Biomarkers in tumor angiogenesis and anti-angiogenic therapy

International Journal of Molecular Sciences

Volumn 12, Issue 10, 2011, Pages 7077-7099

  Pircher, Andreas ^a   Hilbe, Wolfgang ^a   Heidegger, Isabel ^a   Drevs, Joachim ^b   Tichelli, André ^c   Medinger, Michael ^c  

^a INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^b Tumor Center Unisantus   (Germany)

^c UNIVERSITY HOSPITAL BASEL   (Switzerland)

Author keywords

Angiogenesis; Biomarkers; Imaging techniques; Vascular endothelial

Indexed keywords

AMG 386; ANTINEOPLASTIC AGENT; BEVACIZUMAB; BRIVANIB; BRIVANIB ALANINATE; CARBOPLATIN; CEDIRANIB; FIBROBLAST GROWTH FACTOR 2; FLUOROURACIL; FOLINIC ACID; GADOTERIC ACID; IRINOTECAN; N ACETYLCOLCHINOL PHOSPHATE; NEUROPILIN 1; NEUROPILIN 2; OXALIPLATIN; PLATELET DERIVED GROWTH FACTOR; SORAFENIB; SUNITINIB; UNCLASSIFIED DRUG; VASCULOTROPIN; VASCULOTROPIN C; VASCULOTROPIN RECEPTOR; VATALANIB; ANGIOGENESIS INHIBITOR; MONOCLONAL ANTIBODY; PROTEIN KINASE INHIBITOR; TUMOR MARKER; VASCULOTROPIN A;

ADVANCED CANCER; ANTIANGIOGENIC THERAPY; ANTINEOPLASTIC ACTIVITY; BLOOD VESSEL PERMEABILITY; BREAST CANCER; CARCINOGENESIS; COLORECTAL CANCER; COMPUTER ASSISTED TOMOGRAPHY; DIARRHEA; DRUG EFFICACY; DRUG SAFETY; DYSPHONIA; ENDOTHELIUM CELL; ENZYME ACTIVATION; ENZYME INHIBITION; GASTROINTESTINAL STROMAL TUMOR; GASTROINTESTINAL TUMOR; GENE EXPRESSION REGULATION; GENETIC HETEROGENEITY; HUMAN; HYPERTENSION; KIDNEY CANCER; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; LIVER METASTASIS; LUNG NON SMALL CELL CANCER; LYMPHANGIOGENESIS; MICROVASCULATURE; NEUROENDOCRINE TUMOR; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OVERALL SURVIVAL; PROTEIN BINDING; PROTEIN PHOSPHORYLATION; PROTEIN TARGETING; REVIEW; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; TRANSGENIC MOUSE; TREATMENT RESPONSE; BLOOD; METABOLISM; NEOPLASMS; TUMOR EMBOLISM;

ANGIOGENESIS INHIBITORS; ANTIBODIES, MONOCLONAL; HUMANS; MAGNETIC RESONANCE IMAGING; NEOPLASMS; NEOPLASTIC CELLS, CIRCULATING; PROTEIN KINASE INHIBITORS; TUMOR MARKERS, BIOLOGICAL; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 80055036400     PISSN: None     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms12107077     Document Type: Review

References (102)

1. Folkman, J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 1971, 285, 1182-1186.
2. Folkman, J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nature Med. 1995, 1, 27-31.
3. Medinger, M.; Skoda, R.; Gratwohl, A.; Theocharides, A.; Buser, A.; Heim, D.; Dirnhofer, S.; Tichelli, A.; Tzankov, A. Angiogenesis and vascular endothelial growth factor-/receptor expression in myeloproliferative neoplasms: correlation with clinical parameters and JAK2- V617F mutational status. Br. J. Haematol. 2009, 146, 150-157.
4. Medinger, M.; Fischer, N.; Tzankov, A. Vascular endothelial growth factor-related pathways in hemato-lymphoid malignancies. J. Oncol. 2010, 2010, 729725.
