Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches

Cancer and Metastasis Reviews

Volumn 34, Issue 1, 2015, Pages 19-40

  Choi, Hyun Jin ^a   Armaiz Pena, Guillermo N ^a   Pradeep, Sunila ^a   Cho, Min Soon ^a   Coleman, Robert L ^a   Sood, Anil K ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b Sungkyunkwan University School of Medicine   (South Korea)

Author keywords

Angiogenesis; Anti vascular agent; Ovarian cancer; Resistance to anti VEGF therapy; Targeted therapy

Indexed keywords

ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; PROTEIN KINASE INHIBITOR; VASCULOTROPIN A;

ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; FEMALE; HUMAN; METABOLISM; NEOVASCULARIZATION, PATHOLOGIC; OVARIAN NEOPLASMS; SIGNAL TRANSDUCTION; TREATMENT OUTCOME; VASCULARIZATION;

ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC AGENTS; FEMALE; HUMANS; NEOVASCULARIZATION, PATHOLOGIC; OVARIAN NEOPLASMS; PROTEIN KINASE INHIBITORS; SIGNAL TRANSDUCTION; TREATMENT OUTCOME; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84925457982     PISSN: 01677659     EISSN: 15737233     Source Type: Journal    
DOI: 10.1007/s10555-014-9538-9     Document Type: Article

References (226)

1. Agarwal, R., & Kaye, S. B. (2003). Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nature Reviews Cancer, 3, 502–516.
2. Balvert-Locht, H. R., Coebergh, J. W., Hop, W. C., et al. (1991). Improved prognosis of ovarian cancer in The Netherlands during the period 1975–1985: a registry-based study. Gynecologic Oncology, 42, 3–8.
3. Ozols, R. F., Bundy, B. N., Greer, B. E., et al. (2003). Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a gynecologic oncology group study. Journal of Clinical Oncology, 21, 3194–3200.
4. du Bois, A., Neijt, J. P., & Thigpen, J. T. (1999). First line chemotherapy with carboplatin plus paclitaxel in advanced ovarian cancer—a new standard of care? Annals of Oncology, 10(Suppl 1), 35–41.
5. Biagi, J. J., & Eisenhauer, E. A. (2003). Systemic treatment policies in ovarian cancer: the next 10 years. International Journal of Gynecological Cancer, 13(Suppl 2), 231–240.
6. Neijt, J. P., Engelholm, S. A., Tuxen, M. K., et al. (2000). Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. Journal of Clinical Oncology, 18, 3084–3092.
7. Greenlee, R. T., Hill-Harmon, M. B., Murray, T., & Thun, M. (2001). Cancer statistics, 2001. CA: A Cancer Journal for Clinicians, 51, 15–36.
8. Gore, M. E., Fryatt, I., Wiltshaw, E., & Dawson, T. (1990). Treatment of relapsed carcinoma of the ovary with cisplatin or carboplatin following initial treatment with these compounds. Gynecologic Oncology, 36, 207–211.
9. Wernert, N., Locherbach, C., Wellmann, A., Behrens, P., & Hugel, A. (2001). Presence of genetic alterations in microdissected stroma of human colon and breast cancers. Anticancer Research, 21, 2259–2264.
10. Allinen, M., Beroukhim, R., Cai, L., et al. (2004). Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell, 6, 17–32.
11. Fukino, K., Shen, L., Patocs, A., Mutter, G. L., & Eng, C. (2007). Genomic instability within tumor stroma and clinicopathological characteristics of sporadic primary invasive breast carcinoma. JAMA, 297, 2103–2111.
12. Folkman, J. (1990). What is the evidence that tumors are angiogenesis dependent? Journal of the National Cancer Institute, 82, 4–6.
13. Eskander, R. N., & Randall, L. M. (2011). Bevacizumab in the treatment of ovarian cancer. Biologics, 5, 1–5.
14. Ferrara, N., & Kerbel, R. S. (2005). Angiogenesis as a therapeutic target. Nature, 438, 967–974.
15. Konerding, M. A., Fait, E., & Gaumann, A. (2001). 3D microvascular architecture of pre-cancerous lesions and invasive carcinomas of the colon. British Journal of Cancer, 84, 1354–1362.
16. Denekamp, J. (1982). Endothelial cell proliferation as a novel approach to targeting tumour therapy. British Journal of Cancer, 45, 136–139.
17. Hinnen, P., & Eskens, F. A. (2007). Vascular disrupting agents in clinical development. British Journal of Cancer, 96, 1159–1165.
18. Holwell, S. E., Cooper, P. A., Thompson, M. J., et al. (2002). Anti-tumor and anti-vascular effects of the novel tubulin-binding agent combretastatin A-1 phosphate. Anticancer Research, 22, 3933–3940.
19. Tozer, G. M., Prise, V. E., Wilson, J., et al. (1999). Combretastatin A-4 phosphate as a tumor vascular-targeting agent: early effects in tumors and normal tissues. Cancer Research, 59, 1626–1634.
20. Marysael, T., Ni, Y., Lerut, E., & de Witte, P. (2011). Influence of the vascular damaging agents DMXAA and ZD6126 on hypericin distribution and accumulation in RIF-1 tumors. Journal of Cancer Research and Clinical Oncology, 137, 1619–1627.
21. Nathan, P., Zweifel, M., Padhani, A. R., et al. (2012). Phase I trial of combretastatin A4 phosphate (CA4P) in combination with bevacizumab in patients with advanced cancer. Clinical Cancer Research, 18, 3428–3439.
22. Zweifel, M., Jayson, G. C., Reed, N. S., et al. (2011). Phase II trial of combretastatin A4 phosphate, carboplatin, and paclitaxel in patients with platinum-resistant ovarian cancer. Annals of Oncology, 22, 2036–2041.
23. Ching, L. M., Cao, Z., Kieda, C., Zwain, S., Jameson, M. B., & Baguley, B. C. (2002). Induction of endothelial cell apoptosis by the antivascular agent 5,6-Dimethylxanthenone-4-acetic acid. British Journal of Cancer, 86, 1937–1942.
