and tumor growth in a gastric cancer model. Cancer Chemother Pharmacol 68: 879-887, 2011.
37. Guo XL , Lin GJ, Zhao H, Gao Y, Qian LP, Xu SR, Fu LN , Xu Q and Wang JJ: Inhibitory effects of docetaxel on expression of VEGF, bFGF and MMPs of LS174T cell. World J Gastroenterol 9: 1995-1998, 2003.
38. Blazejczyk A, Papiernik D, Porshneva K, Sadowska J and Wietrzyk J: Endothelium and cancer metastasis: Perspectives for antimetastatic therapy. Pharmacol Rep 67: 711-718, 2015.
39. Sagar SM, Yance D and Wong RK: Natural health products that inhibit angiogenesis: A potential source for investigational new agents to treat cancer-Part 1. Curr Oncol 13: 14-26, 2006.
40. Sagar SM, Yance D and Wong RK: Natural health products that inhibit angiogenesis: A potential source for investigational new agents to treat cancer-Part 2. Curr Oncol 13: 99-107, 2006.
41. Sulaiman RS, Basavarajappa HD and Corson TW: Natural product inhibitors of ocular angiogenesis. Exp Eye Res 129: 161-171, 2014.
42. Singh M, Singh P and Shukla Y: New strategies in cancer chemoprevention by phytochemicals. Front Biosci (Elite Ed) 4: 426-452, 2012.
43. K ang X, Jin S and Zhang Q: Antitumor and antiangiogenic activity of soy phytoestrogen on 7,12-dimethylbenz[alpha] anthracene-induced mammary tumors following ovariectomy in Sprague-Dawley rats. J Food Sci 74: H237-H242, 2009.
44. UifǍlean A, Schneider S, Ionescu C, Lalk M and Iuga CA: Soy isoflavones and breast cancer cell lines: molecular mechanisms and future perspectives. Molecules 21: E13, 2015.
45. W ietrzyk J, Opolski A, Madej J and Radzikowski C: Antitumour and antimetastatic effect of genistein alone or combined with cyclophosphamide in mice transplanted with various tumours depends on the route of tumour transplantation. In Vivo 14: 357-362, 2000.
46. W ietrzyk J, Opolski A, Madej J and Radzikowski C: The antitumor effect of postoperative treatment with genistein alone or combined with cyclophosphamide in mice bearing transplantable tumors. Acta Pol Pharm 57 (Suppl): 5-8, 2000.
47. W ietrzyk J, Boratynski J, Grynkiewicz G, Ryczynski A, Radzikowski C and Opolski A: Antiangiogenic and antitumour effects in vivo of genistein applied alone or combined with cyclophosphamide. Anticancer Res 21: 3893-3896, 2001.
48. Park SY, Jeong KJ, Lee J, Yoon DS, Choi WS, Kim YK , Han JW, K im YM, Kim BK and Lee HY: Hypoxia enhances LPA-induced HIF-1alpha and VEGF expression: Their inhibition by resveratrol. Cancer Lett 258: 63-69, 2007.
49. Y u H, Pan C, Zhao S, Wang Z, Zhang H and Wu W: Resveratrol inhibits tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 expression and invasion of human hepatocellular carcinoma cells. Biomed Pharmacother 62: 366-372, 2008.
50. Ma Y, Johnson CS and Trump DL: Mechanistic insights of Vitamin D anticancer effects. Vitam Horm 100: 395-431, 2016.
51. Jäpelt RB and Jakobsen J: Vitamin D in plants: A review of occurrence, analysis, and biosynthesis. Front Plant Sci 4: 136, 2013.
52. Haussler MR, Jurutka PW, Mizwicki M and Norman AW: Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)2vitamin D3: Genomic and non-genomic mechanisms. Best Pract Res Clin Endocrinol Metab 25: 543-559, 2011.
53. Feldman D, Krishnan AV, Swami S, Giovannucci E and Feldman BJ: The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer 14: 342-357, 2014.
