BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis

Cancer Research

Volumn 64, Issue 19, 2004, Pages 7099-7109

  Wilhelm, Scott M ^a   Carter, Christopher ^a   Tang, LiYa ^a   Wilkie, Dean ^a   McNabola, Angela ^a   Rong, Hong ^a   Chen, Charles ^a   Zhang, Xiaomei ^a   Vincent, Patrick ^a   McHugh, Mark ^a   Cao, Yichen ^a   Shujath, Jaleel ^a   Gawlak, Susan ^a   Eveleigh, Deepa ^a   Rowley, Bruce ^a   Liu, Li ^a   Adnane, Lila ^a   Lynch, Mark ^a   Auclair, Daniel ^a   Taylor, Ian ^a   Gedrich, Rich ^a   Voznesensky, Andrei ^a   Riedl, Bernd ^a   Post, Leonard E ^b   Bollag, Gideon ^b   Trail, Pamela A ^a   more..

^a BAYER CORPORATION   (United States)

^b ONYX PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

B RAF KINASE; FLT3 LIGAND; K RAS PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE; MUTANT PROTEIN; N (3 TRIFLUOROMETHYL 4 CHLOROPHENYL) N' [4 (2 METHYLCARBAMOYLPYRIDIN 4 YL)OXYPHENYL]UREA; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN TYROSINE KINASE; RAF PROTEIN; RAS PROTEIN; SORAFENIB; STEM CELL FACTOR; STEM CELL FACTOR RECEPTOR; UNCLASSIFIED DRUG; UREA DERIVATIVE; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 3;

ANGIOGENESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; AUTOPHOSPHORYLATION; BREAST CANCER; CANCER CELL CULTURE; CELL PROLIFERATION; COLON CANCER; CONTROLLED STUDY; DOSE RESPONSE; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; ENZYME REPRESSION; FEMALE; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; LUNG NON SMALL CELL CANCER; MOUSE; NEOVASCULARIZATION (PATHOLOGY); NONHUMAN; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TARGETING; SIGNAL TRANSDUCTION; TUMOR GROWTH; TUMOR XENOGRAFT; WILD TYPE;

ADMINISTRATION, ORAL; ANIMALS; BENZENESULFONATES; CELL LINE, TUMOR; DISEASE PROGRESSION; FEMALE; HUMANS; MAP KINASE KINASE KINASE 1; MAP KINASE KINASE KINASES; MAP KINASE SIGNALING SYSTEM; MICE; MICE, NUDE; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 3; MITOGEN-ACTIVATED PROTEIN KINASES; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; PROTO-ONCOGENE PROTEINS C-RAF; PYRIDINES; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 4944249117     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-04-1443     Document Type: Article

References (35)

