AEE788: A dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity

Cancer Research

Volumn 64, Issue 14, 2004, Pages 4931-4941

  Traxler, Peter ^a   Allegrini, Peter R ^a   Brandt, Ralf ^b   Brueggen, Josef ^a   Cozens, Robert ^a   Fabbro, Doriano ^a   Grosios, Konstantina ^a   Lane, Heidi A ^a   McSheehy, Paul ^a   Mestan, Jürgen ^a   Meyer, Thomas ^a   Tang, Careen ^c   Wartmann, Markus ^a   Wood, Jeanette ^a   Caravatti, Giorgio ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

^b Vivo Pharm Pty Ltd   (Australia)

^c GEORGETOWN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 (4 HYDROXYPHENYL) 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; 6 [4 (4 ETHYL 1 PIPERAZINYLMETHYL)PHENYL] 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; 7H PYRROLO[2,3 D]PYRIMIDINE; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GADOTERIC ACID; PROTEIN TYROSINE KINASE INHIBITOR; PYRIMIDINE DERIVATIVE; SUPERPARAMAGNETIC IRON OXIDE; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR; VATALANIB;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; BLOOD VESSEL PERMEABILITY; CANCER STAGING; CELL PROLIFERATION; CONTRAST ENHANCEMENT; CONTROLLED STUDY; DELETION MUTANT; DRUG EFFICACY; DRUG INTERMITTENT THERAPY; DRUG POTENCY; DRUG TARGETING; DRUG TISSUE LEVEL; ENDOTHELIUM CELL; ENZYME INHIBITION; FEMALE; HUMAN; HUMAN CELL; IC 50; MOUSE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PRIORITY JOURNAL; PROGNOSIS; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN PHOSPHORYLATION; TUMOR; UMBILICAL VEIN;

ADENOCARCINOMA; ANGIOGENESIS INHIBITORS; ANIMALS; ANTINEOPLASTIC AGENTS; BALB 3T3 CELLS; CELL DIVISION; CELL LINE, TUMOR; ENZYME INHIBITORS; FEMALE; HUMANS; LUNG NEOPLASMS; MELANOMA, EXPERIMENTAL; MICE; MICE, INBRED BALB C; MICE, INBRED C57BL; MICE, NUDE; PHOSPHORYLATION; PURINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, ERBB-2; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 3142774878     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-03-3681     Document Type: Article

References (49)