5. Medinger, M.; Mross K. Clinical trials with anti-angiogenic agents in hematological malignancies. J. Angiogenes. Res. 2010, 2, 10.
6. Lyden, D.; Hattori K.; Dias, S.; Costa, C.; Blaikie, P.; Butros, L.; Chadburn, A.; Heissig, B.; Marks, W.; Witte, L. et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nature Med. 2001, 7, 1194-1201.
7. Rafii, S.; Lyden, D.; Benezra, R.; Hattori, K.; Heissig B. Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? Nat. Rev. Cancer 2002, 2, 826-835.
8. Peters, B.A.; Diaz, L.A.; Polyak, K.; Meszler, L.; Romans, K.; Guinan, E.C.; Antin, J.H.; Myerson, D.; Hamilton, S.R.; Vogelstein, B.; Kinzler, K.W.; Lengauer, C. Contribution of bone marrow-derived endothelial cells to human tumor vasculature. Nature Med. 2005, 11, 261-262.
9. Ferrara, N.; Gerber, H.P.; LeCouter, J. The biology of VEGF and its receptors. Nature Med. 2003, 9, 669-676.
10. Kim, K.J.; Li, B.; Winer, J.; Armanini, M.; Gillett, N.; Phillips, H.S.; Ferrara, N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 1993, 362, 841-844.
11. Risau, W. Mechanisms of angiogenesis. Nature 1997, 386, 671-674.
12. Medinger, M.; Drevs J. Receptor tyrosine kinases and anticancer therapy. Curr. Pharm. Des. 2005, 11, 1139-1149.
13. 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, 2335-2342.
14. Shweiki, D.; Itin, A.; Soffer, D.; Keshet, E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992, 359, 843-845.
15. Dor, Y.; Porat, R.; Keshet, E. Vascular endothelial growth factor and vascular adjustments to perturbations in oxygen homeostasis. Amer. J. Physiol. 2001, 280, 1367-1374.
16. Ryuto, M.; Ono, M.; Izumi, H.; Yoshida, S.; Weich, H.A.; Kohno, K.; Kuwano, M. Induction of vascular endothelial growth factor by tumor necrosis factor alpha in human glioma cells. Possible roles of SP-1. J. Biol. Chem. 1996, 271, 28220-28228.
17. Pertovaara, L.; Kaipainen, A.; Mustonen, T.; Orpana, A.; Ferrara, N.; Saksela, O.; Alitalo, K. Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells. J. Biol. Chem. 1994, 269, 6271-6274.
18. Kaelin, W.G., Jr. The von Hippel-Lindau tumor suppressor protein and clear cell renal carcinoma. Clin. Cancer Res. 2007, 13, 680-682.
19. Gille, H.; Kowalski, J.; Li, B.; LeCouter, J.; Moffat, B.; Zioncheck, T.F.; Pelletier, N.; Ferrara, N. Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2). A reassessment using novel receptor-specific vascular endothelial growth factor mutants. J. Biol. Chem. 2001, 276, 3222-3230.
20. Hattori, K.; Dias, S.; Heissig, B.; Hackett, N.R.; Lyden, D.; Tateno, M.; Hicklin, D.J.; Zhu, Z.; Witte, L.; Crystal, R.G.; Moore, M.A.; Rafii, S. Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J. Exp. Med. 2001, 193, 1005-1014.
21. Bellamy, W.T.; Richter, L.; Frutiger, Y.; Grogan, T.M. Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. Cancer Res. 1999, 59, 728-733.
22. Autiero, M.; Luttun, A.; Tjwa, M.; Carmeliet, P. Placental growth factor and its receptor, vascular endothelial growth factor receptor-1: novel targets for stimulation of ischemic tissue revascularization and inhibition of angiogenic and inflammatory disorders. J. Thromb. Haemost. 2003, 1, 1356-1370.
23. Ferrara, N.; Kerbel, R.S. Angiogenesis as a therapeutic target. Nature 2005, 438, 967-974.
24. Ellis, L.M. The role of neuropilins in cancer. Mol. Cancer Ther. 2006, 5, 1099-1107.
25. Soker, S.; Takashima, S.; Miao, H.Q.; Neufeld, G.; Klagsbrun, M.; Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 1998, 92, 735-745.