54. O ikawa T, Hirotani K, Ogasawara H, Katayama T, Nakamura O , Iwaguchi T and Hiragun A: Inhibition of angiogenesis by vitamin D3 analogues. Eur J Pharmacol 178: 247-250, 1990.
55. Bao BY, Yao J and Lee YF: 1alpha, 25-dihydroxyvitamin D3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis. Carcinogenesis 27: 1883-1893, 2006.
56. Ben-Shoshan M, Amir S, Dang DT, Dang LH, Weisman Y and Mabjeesh NJ: 1alpha,25-dihydroxyvitamin D3 (Calcitriol) inhibits hypoxia-inducible factor-1/vascular endothelial growth factor pathway in human cancer cells. Mol Cancer Ther 6: 1433-1439, 2007.
57. Chung I, Han G, Seshadri M, Gillard BM, Yu WD, Foster BA, Trump DL and Johnson CS: Role of vitamin D receptor in the antiproliferative effects of calcitriol in tumor-derived endothelial cells and tumor angiogenesis in vivo. Cancer Res 69: 967-975, 2009.
58. Iseki K, Tatsuta M, Uehara H, Iishi H, Yano H, Sakai N and Ishiguro S: Inhibition of angiogenesis as a mechanism for inhibition by 1alpha-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 of colon carcinogenesis induced by azoxymethane in Wistar rats. Int J Cancer 81: 730-733, 1999.
59. N akagawa K, Sasaki Y, Kato S, Kubodera N and Okano T: 22-Oxa-1alpha,25-dihydroxyvitamin D3 inhibits metastasis and angiogenesis in lung cancer. Carcinogenesis 26: 1044-1054, 2005.
60. W ietrzyk J, Filip B, Milczarek M, Klopotowska D, Maciejewska M, Dabrowska K, Kurzepa A, Dzimira S, Madej J and Kutner A: The influence of 1,25-dihydroxyvitamin D3 and 1,24-dihydroxyvitamin D3 on αvβ3 integrin expression in cancer cell lines. Oncol Rep 20: 941-952, 2008.
61. Jones G, Strugnell SA and DeLuca HF: Current understanding of the molecular actions of vitamin D. Physiol Rev 78: 1193-1231, 1998.
62. Ma Y, Trump DL and Johnson CS: Vitamin D in combination cancer treatment. J Cancer 1: 101-107, 2010.
63. L eyssens C, Verlinden L and Verstuyf A: The future of vitamin D analogs. Front Physiol 5: 122, 2014.
64. Milczarek M, Psurski M, Kutner A and Wietrzyk J: Vitamin D analogs enhance the anticancer activity of 5-fluorouracil in an in vivo mouse colon cancer model. BMC Cancer 13: 294, 2013.
65. Milczarek M, Filip-Psurska B, Swiȩtnicki W, Kutner A and Wietrzyk J: Vitamin D analogs combined with 5-fluorouracil in human HT-29 colon cancer treatment. Oncol Rep 32: 491-504, 2014.
66. O kamoto R, Delansorne R, Wakimoto N, Doan NB, Akagi T, Shen M, Ho QH, Said JW and Koeffler HP: Inecalcitol, an analog of 1α,25(OH)2D3, induces growth arrest of androgen-dependent prostate cancer cells. Int J Cancer 130: 2464-2473, 2012.
67. Protiva P, Pendyala S, Nelson C, Augenlicht LH, Lipkin M and Holt PR: Calcium and 1,25-dihydroxyvitamin D3 modulate genes of immune and inflammatory pathways in the human colon: A human crossover trial. Am J Clin Nutr 103: 1224-1231, 2016.
68. L appe JM, Travers-Gustafson D, Davies KM, Recker RR and Heaney RP: Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial. Am J Clin Nutr 85: 1586-1591, 2007.