1. Woodburn JR. The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther 1999;82:241-50.
2. Matter A. Tumor angiogenesis as a therapeutic target. Drug Discovery Today 2001; 6:1005-24.
3. Voldborg BR, Damstrup L, Spang-Thomsen M, Poulsen HS. Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials. Ann Onc 1997;8:1197-206.
4. Ciardiello F, Tortora G. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 2002;7:2958-70.
5. Traxler P. Tyrosine kinases as targets in cancer therapy - successes and failures. Exp Opin Ther Targets 2003;7:215-34.
6. Mendelsohn J, Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene 2000;19:6550-65.
7. Wood JM. Inhibition of vascular endothelial growth factor (VEGF) as a novel approach for cancer therapy. MEDICINA 2000;60(Suppl 2):41-7.
8. Bilodeau MT, Fraley ME, Hartman GD. Kinase insert domain-containing receptor kinase inhibitors as anti-angiogenic agents. Exp Opin Invest Drugs 2002;11:737-45.
9. Pegram M, Slamon D. Biological rationale for HER2/neu (c-erbB2) as a target for monocloncal antibody therapy. Semin Onocol 2000;5(Suppl. 9):13-9.
10. Moscatello DK, Holgado-Madruga M, Emlet DR, Montgomery RB, Wong AJ. Constitutive activation of phosphatidylinositol 3-kinase by a naturally occurring mutant epidermal growth factor receptor. J Biol Chem 1998;273:200-6.
11. Tang CK, Gong X-Q I, Moscatello DK, Wong AJ, Lippman ME. Epidermal growth factor receptor vIII enhances tumorgenicity in human breast cancer. Cancer Res 2000;60:3081-7.
12. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med (NY) 1995;1:27-31.
13. Parangi S, O'Reilly M, Christofori G, et al. Antiangiogenic therapy of transgenic mice impairs de novo tumor growth. Proc Natl Acad Sci USA 1996;93:2002-7.
14. Weinstat-Saslow D, Steeg PS. Angiogenesis and colonization in the tumor metastatic process: basic and applied advances. FASEB J 1994;8:401-7.
15. Folkman J. The role of angiogenesis in tumor growth. Semin Cancer Biol 1992;3: 65-71.
16. Breier G, Risau W. The role of vascular endothelial growth factor in blood vessel formation. Trends Cell Biol 1996;6:454-6.
17. Koelch W, Martiny-Baron G, Kieser A, Marme D. Regulation of the expression of the VEGF/VPS and its receptors: role in tumor angiogenesis. Breast Cancer Res Treat 1995;36:139-55.
18. Ferrara N. Vascular endothelial growth factor. Trends Cardiovasc Med 1993;3:244-50.
19. Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 1999;13:9-22.
20. Fong TA, Shawver LK, Sun L, et al. SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res 1999;59:99-106.
21. Mendelsohn J. Epidermal growth factor receptor inhibition by a monoclonal antibody as anticancer therapy. Clin Cancer Res 1997;3:2703-7.
22. Mendelsohn J. Targeted therapy: the epidermal growth factor receptor. Prog Anti-Cancer Chemother 1999;2:106-11.
23. Zhang H, Richter M, Green M. Therapeutic monoclonal antibodies for the ErbB family of receptor tyrosine kinases. Cancer Biol Ther 2003;2(4 Suppl 1):S122-6.
24. Furet P, Manley PW. Prospects for antiangiogenic therapies based upon VEGF inhibition. ACS Symposium Series 2001;796:282-98.
25. Mendel DB, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2003;9:327-37.
26. Laird AD, Vajkoczy P, Shawver LK, et al. SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res 2000;60: 4152-60.
27. Laird AD, Cherrington JM. Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents. Exp Opin Invest Drugs 2003;12:51-6.
28. Fabbro D, Garcia-Echeverria CG. Targeting protein kinases in cancer therapy. Curr Opin Drug Disc Devel 2002;5:701-12.
29. Glade-Bender J, Kandel JJ, Yamashiro DIJ. VEGF blocking therapy in the treatment of cancer. Exp Opin Biol Ther 2003;3:263-76.
30. Wakeling AE, Guy SP, Woodburn JR, et al. ZD1839 (Iressa): An orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res 2002;62:5749-54.
31. Wood JM, Bold G, Buchdunger E, et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res 2000;60:2178-89.
32. Solorzano CC, Baker CH, Bruns CJ, et al. Inhibition of growth and metastasis of human pancreatic cancer growing in nude mice by PTK 787/ZK222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases. Cancer Biother Radiopharm 2001;16:359-70.
33. Drevs J, Hofmann I, Hugenschmidt H, et al. 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;60:4819-24.
34. Drevs J, Mross K, Medinger M, et al. Surrogate markers for the assessment of biological activity of the VEGF-receptor inhibitor PTK787/ZK222584 (PTK/ZK) in two clinical trials. Proc Am Soc Clin Oncol 2002;20: Abstract 337.
35. Hennequin LF, Thomas AP, Johnstone C, et al. Design and structure-activity relationship of a new class of potent VEGF receptor tyrosine kinase inhibitors. J Med Chem 1999;42:5369-89.
36. Wedge SR, Ogilvie DJ, Dukes M, et al. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res 2002;62:4645-55.
37. Hurwitz HI, Eckhardt SG, Holden SN, et al. A phase I study of ZD6474, an oral VEGF receptor tyrosine kinase inhibitor, in patients with solid tumors Proc AACR-NCI-EORTC. Clin Cancer Res 2001;7:5.
38. Goldman CK, Kim J, Wong WL, King V, Brock T, Gillespie GY. Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: A model of glioblastoma multiforme pathophysiology. Mol Biol Cell 1993;4:121-33.
39. Maity A, Pore N, Lee J, Solomon D, O'Rourke DM. Epidermal growth factor receptor transcriptionally up-regulates vascular endothelial growth factor expression in human glioblastoma cells via a pathway involving phosphatidylinositol 3′-kinase and distinct from that induced by hypoxia. Cancer Res 2000;60:5879-88.
40. Izumi Y, Xu L, Di Tomaso E, Fukumura D, Jain RK. Tumor biology: herceptin acts as an anti-angiogenic cocktail. Nature 2002;416:279-80.
41. Petit AMV, Rak J, Hung MC, et al. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol 1997;151:1523-30.
42. Bruns CJ, Solorzano CC, Harbison MT, et al. Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res 2000;60: 2926-35.
43. Shaheen RM, Ahmad SA, Liu W, et al. Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors. Br J Cancer 2001;85:584-9.
44. Brandt R, O'Reilly T, Wood J, Cozens R. Combined inhibition of EGF-receptor and VEGF-receptor kinases produces profound anti-tumor efficacy against experimental cancer. Proc Am Assoc Cancer Res 2002;43:Abstract 5352.
45. Brandt R, Wong AML, Hynes NE. Mammary glands reconstituted with Neu/ErbB2 transformed HC11 cells provide a novel orthotopic tumor model for testing anticancer agents. Oncogene 2001;20:5459-65.
46. Bold G, Altmann KH, Frei J, et al. New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis. J Med Chem 2000;43:2310-2323. Erratum in: J Med Chem 2000;43:3200.
47. Bold G, Altmann KH, Frei J, et al. New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis. J Med Chem 2000;43:2310-2323. Erratum in: J Med Chem 2000;43:3200.
48. Drevs J, Muller-Driver R, Wittig C, et al. 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;62:4015-22.
49. Morgan B, Thomas AL, Drevs J, et al. Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinase, in patients with advanced colorectal cancer and liver metastasis: results from two Phase I studies. J Clin Oncol 2003;21:3955-64.