24. Fredriksson, L., Li, H., Fieber, C., Li, X., & Eriksson, U. (2004). Tissue plasminogen activator is a potent activator of PDGF-CC. EMBO Journal, 23, 3793–3802.
25. Kazlauskas, A., & Cooper, J. A. (1989). Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins. Cell, 58, 1121–1133.
26. Antoniades, H. N., & Hunkapiller, M. W. (1983). Human platelet-derived growth factor (PDGF): amino-terminal amino acid sequence. Science, 220, 963–965.
27. Andrae, J., Gallini, R., & Betsholtz, C. (2008). Role of platelet-derived growth factors in physiology and medicine. Genes and Development, 22, 1276–1312.
28. Jain, R. K. (2003). Molecular regulation of vessel maturation. Nature Medicine, 9, 685–693.
29. Abramsson, A., Kurup, S., Busse, M., et al. (2007). Defective N-sulfation of heparan sulfate proteoglycans limits PDGF-BB binding and pericyte recruitment in vascular development. Genes and Development, 21, 316–331.
30. Benjamin, L. E., Hemo, I., & Keshet, E. (1998). A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development, 125, 1591–1598.
31. Oikawa, T., Onozawa, C., Sakaguchi, M., Morita, I., & Murota, S. (1994). Three isoforms of platelet-derived growth factors all have the capability to induce angiogenesis in vivo. Biological and Pharmaceutical Bulletin, 17, 1686–1688.
32. Lu, C., Thaker, P. H., Lin, Y. G., et al. (2008). Impact of vessel maturation on antiangiogenic therapy in ovarian cancer. American Journal of Obstetrics and Gynecology, 198(477), e471–e479. discussion 477 e479–410.
33. Valius, M., & Kazlauskas, A. (1993). Phospholipase C-gamma 1 and phosphatidylinositol 3 kinase are the downstream mediators of the PDGF receptor’s mitogenic signal. Cell, 73, 321–334.
34. Coughlin, S. R., Escobedo, J. A., & Williams, L. T. (1989). Role of phosphatidylinositol kinase in PDGF receptor signal transduction. Science, 243, 1191–1194.
35. Heldin, C. H., Ostman, A., & Ronnstrand, L. (1998). Signal transduction via platelet-derived growth factor receptors. Biochimica et Biophysica Acta, 1378, F79–F113.
36. Yao, R., & Cooper, G. M. (1995). Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science, 267, 2003–2006.
37. Huang, J. S., Huang, S. S., & Deuel, T. F. (1984). Transforming protein of simian sarcoma virus stimulates autocrine growth of SSV-transformed cells through PDGF cell-surface receptors. Cell, 39, 79–87.
38. Greenhalgh, D. G., Sprugel, K. H., Murray, M. J., & Ross, R. (1990). PDGF and FGF stimulate wound healing in the genetically diabetic mouse. American Journal of Pathology, 136, 1235–1246.
39. Hellberg, C., Ostman, A., & Heldin, C. H. (2010). PDGF and vessel maturation. Recent Results in Cancer Research, 180, 103–114.
40. Gaengel, K., Genove, G., Armulik, A., & Betsholtz, C. (2009). Endothelial-mural cell signaling in vascular development and angiogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology, 29, 630–638.
41. Quaegebeur, A., Segura, I., & Carmeliet, P. (2010). Pericytes: blood-brain barrier safeguards against neurodegeneration? Neuron, 68, 321–323.
42. Ribatti, D., Vacca, A., Roccaro, A. M., Crivellato, E., & Presta, M. (2003). Erythropoietin as an angiogenic factor. European Journal of Clinical Investigation, 33, 891–896.
43. Crawford, Y., Kasman, I., Yu, L., et al. (2009). PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. Cancer Cell, 15, 21–34.
44. Bergers, G., Song, S., Meyer-Morse, N., Bergsland, E., & Hanahan, D. (2003). Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. Journal of Clinical Investigation, 111, 1287–1295.
45. Erber, R., Thurnher, A., Katsen, A. D., et al. (2004). Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB Journal, 18, 338–340.
46. Jo, N., Mailhos, C., Ju, M., et al. (2006). Inhibition of platelet-derived growth factor B signaling enhances the efficacy of anti-vascular endothelial growth factor therapy in multiple models of ocular neovascularization. American Journal of Pathology, 168, 2036–2053.
47. Hasumi, Y., Klosowska-Wardega, A., Furuhashi, M., Ostman, A., Heldin, C. H., & Hellberg, C. (2007). Identification of a subset of pericytes that respond to combination therapy targeting PDGF and VEGF signaling. International Journal of Cancer, 121, 2606–2614.
48. Gerhardt, H., & Semb, H. (2008). Pericytes: gatekeepers in tumour cell metastasis? Journal of Molecular Medicine (Berl), 86, 135–144.
49. Alberts, D. S., Liu, P. Y., Wilczynski, S. P., et al. (2007). Phase II trial of imatinib mesylate in recurrent, biomarker positive, ovarian cancer (Southwest Oncology Group Protocol S0211). International Journal of Gynecological Cancer, 17, 784–788.
50. Coleman, R. L., Broaddus, R. R., Bodurka, D. C., et al. (2006). Phase II trial of imatinib mesylate in patients with recurrent platinum- and taxane-resistant epithelial ovarian and primary peritoneal cancers. Gynecologic Oncology, 101, 126–131.
51. Posadas, E. M., Kwitkowski, V., Kotz, H. L., et al. (2007). A prospective analysis of imatinib-induced c-KIT modulation in ovarian cancer: a phase II clinical study with proteomic profiling. Cancer, 110, 309–317.
52. Safra, T., Andreopoulou, E., Levinson, B., et al. (2010). Weekly paclitaxel with intermittent imatinib mesylate (Gleevec): tolerance and activity in recurrent epithelial ovarian cancer. Anticancer Research, 30, 3243–3247.
53. Matulonis, U. A., Berlin, S., Ivy, P., et al. (2009). Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. Journal of Clinical Oncology, 27, 5601–5606.