26. Kawakami, T.; Tokunaga, T.; Hatanaka, H.; Kijima, H.; Yamazaki, H.; Abe, Y.; Osamura, Y.; Inoue, H.; Ueyama, Y.; Nakamura, M. Neuropilin 1 and neuropilin 2 co-expression is significantly correlated with increased vascularity and poor prognosis in nonsmall cell lung carcinoma. Cancer 2002, 95, 2196-2201.
27. Rieger, J.; Wick, W.; Weller, M. Human malignant glioma cells express semaphorins and their receptors, neuropilins and plexins. Glia 2003, 42, 379-389.
28. Gray, M.J.; Van Buren, G.; Dallas, N.A.; Xia, L.; Wang, X.; Yang, A.D.; Somcio, R.J.; Lin, Y.G.; Lim, S.; Fan, F.; et al. Therapeutic targeting of neuropilin-2 on colorectal carcinoma cells implanted in the murine liver. J. Natl. Cancer. Inst. 2008, 100, 109-120.
29. Dallas, N.A.; Gray, M.J.; Xia, L.; Fan, F.; van Buren, G.; Gaur, P.; Samuel, S.; Lim, S.J.; Arumugam, T.; Ramachandran, V.; Wang, H.; Ellis, L.M. Neuropilin-2-mediated tumor growth and angiogenesis in pancreatic adenocarcinoma. Clin. Cancer Res. 2008, 14, 8052-8060.
30. Pan, Q.; Chanthery, Y.; Liang, W.C.; Stawicki, S.; Mak, J.; Rathore, N.; Tong, R.K.; Kowalski, J.; Yee, S.F.; Pacheco, G. et al. Blocking neuropilin-1 function has an additive effect with anti- VEGF to inhibit tumor growth. Cancer Cell 2007, 11, 53-67.
31. Dempke, W.C.; Zippel, R. Brivanib, a novel dual VEGF-R2/bFGF-R inhibitor. Anticancer Res. 2010, 30, 4477-4483.
32. Reiss, Y. Angiopoietins. Rec. Res. Cancer Res. 2010, 180, 3-13.
33. Mita, A.C.; Takimoto, C.H.; Mita, M.; Tolcher, A.; Sankhala, K.; Sarantopoulos, J.; Valdivieso, M.; Wood, L.; Rasmussen, E.; Sun, Y.N. et al. Phase 1 study of AMG 386, a selective angiopoietin 1/2-neutralizing peptibody, in combination with chemotherapy in adults with advanced solid tumors. Clin. Cancer Res. 2010, 16, 3044-3056.
34. Cunha, S.I.; Pietras, K. ALK1 as an emerging target for antiangiogenic therapy of cancer. Blood 2011, 117, 6999-7006.
35. Drevs, J.; Schneider, V. The use of vascular biomarkers and imaging studies in the early clinical development of anti-tumor agents targeting angiogenesis. J. Intern. Med. 2006, 260, 517-529.
36. 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, 217-227.
37. Sessa, C.; Guibal, A.; Del Conte, G.; Ruegg, C. Biomarkers of angiogenesis for the development of antiangiogenic therapies in oncology: tools or decorations? Nat. Clin. Pract. Oncol. 2008, 5, 378-391.
38. Wedam, S.B.; Low, J.A.; Yang, S.X.; Chow, C.K.; Choyke, P.; Danforth, D.; Hewitt, S.M.; Berman, A.; Steinberg, S.M.; Liewehr, D.J. et al. Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J. Clin. Oncol. 2006, 24, 769-777.
39. Abou-Alfa, G.K.; Schwartz, L.; Ricci, S.; Amadori, D.; Santoro, A.; Figer, A.; De Greve, J.; Douillard, J.Y.; Lathia, C.; Schwartz, B. et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J. Clin. Oncol. 2006, 24, 4293-4300.