1. Zwick E, Bange J, Ullrich A. Receptor tyrosine kinases as targets for anticancer drugs. Trends Mol Med 2002;8:17-23.
2. Herrera R, Sebolt-Leopold JS. Unraveling the complexities of the Raf/MAP kinase pathway for pharmacological intervention. Trends Mol Med 2002;8:S27-31.
3. Marshall CJ. MAP kinase kinase kinase, MAP kinase kinase and MAP kinase Curr Opin Genet Dev 1994;4:82-9.
4. Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2000;103:211-25.
5. Magne N, Fischel JL, Dubreuil A, et al. Influence of epidermal growth factor receptor (EGFR), p53 and intrinsic MAP kinase pathway status of tumour cells on the antiproliferative effect of ZD1839. Br J Cancer 2002;86:1518-23.
6. Barnes CJ, Bagheri-Yarmand R, Mandal M, et al. Suppression of epidermal growth factor receptor, mitogen-activated protein kinase, and PakI pathways and invasiveness of human cutaneous squamous cancer cells by the tyrosine kinase inhibitor ZD1839 (Iressa). Mol Cancer Ther 2003;2:345-51.
7. Lokker NA, Sullivan CM, Hollenbach SJ, Israel MA, Giese NA. Platelet-derived growth factor (PDGF) autocrine signaling regulates survival and mitogenic pathways in glioblastoma cells: evidence that the novel PDGF-C and PDGF-D ligands may play a role in the development of brain tumors. Cancer Res 2002;62:3729-35.
8. Doanes AM, Hegland DD, Sethi R, Kovesdi I, Bruder JT, Finkel T. VEGF stimulates MAPK through a pathway that is unique for receptor tyrosine kinases. Biochem Biophys Res Commun 1999;255:545-8.
9. Meadows KN, Bryant P, Pumiglia K. Vascular endothelial growth factor induction of the angiogenic phenotype requires Ras activation. J Biol Chem 2001;276:49289-98.
10. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature (Lond.) 2002;417:949-54.
11. Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res 2003;63:1454-7.
12. Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE. Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature (Lond.) 2002;418:934.
13. Hingorani SR, Jacobetz MA, Robertson GP, Herlyn M, Tuveson DA. Suppression of BRAF(V599E) in human melanoma abrogates transformation. Cancer Res 2003;63: 5198-202.
14. Wellbrock C, Ogilvie L, Medley D, et al. V599EB-RAF is an oncogens in melanocytes. Cancer Res 2004;64:2338-42.
15. Alavi A, Hood JD, Frausto R, Stupack DG, Cheresh DA. Role of Raf in vascular protection from distinct apoptotic stimuli. Science (Wash. DC) 2003;301:94-6.
16. Hood JD, Bednarski M, Frausto R, et al. Tumor regression by targeted gene delivery to the neovasculature. Science (Wash. DC) 2002;296:2404-7.
17. Wojnowski L, Zimmer AM, Beck TW, et al. Endothelial apoptosis in Braf-deficient mice. Nat Genet 1997;16:293-7.
18. Huser M, Luckett J, Chiloeches A, et al. MEK kinase activity is not necessary for Raf-1 function. EMBO J 2001;20:1940-51.
19. Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Investig 2003;111:1287-95.
20. Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003;349:427-34.
21. Weng DE, Usman N. Angiozyme: a novel angiogenesis inhibitor. Curr Oncol Rep 2001;3:141-6.
22. 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.
23. 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.
24. 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.
25. Adams J, Huang P, Patrick D. A strategy for the design of multiplex inhibitors for kinase-mediated signalling in angiogenesis. Curr Opin Chem Biol 2002;6:486-92.
26. Laird AD, Cherrington JM. Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents. Expert Opin Investig Drugs 2003;12:51-64.
27. Wilhelm S, Chien DS. BAY 43-9006: preclinical data. Curr Pharm Des 2002;8: 2255-7.
28. Lyons JF, Wilhelm S, Hibner B, Bollag G. Discovery of a novel Raf kinase inhibitor. Endocr Relat Cancer 2001;8:219-25.
29. 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;43:2310-23.
30. Crews CM, Alessandrini AA, Erikson RL. Mouse Erk-1 gene product is a serine/threonine protein kinase that has the potential to phosphorylate tyrosine. Proc Natl Acad Sci USA 1991;88:8845-9.
31. Qiu H, Miller WT. Regulation of the nonreceptor tyrosine kinase Brk by autophosphorylation and by autoinhibition. J Biol Chem 2002;277:34634-41.
32. Wilhelm S, Housley T, Kennure N. A novel diphenylurea raf kinase inhibitor (RKI) blocks the Raf/MEK/ERK pathway in tumor cells. Proc Am Assoc Cancer Res 2001;42:923.
33. Wan P, Garnett M, Roe S, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 2004;116:855-867.
34. Brummer T, Shaw PE, Reth M, Misawa Y. Inducible gene deletion reveals different roles for B-Raf and Raf-1 in B-cell antigen receptor signaling. EMBO J 2002;21: 5611-22.
35. Trivedi N, Sharma A, Zimmerman M, Smith C, Tuveson D, Robertson G. Inhibition of BRAF activity by the Raf kinase inhibitor BAY 43-9006 inhibits melanoma tumor development. Proc Am Assoc Cancer Res 2004;45:887.