54. Raja, F. A., Griffin, C. L., Qian, W., et al. (2011). Initial toxicity assessment of ICON6: a randomised trial of cediranib plus chemotherapy in platinum-sensitive relapsed ovarian cancer. British Journal of Cancer, 105, 884–889.
55. Wilhelm, S., Carter, C., Lynch, M., et al. (2006). Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nature Reviews Drug Discovery, 5, 835–844.
56. Kane, R. C., Farrell, A. T., Saber, H., et al. (2006). Sorafenib for the treatment of advanced renal cell carcinoma. Clinical Cancer Research, 12, 7271–7278.
57. Kane, R. C., Farrell, A. T., Madabushi, R., et al. (2009). Sorafenib for the treatment of unresectable hepatocellular carcinoma. The Oncologist, 14, 95–100.
58. Matei, D., Sill, M. W., Lankes, H. A., et al. (2011). Activity of sorafenib in recurrent ovarian cancer and primary peritoneal carcinomatosis: a gynecologic oncology group trial. Journal of Clinical Oncology, 29, 69–75.
59. Welch, S. A., Hirte, H. W., Elit, L., et al. (2010). Sorafenib in combination with gemcitabine in recurrent epithelial ovarian cancer: a study of the Princess Margaret Hospital Phase II Consortium. International Journal of Gynecological Cancer, 20, 787–793.
60. Ramasubbaiah, R., Perkins, S. M., Schilder, J., et al. (2011). Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a phase I/II study of the Hoosier Oncology Group. Gynecologic Oncology, 123, 499–504.
61. Herzog, T. J., Scambia, G., Kim, B. G., et al. (2013). A randomized phase II trial of maintenance therapy with sorafenib in front-line ovarian carcinoma. Gynecologic Oncology, 130, 25–30.
62. Ledermann, J. A., Hackshaw, A., Kaye, S., et al. (2011). Randomized phase II placebo-controlled trial of maintenance therapy using the oral triple angiokinase inhibitor BIBF 1120 after chemotherapy for relapsed ovarian cancer. Journal of Clinical Oncology, 29, 3798–3804.
63. Izzedine, H., Buhaescu, I., Rixe, O., & Deray, G. (2007). Sunitinib malate. Cancer Chemotheraphy and Pharmacology, 60, 357–364.
64. Biagi, J. J., Oza, A. M., Chalchal, H. I., et al. (2011). A phase II study of sunitinib in patients with recurrent epithelial ovarian and primary peritoneal carcinoma: an NCIC Clinical Trials Group Study. Annals of Oncology, 22, 335–340.
65. Friedlander, M., Hancock, K. C., Rischin, D., et al. (2010). A phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer. Gynecologic Oncology, 119, 32–37.
66. Normanno, N., De Luca, A., Bianco, C., et al. (2006). Epidermal growth factor receptor (EGFR) signaling in cancer. Gene, 366, 2–16.
67. Yarden, Y., & Sliwkowski, M. X. (2001). Untangling the ErbB signalling network. Nature Reviews Molecular Cell Biology, 2, 127–137.
68. Cascone, T., Herynk, M. H., Xu, L., et al. (2011). Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor-resistant human lung adenocarcinoma. Journal of Clinical Investigation, 121, 1313–1328.
69. Viloria-Petit, A., Crombet, T., Jothy, S., et al. (2001). Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis. Cancer Research, 61, 5090–5101.
70. Vergote, I. B., Jimeno, A., Joly, F., et al. (2014). Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: a European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group, and Gynecologic Cancer Intergroup Study. Journal of Clinical Oncology, 32, 320–326.
71. Pakkala, S., & Ramalingam, S. S. (2009). Combined inhibition of vascular endothelial growth factor and epidermal growth factor signaling in non-small-cell lung cancer therapy. Clinical Lung Cancer, 10(Suppl 1), S17–S23.
72. Kimelman, D., & Kirschner, M. (1987). Synergistic induction of mesoderm by FGF and TGF-beta and the identification of an mRNA coding for FGF in the early Xenopus embryo. Cell, 51, 869–877.
73. De Moerlooze, L., Spencer-Dene, B., Revest, J. M., Hajihosseini, M., Rosewell, I., & Dickson, C. (2000). An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis. Development, 127, 483–492.
74. Beenken, A., & Mohammadi, M. (2009). The FGF family: biology, pathophysiology and therapy. Nature Reviews Drug Discovery, 8, 235–253.
75. Johnson, D. E., & Williams, L. T. (1993). Structural and functional diversity in the FGF receptor multigene family. Advances in Cancer Research, 60, 1–41.
76. Bae, J. H., & Schlessinger, J. (2010). Asymmetric tyrosine kinase arrangements in activation or autophosphorylation of receptor tyrosine kinases. Molecules and Cells, 29, 443–448.
77. Eswarakumar, V. P., Lax, I., & Schlessinger, J. (2005). Cellular signaling by fibroblast growth factor receptors. Cytokine and Growth Factor Reviews, 16, 139–149.
78. Cunningham, D. L., Sweet, S. M., Cooper, H. J., & Heath, J. K. (2010). Differential phosphoproteomics of fibroblast growth factor signaling: identification of Src family kinase-mediated phosphorylation events. Journal of Proteome Research, 9, 2317–2328.
79. Klint, P., & Claesson-Welsh, L. (1999). Signal transduction by fibroblast growth factor receptors. Frontiers in Bioscience, 4, D165–D177.
80. Presta, M., Dell’Era, P., Mitola, S., Moroni, E., Ronca, R., & Rusnati, M. (2005). Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine and Growth Factor Reviews, 16, 159–178.
81. Cross, M. J., & Claesson-Welsh, L. (2001). FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends in Pharmacological Sciences, 22, 201–207.
82. Presta, M., Tiberio, L., Rusnati, M., Dell’Era, P., & Ragnotti, G. (1991). Basic fibroblast growth factor requires a long-lasting activation of protein kinase C to induce cell proliferation in transformed fetal bovine aortic endothelial cells. Cell Regulation, 2, 719–726.
83. Shono, T., Kanetake, H., & Kanda, S. (2001). The role of mitogen-activated protein kinase activation within focal adhesions in chemotaxis toward FGF-2 by murine brain capillary endothelial cells. Experimental Cell Research, 264, 275–283.