40. Antonescu, C.R.; Yoshida, A.; Guo, T.; Chang, N.E.; Zhang, L.; Agaram, N.P.; Qin, L.X., Brennan, M.F.; Singer, S.; Maki, R.G. KDR activating mutations in human angiosarcomas are sensitive to specific kinase inhibitors. Cancer Res. 2009, 69, 7175-7179.
41. Pircher, A.; Ploner, F.; Popper, H.; Hilbe W. Rationale of a relaunch of gefitinib in Caucasian non-small cell lung cancer patients. Lung Cancer 2010, 69, 265-271.
42. Schneider, B.P.; Radovich, M.; Miller, K.D. The role of vascular endothelial growth factor genetic variability in cancer. Clin. Cancer. Res. 2009, 15, 5297-5302.
43. Schneider, B.P.; Wang, M.; Radovich, M.; Sledge, G.W.; Badve, S.; Thor, A.; Flockhart, D.A.; Hancock, B.; Davidson, N.; Gralow, J. et al. ECOG 2100. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J. Clin. Oncol. 2008, 26, 4672-4678.
44. Rini, B.I.; Cohen, D.P.; Lu, D.; Chen, I.; Hariharan, S.; Gore, M.E.; Figlin, R.A.; Baum, M.S.; Motzer, R.J. Hypertension (HTN) as a Biomarker of Efficacy in Patients (pts) with Metastatic Renal Cell Carcinoma (mRCC) Treated with Sunitinib; ACSO 2010 Genitourinary Cancers Symposium Abstract No. 312; American Society of Clinical Oncology: San Francisco, CA, USA, 2010.
45. Dahlberg, S.E.; Sandler, A.B.; Brahmer, J.R.; Schiller, J.H.; Johnson, D.H. Clinical course of advanced non-small-cell lung cancer patients experiencing hypertension during treatment with bevacizumab in combination with carboplatin and paclitaxel on ECOG 4599. J. Clin. Oncol. 2010, 28, 949-954.
46. 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. et al. Cardiovascular Toxicities Panel, Convened by the Angiogenesis Task Force of the National Cancer Institute Investigational Drug Steering Committee. Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. J. Natl. Cancer Inst. 2010, 102, 596-604.
47. Ebos, J.M.; Lee, C.R.; Kerbel, R.S. Tumor and host-mediated pathways of resistance and disease progression in response to antiangiogenic therapy. Clin. Cancer. Res. 2009, 15, 5020-5025.
48. Cascone, T.; Herynk, M.H.; Xu, L.; Du, Z.; Kadara, H.; Nilsson, M.B.; Oborn, C.J.; Park, Y.Y.; Erez, B.; Jacoby, J.J. et al. Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor-resistant human lung adenocarcinoma. J. Clin. Invest. 2011, 121, 1313-1328.
49. Ellis, L.M.; Hicklin, D.J. Pathways mediating resistance to vascular endothelial growth factortargeted therapy. Clin. Cancer. Res. 2008, 14, 6371-6375.
50. Shojaei, F; Wu, X.; Malik, A.K.; Zhong, C.; Baldwin, M.E.; Schanz, S.; Fuh, G.; Gerber, H.P.; Ferrara, N. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat. Biotechnol. 2007, 25, 911-920.
51. Shojaei, F.; Zhong, C.; Wu, X.; Yu, L.; Ferrara, N. Role of myeloid cells in tumor angiogenesis and growth. Trends Cell. Biol. 2008, 18, 372-378.
52. Mollay, C.; Wechselberger, C.; Mignogna, G.; Negri, L.; Melchiorri, P.; Barra, D.; Kreil, G. Bv8, a small protein from frog skin and its homologue from snake venom induce hyperalgesia in rats. Eur. J. Pharmacol. 1999, 374, 189-196.
53. Shojaei, F.; Wu, X.; Qu, X.; Kowanetz, M.; Yu, L.; Tan, M.; Meng, Y.G.; Ferrara, N. G-CSFinitiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models. Proc. Natl. Acad. Sci. USA 2009, 106, 6742-6747.