69. Jacot W, Firmin N, Roca L, Topart D, Gallet S, Durigova A, Mirr S, Abach L, Pouderoux S, D'Hondt V, et al: Impact of a tailored oral vitamin D supplementation regimen on serum 25-hydroxyvitamin D levels in early breast cancer patients: A randomized phase III study. Ann Oncol 27: 1235-1241, 2016.
70. Bjelakovic G, Gluud LL , Nikolova D, Whitfield K, Krstic G, Wetterslev J and Gluud C: Vitamin D supplementation for prevention of cancer in adults. Cochrane Database Syst Rev (6): CD007469, 2014.
71. Crew KD: Vitamin D: Are we ready to supplement for breast cancer prevention and treatment? ISRN oncology 2013, 2013. Article ID 483687. 10. 1155/2013/483687.
72. K im KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS and Ferrara N: Inhibition of vascular endothelial growth factorinduced angiogenesis suppresses tumour growth in vivo. Nature 362: 841-844, 1993.
73. Jain RK, Duda DG, Clark JW and Loeffler JS: Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol 3: 24-40, 2006.
74. Jayson GC, Hicklin DJ and Ellis LM: Antiangiogenic therapy-evolving view based on clinical trial results. Nat Rev Clin Oncol 9: 297-303, 2012.
75. Jain RK: Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy. Nat Med 7: 987-989, 2001.
76. Jain RK: Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy. Science 307: 58-62, 2005.
77. Y uan F, Chen Y, Dellian M, Safabakhsh N, Ferrara N and Jain RK: Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody. Proc Natl Acad Sci USA 93: 14765-14770, 1996.
78. Dickson PV, Hamner JB, Sims TL, Fraga CH, Ng CYC, Rajasekeran S, Hagedorn NL , McCarville MB, Stewart CF and Davidoff AM: Bevacizumab-induced transient remodeling of the vasculature in neuroblastoma xenografts results in improved delivery and efficacy of systemically administered chemotherapy. Clin Cancer Res 13: 3942-3950, 2007.
79. Myers AL, Williams RF, Ng CY, Hartwich JE and Davidoff AM: Bevacizumab-induced tumor vessel remodeling in rhabdomyosarcoma xenografts increases the effectiveness of adjuvant ionizing radiation. J Pediatr Surg 45: 1080-1085, 2010.
80. Inai T, Mancuso M, Hashizume H, Baffert F, Haskell A, Baluk P, Hu-Lowe DD, Shalinsky DR, Thurston G, Yancopoulos GD, et al: Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol 165: 35-52, 2004.
81. Z hou Q, Guo P and Gallo JM: Impact of angiogenesis inhibition by sunitinib on tumor distribution of temozolomide. Clin Cancer Res 14: 1540-1549, 2008.
82. Z hou Q and Gallo JM: Differential effect of sunitinib on the distribution of temozolomide in an orthotopic glioma model. Neuro oncol 11: 301-310, 2009.
83. W illett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL , Tong RT, Chung DC, Sahani DV, Kalva SP, Kozin SV, et al: Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10: 145-147, 2004.
84. Shi S, Chen L and Huang G: Antiangiogenic therapy improves the antitumor effect of adoptive cell immunotherapy by normalizing tumor vasculature. Med Oncol 30: 698, 2013.
85. Huang Y, Yuan J, Righi E, Kamoun WS, Ancukiewicz M, Nezivar J, Santosuosso M, Martin JD, Martin MR, Vianello F, et al: Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc Natl Acad Sci USA 109: 17561-17566, 2012.
86. Mancuso MR, Davis R, Norberg SM, O'Brien S, Sennino B, Nakahara T, Yao VJ, Inai T, Brooks P, Freimark B, et al: Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J Clin Invest 116: 2610-2621, 2006.