84. Casanovas, O., Hicklin, D. J., Bergers, G., & Hanahan, D. (2005). Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell, 8, 299–309.
85. Compagni, A., Wilgenbus, P., Impagnatiello, M. A., Cotten, M., & Christofori, G. (2000). Fibroblast growth factors are required for efficient tumor angiogenesis. Cancer Research, 60, 7163–7169.
86. Giavazzi, R., Sennino, B., Coltrini, D., et al. (2003). Distinct role of fibroblast growth factor-2 and vascular endothelial growth factor on tumor growth and angiogenesis. American Journal of Pathology, 162, 1913–1926.
87. Nissen, L. J., Cao, R., Hedlund, E. M., et al. (2007). Angiogenic factors FGF2 and PDGF-BB synergistically promote murine tumor neovascularization and metastasis. Journal of Clinical Investigation, 117, 2766–2777.
88. Lieu, C., Heymach, J., Overman, M., Tran, H., & Kopetz, S. (2011). Beyond VEGF: inhibition of the fibroblast growth factor pathway and antiangiogenesis. Clinical Cancer Research, 17, 6130–6139.
89. Fujii, T., & Kuwano, H. (2010). Regulation of the expression balance of angiopoietin-1 and angiopoietin-2 by Shh and FGF-2. In Vitro Cellular and Developmental Biology - Animal, 46, 487–491.
90. Pepper, M. S., Ferrara, N., Orci, L., & Montesano, R. (1992). Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochemical and Biophysical Research Communications, 189, 824–831.
91. Kopetz, S., Hoff, P. M., Morris, J. S., et al. (2010). Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance. Journal of Clinical Oncology, 28, 453–459.
92. Batchelor, T. T., Sorensen, A. G., di Tomaso, E., et al. (2007). AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell, 11, 83–95.
93. Carmeliet, P., & Jain, R. K. (2011). Molecular mechanisms and clinical applications of angiogenesis. Nature, 473, 298–307.
94. Augustin, H. G., Koh, G. Y., Thurston, G., & Alitalo, K. (2009). Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nature Reviews Molecular Cell Biology, 10, 165–177.
95. Sundberg, C., Kowanetz, M., Brown, L. F., Detmar, M., & Dvorak, H. F. (2002). Stable expression of angiopoietin-1 and other markers by cultured pericytes: phenotypic similarities to a subpopulation of cells in maturing vessels during later stages of angiogenesis in vivo. Laboratory Investigation, 82, 387–401.
96. Winkler, F., Kozin, S. V., Tong, R. T., et al. (2004). Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell, 6, 553–563.
97. Maisonpierre, P. C., Suri, C., Jones, P. F., et al. (1997). Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science, 277, 55–60.
98. Scharpfenecker, M., Fiedler, U., Reiss, Y., & Augustin, H. G. (2005). The Tie-2 ligand angiopoietin-2 destabilizes quiescent endothelium through an internal autocrine loop mechanism. Journal of Cell Science, 118, 771–780.
99. Bach, F., Uddin, F. J., & Burke, D. (2007). Angiopoietins in malignancy. European Journal of Surgical Oncology, 33, 7–15.
100. Carmeliet, P., & Jain, R. K. (2011). Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nature Reviews Drug Discovery, 10, 417–427.
101. Falcon, B. L., Hashizume, H., Koumoutsakos, P., et al. (2009). Contrasting actions of selective inhibitors of angiopoietin-1 and angiopoietin-2 on the normalization of tumor blood vessels. American Journal of Pathology, 175, 2159–2170.
102. Koh, Y. J., Kim, H. Z., Hwang, S. I., et al. (2010). Double antiangiogenic protein, DAAP, targeting VEGF-A and angiopoietins in tumor angiogenesis, metastasis, and vascular leakage. Cancer Cell, 18, 171–184.
103. Herbst, R. S., Hong, D., Chap, L., et al. (2009). Safety, pharmacokinetics, and antitumor activity of AMG 386, a selective angiopoietin inhibitor, in adult patients with advanced solid tumors. Journal of Clinical Oncology, 27, 3557–3565.
104. Birchmeier, C., Birchmeier, W., Gherardi, E., & Vande Woude, G. F. (2003). Met, metastasis, motility and more. Nature Reviews Molecular Cell Biology, 4, 915–925.
105. Funakoshi, H., & Nakamura, T. (2003). Hepatocyte growth factor: from diagnosis to clinical applications. Clinica Chimica Acta, 327, 1–23.
106. Bottaro, D. P., Rubin, J. S., Faletto, D. L., et al. (1991). Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science, 251, 802–804.
107. Bolanos-Garcia, V. M. (2005). MET meet adaptors: functional and structural implications in downstream signalling mediated by the Met receptor. Molecular and Cellular Biochemistry, 276, 149–157.
108. Yu, J., Miehlke, S., Ebert, M. P., et al. (2000). Frequency of TPR-MET rearrangement in patients with gastric carcinoma and in first-degree relatives. Cancer, 88, 1801–1806.
109. Dharmawardana, P. G., Giubellino, A., & Bottaro, D. P. (2004). Hereditary papillary renal carcinoma type I. Current Molecular Medicine, 4, 855–868.
110. Bussolino, F., Di Renzo, M. F., Ziche, M., et al. (1992). Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. Journal of Cell Biology, 119, 629–641.
111. Kitajima, Y., Ide, T., Ohtsuka, T., & Miyazaki, K. (2008). Induction of hepatocyte growth factor activator gene expression under hypoxia activates the hepatocyte growth factor/c-Met system via hypoxia inducible factor-1 in pancreatic cancer. Cancer Science, 99, 1341–1347.
112. Kubota, T., Taiyoh, H., Matsumura, A., et al. (2009). NK4, an HGF antagonist, prevents hematogenous pulmonary metastasis by inhibiting adhesion of CT26 cells to endothelial cells. Clinical and Experimental Metastasis, 26, 447–456.