54. Shojaei, F.; Wu, X.; Zhong, C.; Yu, L.; Liang, X.H.; Yao, J.; Blanchard, D.; Bais, C.; Peale F.V.; van Bruggen, N.; et al. Bv8 regulates myeloid-cell-dependent tumour angiogenesis. Nature 2007, 450, 825-831.
55. Jubb, A.M.; Miller, K.D.; Rugo, H.S.; Harris, A.L.; Chen, D.; Reimann, J.D.; Cobleigh, M.A.; Schmidt, M.; Langmuir, V.K.; Hillan, K.J.; Chen, D.S.; Koeppen, H. Impact of exploratory biomarkers on the treatment effect of bevacizumab in metastatic breast cancer. Clin. Cancer. Res. 2011, 17, 372-381.
56. Dowlati, A.; Gray, R.; Sandler, A.B.; Schiller, J.H.; Johnson, D.H. Cell adhesion molecules, vascular endothelial growth factor, and basic fibroblast growth factor in patients with non-small cell lung cancer treated with chemotherapy with or without bevacizumab-an Eastern Cooperative Oncology Group Study. Clin. Cancer. Res. 2008, 14, 1407-1412.
57. 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. et al. Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance. J. Clin. Oncol. 2010, 28, 453-459.
58. Hanrahan, E.O.; Lin, H.Y.; Kim, E.S.; Yan, S.; Du, D.Z.; McKee, K.S.; Tran, H.T.; Lee, J.J.; Ryan, A.J.; Langmuir, P. et al. Distinct patterns of cytokine and angiogenic factor modulation and markers of benefit for vandetanib and/or chemotherapy in patients with non-small-cell lung cancer. J. Clin. Oncol. 2010, 28, 193-201.
59. Norden-Zfoni, A.; Desai, J.; Manola, J.; Beaudry, P.; Force, J.; Maki, R.; Folkman, J.; Bello, C.; Baum, C.; DePrimo, S.E.; Shalinsky, D.R.; Demetri, G.D.; Heymach, J.V. Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinibresistant gastrointestinal stromal tumor. Clin. Cancer. Res. 2007, 13, 2643-2650.
60. Nikolinakos, P.G.; Altorki, N.; Yankelevitz, D.; Tran, H.T.; Yan, S.; Rajagopalan, D.; Bordogna, W.; Ottesen, L.H.; Heymach, J.V. Plasma cytokine and angiogenic factor profiling identifies markers associated with tumor shrinkage in early-stage non-small cell lung cancer patients treated with pazopanib. Cancer Res. 2010, 70, 2171-2179.
61. Mancuso, P.; Burlini, A.; Pruneri, G.; Goldhirsch, A.; Martinelli, G.; Bertolini, F. Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. Blood 2001, 97, 3658-3661.
62. Mancuso, P.; Calleri, A.; Cassi, C.; Gobbi, A.; Capillo, M.; Pruneri, G.; Martinelli, G.; Bertolini, F. Circulating endothelial cells as a novel marker of angiogenesis. Adv. Exp. Med. Biol. 2003, 522, 83-97.
63. Goon, P.K.; Lip, G.Y.; Stonelake, P.S.; Blann, A.D. Circulating endothelial cells and circulating progenitor cells in breast cancer: relationship to endothelial damage/dysfunction/apoptosis, clinicopathologic factors, and the Nottingham Prognostic Index. Neoplasia 2009, 11, 771-779.
64. Farace, F.; Massard, C.; Borghi, E.; Bidart, J.M.; Soria, J.C. Vascular disrupting therapy-induced mobilization of circulating endothelial progenitor cells. Ann. Oncol. 2007, 18, 1421-1422.
65. Ronzoni, M.; Manzoni, M.; Mariucci, S.; Loupakis, F.; Brugnatelli, S.; Bencardino, K.; Rovati, B.; Tinelli, C.; Falcone, A.; Villa, E.; Danova, M. Circulating endothelial cells and endothelial progenitors as predictive markers of clinical response to bevacizumab-based first-line treatment in advanced colorectal cancer patients. Ann. Oncol. 2010, 21, 2382-2389.