87. Griffioen AW, Mans LA, de Graaf AMA, Nowak-Sliwinska P, de Hoog CL, de Jong TAM, Vyth-Dreese FA, van Beijnum JR, Bex A and Jonasch E: Rapid angiogenesis onset after discontinuation of sunitinib treatment of renal cell carcinoma patients. Clin Cancer Res 18: 3961-3971, 2012.
88. Wolter P, Beuselinck B, Pans S and Schöffski P: Flare-up: An often unreported phenomenon nevertheless familiar to oncologists prescribing tyrosine kinase inhibitors. Acta Oncol 48: 621-624, 2009.
89. Chen DR, Lin C and Wang YF: Window of opportunity: A new insight into sequential bevacizumab and paclitaxel in two cases of metastatic triple-negative breast cancer. Exp Ther Med 10: 885-888, 2015.
90. L ee CG, Heijn M, di Tomaso E, Griffon-Etienne G, Ancukiewicz M, Koike C, Park KR, Ferrara N, Jain RK, Suit HD, et al: Anti-Vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions. Cancer Res 60: 5565-5570, 2000.
91. Z hang L, Takara K, Yamakawa D, Kidoya H and Takakura N: Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy. Cancer Sci 107: 36-44, 2016.
92. McGee MC, Hamner JB, Williams RF, Rosati SF, Sims TL, Ng CY, Gaber MW, Calabrese C, Wu J, Nathwani AC, et al: Improved intratumoral oxygenation through vascular normalization increases glioma sensitivity to ionizing radiation. Int J Radiat Oncol Biol Phys 76: 1537-1545, 2010.
93. Dings RPM, Loren M, Heun H, McNiel E, Griffioen AW, Mayo K H and Griffin RJ: Scheduling of radiation with angiogenesis inhibitors anginex and Avastin improves therapeutic outcome via vessel normalization. Clin Cancer Res 13: 3395-3402, 2007.
94. Vangestel C, Van de Wiele C, Van Damme N, Staelens S, Pauwels P, Reutelingsperger CPM and Peeters M: 99mTc-(CO)3 His-annexin A5 micro-SPECT demonstrates increased cell death by irinotecan during the vascular normalization window caused by bevacizumab. J Nucl Med 52: 1786-1794, 2011.
95. Hernandez-Agudo E, Mondejar T, Soto-Montenegro ML, Megias D, Mouron S, Sanchez J, Hidalgo M, Lopez-Casas PP, Mulero F, Desco M, et al: Monitoring vascular normalization induced by antiangiogenic treatment with F-fluoromisonidazole-PET. Mol Oncol 10: 704-718, 2015.
96. Cao Y: Off-tumor target-beneficial site for antiangiogenic cancer therapy? Nat Rev Clin Oncol 7: 604-608, 2010.
97. Y ang Y, Zhang Y, Cao Z, Ji H, Yang X, Iwamoto H, Wahlberg E, Länne T, Sun B and Cao Y: Anti-VEGF-and anti-VEGF receptor-induced vascular alteration in mouse healthy tissues. Proc Natl Acad Sci USA 110: 12018-12023, 2013.
98. W ong AK, Alfert M, Castrillon DH, Shen Q, Holash J, Yancopoulos GD and Chin L: Excessive tumor-elaborated VEGF and its neutralization define a lethal paraneoplastic syndrome. Proc Natl Acad Sci USA 98: 7481-7486, 2001.
99. Pelosof LC and Gerber DE: Paraneoplastic syndromes: An approach to diagnosis and treatment. Mayo Clin Proc 85: 838-854, 2010.
100. X ue Y, Religa P, Cao R, Hansen AJ, Lucchini F, Jones B, Wu Y , Zhu Z, Pytowski B, Liang Y, et al: Anti-VEGF agents confer survival advantages to tumor-bearing mice by improving cancer-associated systemic syndrome. Proc Natl Acad Sci USA 105: 18513-18518, 2008.