113. Sulpice, E., Ding, S., Muscatelli-Groux, B., et al. (2009). Cross-talk between the VEGF-A and HGF signalling pathways in endothelial cells. Biology of the Cell, 101, 525–539.
114. Puri, N., Khramtsov, A., Ahmed, S., et al. (2007). A selective small molecule inhibitor of c-Met, PHA665752, inhibits tumorigenicity and angiogenesis in mouse lung cancer xenografts. Cancer Research, 67, 3529–3534.
115. Cantelmo, A. R., Cammarota, R., Noonan, D. M., et al. (2010). Cell delivery of Met docking site peptides inhibit angiogenesis and vascular tumor growth. Oncogene, 29, 5286–5298.
116. Gherardi, E., Birchmeier, W., Birchmeier, C., & Woude, G. V. (2012). Targeting MET in cancer: rationale and progress. Nature Reviews Cancer, 12, 89–103.
117. Hara, S., Nakashiro, K., Klosek, S. K., Ishikawa, T., Shintani, S., & Hamakawa, H. (2006). Hypoxia enhances c-Met/HGF receptor expression and signaling by activating HIF-1alpha in human salivary gland cancer cells. Oral Oncology, 42, 593–598.
118. Ide, T., Kitajima, Y., Miyoshi, A., et al. (2006). Tumor-stromal cell interaction under hypoxia increases the invasiveness of pancreatic cancer cells through the hepatocyte growth factor/c-Met pathway. International Journal of Cancer, 119, 2750–2759.
119. Pennacchietti, S., Michieli, P., Galluzzo, M., Mazzone, M., Giordano, S., & Comoglio, P. M. (2003). Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell, 3, 347–361.
120. Qian, F., Engst, S., Yamaguchi, K., et al. (2009). Inhibition of tumor cell growth, invasion, and metastasis by EXEL-2880 (XL880, GSK1363089), a novel inhibitor of HGF and VEGF receptor tyrosine kinases. Cancer Research, 69, 8009–8016.
121. Nakagawa, T., Tohyama, O., Yamaguchi, A., et al. (2010). E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Science, 101, 210–215.
122. You, W. K., & McDonald, D. M. (2008). The hepatocyte growth factor/c-Met signaling pathway as a therapeutic target to inhibit angiogenesis. BMB Reports, 41, 833–839.
123. Shojaei, F., Lee, J. H., Simmons, B. H., et al. (2010). HGF/c-Met acts as an alternative angiogenic pathway in sunitinib-resistant tumors. Cancer Research, 70, 10090–10100.
124. Tomioka, D., Maehara, N., Kuba, K., et al. (2001). Inhibition of growth, invasion, and metastasis of human pancreatic carcinoma cells by NK4 in an orthotopic mouse model. Cancer Research, 61, 7518–7524.
125. Burgess, T., Coxon, A., Meyer, S., et al. (2006). Fully human monoclonal antibodies to hepatocyte growth factor with therapeutic potential against hepatocyte growth factor/c-Met-dependent human tumors. Cancer Research, 66, 1721–1729.
126. Martin, L. P., Sill, M., Shahin, M. S., et al. (2014). A phase II evaluation of AMG 102 (rilotumumab) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecologic Oncology, 132, 526–530.
127. Buckanovich, R. J., Berger, R., Sella, A., et al. (2011). Results from phase II randomized discontinuation trial. Journal of Clinical Oncology ASCO Annual Meeting. 29, abstract 5008.
128. Pasquale, E. B. (2008). Eph-ephrin bidirectional signaling in physiology and disease. Cell, 133, 38–52.
129. Walker-Daniels, J., Hess, A. R., Hendrix, M. J., & Kinch, M. S. (2003). Differential regulation of EphA2 in normal and malignant cells. American Journal of Pathology, 162, 1037–1042.
130. Pasquale, E. B. (1997). The Eph family of receptors. Current Opinion in Cell Biology, 9, 608–615.
131. Thaker, P. H., Deavers, M., Celestino, J., et al. (2004). EphA2 expression is associated with aggressive features in ovarian carcinoma. Clinical Cancer Research, 10, 5145–5150.
132. Cheng, N., Brantley, D. M., Liu, H., et al. (2002). Blockade of EphA receptor tyrosine kinase activation inhibits vascular endothelial cell growth factor-induced angiogenesis. Molecular Cancer Research, 1, 2–11.
133. Spannuth, W. A., Sood, A. K., & Coleman, R. L. (2008). Angiogenesis as a strategic target for ovarian cancer therapy. Nature Clinical Practice Oncology, 5, 194–204.
134. Lu, X. S., Sun, W., Ge, C. Y., Zhang, W. Z., & Fan, Y. Z. (2013). Contribution of the PI3K/MMPs/Ln-5gamma2 and EphA2/FAK/Paxillin signaling pathways to tumor growth and vasculogenic mimicry of gallbladder carcinomas. International Journal of Oncology, 42, 2103–2115.
135. Hess, A. R., Seftor, E. A., Gardner, L. M., et al. (2001). Molecular regulation of tumor cell vasculogenic mimicry by tyrosine phosphorylation: role of epithelial cell kinase (Eck/EphA2). Cancer Research, 61, 3250–3255.
136. Landen, C. N., Jr., Chavez-Reyes, A., Bucana, C., et al. (2005). Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Research, 65, 6910–6918.
137. Adam, M. G., Berger, C., Feldner, A., et al. (2013). Synaptojanin-2 binding protein stabilizes the Notch ligands DLL1 and DLL4 and inhibits sprouting angiogenesis. Circulation Research, 113, 1206–1218.
138. Hu, W., Lu, C., Dong, H. H., et al. (2011). Biological roles of the Delta family Notch ligand Dll4 in tumor and endothelial cells in ovarian cancer. Cancer Research, 71, 6030–6039.
139. Gale, N. W., Dominguez, M. G., Noguera, I., et al. (2004). Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to major defects in arterial and vascular development. Proceedings of the National Academy of Sciences of the United States of America, 101, 15949–15954.
140. Lobov, I. B., Renard, R. A., Papadopoulos, N., et al. (2007). Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting. Proceedings of the National Academy of Sciences of the United States of America, 104, 3219–3224.