66. Dellapasqua, S.; Bertolini, F.; Bagnardi, V.; Campagnoli, E.; Scarano, E.; Torrisi, R.; Shaked, Y.; Mancuso, P.; Goldhirsch, A.; Rocca, A.; Pietri, E.; Colleoni, M. Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer. J. Clin. Oncol. 2008, 26, 4899-4905.
67. Bertolini, F.; Shaked, Y.; Mancuso, P.; Kerbel, R.S. The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat. Rev. Cancer 2006, 6, 835-845.
68. Shaked, Y.; Henke, E.; Roodhart, J.M.; Mancuso, P.; Langenberg, M.H.; Colleoni, M.; Daenen, L.G.; Man, S.; Xu, P.; Emmenegger, U. et al. Rapid chemotherapy-induced acute endothelial progenitor cell mobilization: implications for antiangiogenic drugs as chemosensitizing agents. Cancer Cell 2008, 14, 263-273.
69. Morgan, B.; Thomas, A.L.; Drevs, J.; Hennig, J.; Buchert, M.; Jivan, A.; Horsfield, M.A.; Mross, K.; Ball, H.A.; Lee, L. et al. Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from two phase I studies. J. Clin. Oncol. 2003, 21, 3955-3964.
70. Mross, K.; Fasol, U.; Frost, A.; Benkelmann, R.; Kuhlmann, J.; Büchert, M.; Unger, C.; Blum, H.; Hennig, J.; Milenkova, T.P.; Tessier, J.; Krebs, A.D.; Ryan, A.J.; Fischer, R. DCE-MRI assessment of the effect of vandetanib on tumor vasculature in patients with advanced colorectal cancer and liver metastases: a randomized phase I study. J. Angiogenes. Res. 2009, 1, 5.
71. O'Connor, J.P.; Jackson, A.; Parker, G.J.; Jayson, G.C. DCE-MRI biomarkers in the clinical evaluation of antiangiogenic and vascular disrupting agents. Br. J. Cancer 2007, 96, 189-195.
72. Mross, K.; Stefanic, M.; Gmehling, D.; Frost, A.; Baas, F.; Unger, C.; Strecker, R.; Henning, J.; Gaschler-Markefski, B.; Stopfer, P. et al. Phase I study of the angiogenesis inhibitor BIBF 1120 in patients with advanced solid tumors. Clin. Cancer. Res. 2010, 16, 311-319.
73. Drevs, J.; Medinger, M.; Mross, K.; Fuxius, S.; Hennig, J.; Buechert, M.; Thomas, A.; Unger, C.; Chen, B.L.; Lebwohl, D.; Laurent, D. A phase IA, open-label, dose-escalating study of PTK787/ZK 222584 administered orally on a continuous dosing schedule in patients with advanced cancer. Anticancer Res. 2010, 30, 2335-2339.
74. Drevs, J.; Siegert, P.; Medinger, M.; Mross, K.; Strecker, R.; Zirrgiebel, U.; Harder, J.; Blum, H.; Robertson, J.; Jürgensmeier, J.M. et al. Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. J. Clin. Oncol. 2007, 25, 3045-3054.
75. Drevs, J.; Müller-Driver, R.; Wittig, C.; Fuxius, S.; Esser, N.; Hugenschmidt, H.; Konerding, M.A.; Allegrini, P.R.; Wood, J.; Hennig, J.; Unger, C.; Marmé, D. PTK787/ZK 222584, a specific vascular endothelial growth factor-receptor tyrosine kinase inhibitor, affects the anatomy of the tumor vascular bed and the functional vascular properties as detected by dynamic enhanced magnetic resonance imaging. Cancer Res. 2002, 62, 4015-4022.
76. Drevs, J.; Hofmannm, I.; Hugenschmidt, H.; Wittig, C.; Madjar, H.; Müller, M.; Wood, J.; Martiny-Baron, G.; Unger, C.; Marmé, D. Effects of PTK787/ZK 222584, a specific inhibitor of vascular endothelial growth factor receptor tyrosine kinases, on primary tumor, metastasis, vessel density, and blood flow in a murine renal cell carcinoma model. Cancer Res. 2000, 60, 4819-4824.