101. Cao Y: Future options of anti-angiogenic cancer therapy. Chin J Cancer 35: 21, 2016.
102. Jain RK: Normalizing tumor microenvironment to treat cancer: Bench to bedside to biomarkers. J Clin Oncol 31: 2205-2218, 2013.
103. L oges S, Schmidt T and Carmeliet P: Mechanisms of resistance to anti-angiogenic therapy and development of third-generation anti-angiogenic drug candidates. Genes Cancer 1: 12-25, 2010.
104. Bergers G and Hanahan D: Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 8: 592-603, 2008.
105. van Beijnum JR, Nowak-Sliwinska P, Huijbers EJM, Thijssen VL and Griffioen AW: The great escape; the hallmarks of resistance to antiangiogenic therapy. Pharmacol Rev 67: 441-461, 2015.
106. W illett CG, Boucher Y, Duda DG, di Tomaso E, Munn LL , Tong RT, Kozin SV, Petit L, Jain RK, Chung DC, et al: Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: Continued experience of a phase I trial in rectal cancer patients. J Clin Oncol 23: 8136-8139, 2005.
107. K opetz S, Hoff PM, Morris JS, Wolff RA, Eng C, Glover KY , Adinin R, Overman MJ, Valero V, Wen S, 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 28: 453-459, 2010.
108. Huang D, Ding Y, Zhou M, Rini BI, Petillo D, Qian CN, Kahnoski R, Futreal PA, Furge KA and Teh BT: Interleukin-8 mediates resistance to antiangiogenic agent sunitinib in renal cell carcinoma. Cancer Res 70: 1063-1071, 2010.
109. Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen PJ, Zhu M, et al: AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11: 83-95, 2007.
110. L indholm EM, Krohn M, Iadevaia S, Kristian A, Mills GB, Mælandsmo GM and Engebraaten O: Proteomic characterization of breast cancer xenografts identifies early and late bevacizumab-induced responses and predicts effective drug combinations. Clin Cancer Res 20: 404-412, 2014.
111. Ebos JML, Lee CR, Christensen JG, Mutsaers AJ and Kerbel RS: Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy. Proc Natl Acad Sci USA 104: 17069-17074, 2007.
112. Finke J, Ko J, Rini B, Rayman P, Ireland J and Cohen P: MDSC as a mechanism of tumor escape from sunitinib mediated antiangiogenic therapy. Int Immunopharmacol 11: 856-861, 2011.
113. Shojaei F, Wu X, Malik AK, Zhong C, Baldwin ME, Schanz S, Fuh G, Gerber HP and Ferrara N: Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol 25: 911-920, 2007.
114. Shojaei F, Wu X, Zhong C, Yu L, Liang XH, Yao J, Blanchard D, Bais C, Peale FV, van Bruggen N, et al: Bv8 regulates myeloidcell-dependent tumour angiogenesis. Nature 450: 825-831, 2007.
115. Tartour E, Pere H, Maillere B, Terme M, Merillon N, Taieb J, Sandoval F, Quintin-Colonna F, Lacerda K, Karadimou A, et al: Angiogenesis and immunity: A bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy. Cancer Metastasis Rev 30: 83-95, 2011.
116. Mantovani A, Biswas SK, Galdiero MR, Sica A and Locati M: Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol 229: 176-185, 2013.
117. O rimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R, Carey VJ, Richardson AL and Weinberg RA: Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121: 335-348, 2005.
118. Crawford Y, Kasman I, Yu L, Zhong C, Wu X, Modrusan Z , Kaminker J and Ferrara N: PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. Cancer Cell 15: 21-34, 2009.
119. Gerhardt H and Betsholtz C: Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 314: 15-23, 2003.
120. W elti J, Loges S, Dimmeler S and Carmeliet P: Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer. J Clin Invest 123: 3190-3200, 2013.
121. Soda Y, Myskiw C, Rommel A and Verma IM: Mechanisms of neovascularization and resistance to anti-angiogenic therapies in glioblastoma multiforme. J Mol Med (Berl) 91: 439-448, 2013.