141. Thurston, G., Noguera-Troise, I., & Yancopoulos, G. D. (2007). The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth. Nature Reviews Cancer, 7, 327–331.
142. Ridgway, J., Zhang, G., Wu, Y., et al. (2006). Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature, 444, 1083–1087.
143. Li, J. L., Sainson, R. C., Shi, W., et al. (2007). Delta-like 4 Notch ligand regulates tumor angiogenesis, improves tumor vascular function, and promotes tumor growth in vivo. Cancer Research, 67, 11244–11253.
144. Tolcher, A. W., Messersmith, W. A., Mikulski, S. M., et al. (2012). Phase I study of RO4929097, a gamma secretase inhibitor of notch signaling, in patients with refractory metastatic or locally advanced solid tumors. Journal of Clinical Oncology, 30, 2348–2353.
145. Sahebjam, S., Bedard, P. L., Castonguay, V., et al. (2013). A phase i study of the combination of ro4929097 and cediranib in patients with advanced solid tumours (PJC-004/NCI 8503). British Journal of Cancer, 109, 943–949.
146. Diaz-Padilla, I., Hirte, H., Oza, A. M., et al. (2013). A phase Ib combination study of RO4929097, a gamma-secretase inhibitor, and temsirolimus in patients with advanced solid tumors. Investigational New Drugs, 31, 1182–1191.
147. Strosberg, J. R., Yeatman, T., Weber, J., et al. (2012). A phase II study of RO4929097 in metastatic colorectal cancer. European Journal of Cancer, 48, 997–1003.
148. Summy, J. M., & Gallick, G. E. (2003). Src family kinases in tumor progression and metastasis. Cancer Metastasis Reviews, 22, 337–358.
149. Ma, W. W., & Adjei, A. A. (2009). Novel agents on the horizon for cancer therapy. CA: A Cancer Journal for Clinicians, 59, 111–137.
150. Frame, M. C. (2002). Src in cancer: deregulation and consequences for cell behaviour. Biochimica et Biophysica Acta, 1602, 114–130.
151. Trevino, J. G., Summy, J. M., Gray, M. J., et al. (2005). Expression and activity of SRC regulate interleukin-8 expression in pancreatic adenocarcinoma cells: implications for angiogenesis. Cancer Research, 65, 7214–7222.
152. Kanda, S., Miyata, Y., Kanetake, H., & Smithgall, T. E. (2007). Non-receptor protein-tyrosine kinases as molecular targets for antiangiogenic therapy (review). International Journal of Molecular Medicine, 20, 113–121.
153. Labrecque, L., Royal, I., Surprenant, D. S., Patterson, C., Gingras, D., & Béliveau, R. (2003). Regulation of vascular endothelial growth factor receptor-2 activity by caveolin-1 and plasma membrane cholesterol. Molecular Biology of the Cell, 14, 334–347.
154. Eliceiri, B. P., Puente, X. S., Hood, J. D., et al. (2002). Src-mediated coupling of focal adhesion kinase to integrin alpha(v)beta5 in vascular endothelial growth factor signaling. Journal of Cell Biology, 157, 149–160.
155. Kim, Y. M., Lee, Y. M., Kim, H. S., et al. (2002). TNF-related activation-induced cytokine (TRANCE) induces angiogenesis through the activation of Src and phospholipase C (PLC) in human endothelial cells. Journal of Biological Chemistry, 277, 6799–6805.
156. Laird, A. D., Li, G., Moss, K. G., et al. (2003). Src family kinase activity is required for signal tranducer and activator of transcription 3 and focal adhesion kinase phosphorylation and vascular endothelial growth factor signaling in vivo and for anchorage-dependent and -independent growth of human tumor cells. Molecular Cancer Therapeutics, 2, 461–469.
157. Bankhead, C. (2010). ESMO: failed trials dominate gyn cancer session. Accessed 14 Oct 2010.
158. McNeish, I. A., Ledermann, J. A., Webber, L. C., et al. (2013). A randomized placebo-controlled trial of saracatinib (AZD0530) plus weekly paclitaxel in platinum-resistant ovarian, fallopian-tube, or primary peritoneal cancer (SaPPrOC). Journal of Clinical Oncology, 31.
159. Hermann, C., Assmus, B., Urbich, C., Zeiher, A. M., & Dimmeler, S. (2000). Insulin-mediated stimulation of protein kinase Akt: a potent survival signaling cascade for endothelial cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 20, 402–409.
160. Granville, C. A., Memmott, R. M., Gills, J. J., & Dennis, P. A. (2006). Handicapping the race to develop inhibitors of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway. Clinical Cancer Research, 12, 679–689.
161. Frisch, S. M., & Ruoslahti, E. (1997). Integrins and anoikis. Current Opinion in Cell Biology, 9, 701–706.
162. Gerber, H. P., McMurtrey, A., Kowalski, J., et al. (1998). Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. Journal of Biological Chemistry, 273, 30336–30343.
163. Brunet, A., Bonni, A., Zigmond, M. J., et al. (1999). Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell, 96, 857–868.
164. Yang, D., Sun, Y., Hu, L., et al. (2013). Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer. Cancer Cell, 23, 186–199.
165. Bianco, R., Garofalo, S., Rosa, R., et al. (2008). Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs. British Journal of Cancer, 98, 923–930.
166. Jin, H., & Varner, J. (2004). Integrins: roles in cancer development and as treatment targets. British Journal of Cancer, 90, 561–565.
167. Ruegg, C., & Mariotti, A. (2003). Vascular integrins: pleiotropic adhesion and signaling molecules in vascular homeostasis and angiogenesis. Cellular and Molecular Life Sciences, 60, 1135–1157.
168. da Silva, R. G., Tavora, B., Robinson, S. D., et al. (2010). Endothelial alpha3beta1-integrin represses pathological angiogenesis and sustains endothelial-VEGF. American Journal of Pathology, 177, 1534–1548.