77. Tofts, P.S. Modeling tracer kinetics in dynamic Gd-DTPA MR imaging. J. Magn. Reson. Imaging 1997, 7, 91-101.
78. Medinger, M.; Esser, N.; Soltau, J.; Lehmann, K.M.; Konerding, M.A.; Wolloscheck, T.; Ryan, A.J.; Drevs, J. Antitumor effect of the vascular-disrupting agent ZD6126 in a murine renal cell carcinoma model. Int. J. Oncol. 2011, 38, 455-464.
79. Mross, K.; Drevs, J.; Müller, M.; Medinger, M.; Marmé, D.; Hennig, J.; Morgan, B.; Lebwohl, D.; Masson, E.; Ho, Y.Y.; Günther, C.; Laurent, D.; Unger, C. Phase I clinical and pharmacokinetic study of PTK/ZK, a multiple VEGF receptor inhibitor, in patients with liver metastases from solid tumours. Eur. J. Cancer. 2005, 41, 1291-1299.
80. Soltau, J.; Drevs, J. Mode of action and clinical impact of VEGF signaling inhibitors. Expert Rev. Anticancer Ther. 2009, 9, 649-662.
81. Kelly, R.J.; Rajan, A.; Force, J.; Lopez-Chavez, A.; Keen, C.; Cao, L.; Yu, Y.; Choyke, P.; Turkbey, B.; Raffeld, M. et al. Evaluation of KRAS mutations, angiogenic biomarkers, and DCE-MRI in patients with advanced non-small-cell lung cancer receiving sorafenib. Clin. Cancer. Res. 2011, 17, 1190-1199.
82. Maitland, M.L.; Kasza, K.E.; Karrison, T.; Moshier, K.; Sit, L.; Black, H.R.; Undevia, S.D.; Stadler, W.M.; Elliott, W.J.; Ratain, M.J. Ambulatory monitoring detects sorafenib-induced blood pressure elevations on the first day of treatment. Clin. Cancer Res. 2009, 15, 6250-6257.
83. 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. et al. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005, 65, 4389-4400.
84. Fiedler, W.; Mesters, R.; Heuser, M.; Ehninger, G.; Berdel, W.E.; Zirrgiebel, U.; Robertson, J.D.; Puchalski, T.A.; Collins, B.; Jürgensmeier, J.M.; Serve, H. An open-label, Phase I study of cediranib (RECENTIN) in patients with acute myeloid leukemia. Leuk. Res. 2010, 34, 196-202.
85. Langenberg, M.H.; van Herpen, C.M.; De Bono, J.; Schellens, J.H.; Unger, C.; Hoekman, K.; Blum, H.E.; Fiedler, W.; Drevs, J.; Le Maulf, F.; Fielding, A.; Robertson, J.; Voest, E.E. Effective strategies for management of hypertension after vascular endothelial growth factor signaling inhibition therapy: results from a phase II randomized, factorial, double-blind study of Cediranib in patients with advanced solid tumors. J. Clin. Oncol. 2009, 27, 6152-6159.
86. Motzer, R.J.; Hutson, T.E.; Tomczak, P.; Michaelson, M.D.; Bukowski, R.M.; Rixe, O.; Oudard, S.; Negrier, S.; Szczylik, C.; Kim, S.T. et al. Sunitinib versus interferon alfa in metastatic renalcell carcinoma. N. Engl. J. Med. 2007, 356, 115-124.
87. Raymond, E.; Dahan, L.; Raoul, J.L.; Bang, Y.J.; Borbath, I.; Lombard-Bohas, C.; Valle, J.; Metrakos, P.; Smith, D.; Vinik, A. et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N. Engl. J. Med. 2011, 364, 501-513.