169. Assoian, R. K. (1997). Anchorage-dependent cell cycle progression. Journal of Cell Biology, 136, 1–4.
170. Urbich, C., Dernbach, E., Reissner, A., Vasa, M., Zeiher, A. M., & Dimmeler, S. (2002). Shear stress-induced endothelial cell migration involves integrin signaling via the fibronectin receptor subunits alpha(5) and beta(1). Arteriosclerosis, Thrombosis, and Vascular Biology, 22, 69–75.
171. Abedi, H., & Zachary, I. (1997). Vascular endothelial growth factor stimulates tyrosine phosphorylation and recruitment to new focal adhesions of focal adhesion kinase and paxillin in endothelial cells. Journal of Biological Chemistry, 272, 15442–15451.
172. Brooks, P. C., Stromblad, S., Klemke, R., Visscher, D., Sarkar, F. H., & Cheresh, D. A. (1995). Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin. Journal of Clinical Investigation, 96, 1815–1822.
173. Gutheil, J. C., Campbell, T. N., Pierce, P. R., et al. (2000). Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal antibody to the integrin alphavbeta3. Clinical Cancer Research, 6, 3056–3061.
174. Stupp, R., & Ruegg, C. (2007). Integrin inhibitors reaching the clinic. Journal of Clinical Oncology, 25, 1637–1638.
175. Shibata, K., Kikkawa, F., Nawa, A., Suganuma, N., & Hamaguchi, M. (1997). Fibronectin secretion from human peritoneal tissue induces Mr 92,000 type IV collagenase expression and invasion in ovarian cancer cell lines. Cancer Research, 57, 5416–5420.
176. Sawada, K., Mitra, A. K., Radjabi, A. R., et al. (2008). Loss of E-cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Research, 68, 2329–2339.
177. Park, C. C., Zhang, H., Pallavicini, M., et al. (2006). Beta1 integrin inhibitory antibody induces apoptosis of breast cancer cells, inhibits growth, and distinguishes malignant from normal phenotype in three dimensional cultures and in vivo. Cancer Research, 66, 1526–1535.
178. Bhaskar, V., Zhang, D., Fox, M., et al. (2007). A function blocking anti-mouse integrin alpha5beta1 antibody inhibits angiogenesis and impedes tumor growth in vivo. Journal of Translational Medicine, 5, 61.
179. Bhaskar, V., Fox, M., Breinberg, D., et al. (2008). Volociximab, a chimeric integrin alpha5beta1 antibody, inhibits the growth of VX2 tumors in rabbits. Investigational New Drugs, 26, 7–12.
180. Ramakrishnan, V., Bhaskar, V., Law, D. A., et al. (2006). Preclinical evaluation of an anti-alpha5beta1 integrin antibody as a novel anti-angiogenic agent. Journal of Experimental Therapeutics and Oncology, 5, 273–286.
181. Bell-McGuinn, K. M., Matthews, C. M., Ho, S. N., et al. (2011). A phase II, single-arm study of the anti-alpha5beta1 integrin antibody volociximab as monotherapy in patients with platinum-resistant advanced epithelial ovarian or primary peritoneal cancer. Gynecologic Oncology, 121, 273–279.
182. Naylor, M. S., Stamp, G. W., Foulkes, W. D., Eccles, D., & Balkwill, F. R. (1993). Tumor necrosis factor and its receptors in human ovarian cancer. Potential role in disease progression. Journal of Clinical Investigation, 91, 2194–2206.
183. Wu, S., Boyer, C. M., Whitaker, R. S., et al. (1993). Tumor necrosis factor alpha as an autocrine and paracrine growth factor for ovarian cancer: monokine induction of tumor cell proliferation and tumor necrosis factor alpha expression. Cancer Research, 53, 1939–1944.
184. Kulbe, H., Thompson, R., Wilson, J. L., et al. (2007). The inflammatory cytokine tumor necrosis factor-alpha generates an autocrine tumor-promoting network in epithelial ovarian cancer cells. Cancer Research, 67, 585–592.
185. Jin, D. K., Shido, K., Kopp, H. G., et al. (2006). Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes. Nature Medicine, 12, 557–567.
186. Kaplan, R. N., Riba, R. D., Zacharoulis, S., et al. (2005). VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature, 438, 820–827.
187. Kryczek, I., Lange, A., Mottram, P., et al. (2005). CXCL12 and vascular endothelial growth factor synergistically induce neoangiogenesis in human ovarian cancers. Cancer Research, 65, 465–472.
188. Aguayo, A., Kantarjian, H., Manshouri, T., et al. (2000). Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood, 96, 2240–2245.
189. Charles, K. A., Kulbe, H., Soper, R., et al. (2009). The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans. Journal of Clinical Investigation, 119, 3011–3023.
190. Kulbe, H., Chakravarty, P., Leinster, D. A., et al. (2012). A dynamic inflammatory cytokine network in the human ovarian cancer microenvironment. Cancer Research, 72, 66–75.
191. Madhusudan, S., Muthuramalingam, S. R., Braybrooke, J. P., et al. (2005). Study of etanercept, a tumor necrosis factor-alpha inhibitor, in recurrent ovarian cancer. Journal of Clinical Oncology, 23, 5950–5959.
192. Giuntoli, R. L., 2nd, Webb, T. J., Zoso, A., et al. (2009). Ovarian cancer-associated ascites demonstrates altered immune environment: implications for antitumor immunity. Anticancer Research, 29, 2875–2884.
193. Lane, D., Matte, I., Rancourt, C., & Piche, A. (2011). Prognostic significance of IL-6 and IL-8 ascites levels in ovarian cancer patients. BMC Cancer, 11, 210.
194. Dankbar, B., Padro, T., Leo, R., et al. (2000). Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma. Blood, 95, 2630–2636.
195. Nilsson, M. B., Langley, R. R., & Fidler, I. J. (2005). Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine. Cancer Research, 65, 10794–10800.
196. Rabinovich, A., Medina, L., Piura, B., Segal, S., & Huleihel, M. (2007). Regulation of ovarian carcinoma SKOV-3 cell proliferation and secretion of MMPs by autocrine IL-6. Anticancer Research, 27, 267–272.