88. Demetri, G.D.; van Oosterom, A.T.; Garrett, C.R.; Blackstein, M.E.; Shah, M.H.; Verweij, J.; McArthur, G.; Judson, I.R.; Heinrich, M.C.; Morgan, J.A. et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006, 368, 1329-1238.
89. Perez-Gracia, J.L.; Prior, C.; Guillén-Grima, F.; Segura, V.; Gonzalez, A.; Panizo, A.; Melero, I.; Grande-Pulido, E.; Gurpide, A.; Gil-Bazo, I.; Calvo, A. Identification of TNF-alpha and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array. Br. J. Cancer 2009, 101, 1876-1883.
90. Farace, F.; Gross-Goupil, M.; Tournay, E.; Taylor, M.; Vimond, N.; Jacques, N.; Billiot, F.; Mauguen, A.; Hill, C.; Escudier, B. Levels of circulating CD45(dim)CD34(+)VEGFR2(+) progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors. Br. J. Cancer 2011, 104, 1144-1150.
91. Paule, B.; Bastien, L.; Deslandes, E.; Cussenot, O.; Podgorniak, M.P.; Allory, Y.; Naïmi, B.; Porcher, R.; de La Taille, A.; Menashi, S.; Calvo, F.; Mourah, S. Soluble isoforms of vascular endothelial growth factor are predictors of response to sunitinib in metastatic renal cell carcinomas. PLoS One 2010, 5, e10715.
92. Zhu, A.X.; Sahani, D.V.; Duda, D.G.; di Tomaso, E.; Ancukiewicz, M.; Catalano, O.A.; Sindhwani, V.; Blaszkowsky, L.S.; Yoon, S.S.; Lahdenranta, J. et al. Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study. J. Clin. Oncol. 2009, 27, 3027-3035.
93. Presta, L.G.; Chen, H.; O'Connor, S.J.; Chisholm, V.; Meng, Y.G.; Krummen, L.; Winkler, M.; Ferrara, N. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997, 57, 4593-4599.
94. 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, 2542-2550.
95. 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, 2666-2676.
96. Jubb, A.M.; Harris, A.L. Biomarkers to predict the clinical efficacy of bevacizumab in cancer. Lancet Oncol. 2010, 11, 1172-1183.
97. Österlund, P.; Soveri, L.M.; Isoniemi, H.; Poussa, T.; Alanko, T.; Bono, P. Hypertension and overall survival in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy. Br. J. Cancer. 2011, 104, 599-604.
98. Rini, B.I.; Halabi, S.; Rosenberg, J.E.; Stadler, W.M.; Vaena, D.A.; Archer, L.; Atkins, J.N.; Picus, J.; Czaykowski, P.; Dutcher, J.; Small, E.J. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J. Clin. Oncol. 2010, 28, 2137-2143.
99. 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.
100. Drevs, J.; Zirrgiebel, U.; Schmidt-Gersbach, C.I.; Mross, K.; Medinger, M.; Lee, L.; Pinheiro, J.; Wood, J.; Thomas, A.L.; Unger, C.; Henry, A.; Steward, W.P.; Laurent, D.; Lebwohl, D.; Dugan, M.; Marmé, D. Soluble markers for the assessment of biological activity with PTK787/ZK 222584 (PTK/ZK), a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor in patients with advanced colorectal cancer from two phase I trials. Ann. Oncol. 2005, 16, 558-565.
101. Loupakis, F.; Cremolini, C.; Fioravanti, A.; Orlandi, P.; Salvatore, L.; Masi, G.; Di Desidero, T.; Canu, B.; Schirripa, M.; Frumento, P. et al. Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer. Br. J. Cancer. 2011, 104, 1262-1269.
102. Baar, J.; Silverman, P.; Lyons, J.; Fu, P.; Abdul-Karim, F.; Ziats, N.; Wasman, J.; Hartman, P.; Jesberger, J.; Dumadag, L. et al. A vasculature-targeting regimen of preoperative docetaxel with or without bevacizumab for locally advanced breast cancer: impact on angiogenic biomarkers. Clin. Cancer Res. 2009, 15, 3583-3590.