197. Scambia, G., Testa, U., Benedetti Panici, P., et al. (1995). Prognostic significance of interleukin 6 serum levels in patients with ovarian cancer. British Journal of Cancer, 71, 354–356.
198. Guo, Y., Nemeth, J., O’Brien, C., et al. (2010). Effects of siltuximab on the IL-6-induced signaling pathway in ovarian cancer. Clinical Cancer Research, 16, 5759–5769.
199. Coward, J., Kulbe, H., Chakravarty, P., et al. (2011). Interleukin-6 as a therapeutic target in human ovarian cancer. Clinical Cancer Research, 17, 6083–6096.
200. Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., & Mello, C. C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 391, 806–811.
201. Hammond, S. M., Bernstein, E., Beach, D., & Hannon, G. J. (2000). An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature, 404, 293–296.
202. Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., & Tuschl, T. (2001). Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 411, 494–498.
203. Fattal, E., & Bochot, A. (2006). Ocular delivery of nucleic acids: antisense oligonucleotides, aptamers and siRNA. Advanced Drug Delivery Reviews, 58, 1203–1223.
204. Bitko, V., Musiyenko, A., Shulyayeva, O., & Barik, S. (2005). Inhibition of respiratory viruses by nasally administered siRNA. Nature Medicine, 11, 50–55.
205. Ozpolat, B., Sood, A. K., & Lopez-Berestein, G. (2010). Nanomedicine based approaches for the delivery of siRNA in cancer. Journal of Internal Medicine, 267, 44–53.
206. Zhou, J., Shum, K. T., Burnett, J. C., & Rossi, J. J. (2013). Nanoparticle-based delivery of RNAi therapeutics: progress and challenges. Pharmaceuticals (Basel), 6, 85–107.
207. Tan, W. B., Jiang, S., & Zhang, Y. (2007). Quantum-dot based nanoparticles for targeted silencing of HER2/neu gene via RNA interference. Biomaterials, 28, 1565–1571.
208. Lee, J. H., Lee, K., Moon, S. H., Lee, Y., Park, T. G., & Cheon, J. (2009). All-in-one target-cell-specific magnetic nanoparticles for simultaneous molecular imaging and siRNA delivery. Angewandte Chemie International Edition in English, 48, 4174–4179.
209. Yu, D., Peng, P., Dharap, S. S., et al. (2005). Antitumor activity of poly(ethylene glycol)-camptothecin conjugate: the inhibition of tumor growth in vivo. Journal of Controlled Release, 110, 90–102.
210. Maeda, H. (2001). The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Advances in Enzyme Regulation, 41, 189–207.
211. Nikitenko, N. A., & Prassolov, V. S. (2013). Non-viral delivery and therapeutic application of small interfering RNAs. Acta Naturae, 5, 35–53.
212. Davis, M. E., Zuckerman, J. E., Choi, C. H., et al. (2010). Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature, 464, 1067–1070.
213. Heidel, J. D., Yu, Z., Liu, J. Y., et al. (2007). Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA. Proceedings of the National Academy of Sciences of the United States of America, 104, 5715–5721.
214. Matei, D., Emerson, R. E., Schilder, J., et al. (2008). Imatinib mesylate in combination with docetaxel for the treatment of patients with advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis: a Hoosier Oncology Group trial. Cancer, 113, 723–732.
215. Juretzka, M., Hensley, M. L., Tew, W., et al. (2008). A phase 2 trial of oral imatinib in patients with epithelial ovarian, fallopian tube, or peritoneal carcinoma in second or greater remission. European Journal of Gynaecological Oncology, 29, 568–572.
216. Liu, J. F., Tolaney, S. M., Birrer, M., et al. (2013). A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. European Journal of Cancer, 49, 2972–2978.
217. Hjalmarson, A. (1990). Heart rate and beta-adrenergic mechanisms in acute myocardial infarction. Basic Research in Cardiology, 85(Suppl 1), 325–333.
218. Bodnar, L., Gornas, M., & Szczylik, C. (2011). Sorafenib as a third line therapy in patients with epithelial ovarian cancer or primary peritoneal cancer: a phase II study. Gynecologic Oncology, 123, 33–36.
219. Campos, S. M., Penson, R. T., Matulonis, U., et al. (2013). A phase II trial of sunitinib malate in recurrent and refractory ovarian, fallopian tube and peritoneal carcinoma. Gynecologic Oncology, 128, 215–220.
220. Baumann, K. H., du Bois, A., Meier, W., et al. (2012). A phase II trial (AGO 2.11) in platinum-resistant ovarian cancer: a randomized multicenter trial with sunitinib (SU11248) to evaluate dosage, schedule, tolerability, toxicity and effectiveness of a multitargeted receptor tyrosine kinase inhibitor monotherapy. Annals of Oncology, 23, 2265–2271.
221. Karlan, B. Y., Oza, A. M., Richardson, G. E., et al. (2012). Randomized, double-blind, placebo-controlled phase II study of AMG 386 combined with weekly paclitaxel in patients with recurrent ovarian cancer. Journal of Clinical Oncology, 30, 362–371.
222. Secord, A. A., Teoh, D. K., Barry, W. T., et al. (2012). A phase I trial of dasatinib, an SRC-family kinase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer. Clinical Cancer Research, 18, 5489–5498.
223. Schilder, R. J., Brady, W. E., Lankes, H. A., et al. (2012). Phase II evaluation of dasatinib in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecologic Oncology, 127, 70–74.
224. Behbakht, K., Sill, M. W., Darcy, K. M., et al. (2011). Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: a Gynecologic Oncology Group study. Gynecologic Oncology, 123, 19–26.
225. Temkin, S. M., Yamada, S. D., & Fleming, G. F. (2010). A phase I study of weekly temsirolimus and topotecan in the treatment of advanced and/or recurrent gynecologic malignancies. Gynecologic Oncology, 117, 473–476.
226. Kollmannsberger, C., Hirte, H., Siu, L. L., et al. (2012). Temsirolimus in combination with carboplatin and paclitaxel in patients with advanced solid tumors: a NCIC-CTG, phase I, open-label dose-escalation study (IND 179). Annals of Oncology, 23, 238–244.