B-Raf kinase inhibitors for cancer treatment

Current Opinion in Investigational Drugs

Volumn 8, Issue 6, 2007, Pages 452-456

  Li, Nanxin ^a   Batt, David ^b   Warmuth, Markus ^a  

^a GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION   (United States)

^b NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

B Raf; ERK; MEK; Melanoma; Raf kinase

Indexed keywords

B RAF KINASE; CARBOPLATIN; CHIR 265; PACLITAXEL; PLX 4032; SB 590885; SORAFENIB; UNCLASSIFIED DRUG; XL 281;

CANCER; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MELANOMA; NONHUMAN; REVIEW;

ANIMALS; ANTINEOPLASTIC AGENTS; BENZENESULFONATES; ENZYME INHIBITORS; HUMANS; IMIDAZOLES; NEOPLASMS; PROTO-ONCOGENE PROTEINS B-RAF; PYRIDINES;

EID: 34249888184     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (56)

1. Rapp UR, Goldsborough MD, Mark GE, Bonner TI, Groffen J, Reynolds FH Jr, Stephenson JR: Structure and biological activity of v-Raf, a unique oncogene transduced by a retrovirus. Proc Natl Acad Sci USA (1983) 80(14):4218-4222.
2. Mercer KE, Pritchard CA: Raf proteins and cancer: B-Raf is identified as a mutational target. Biochim Biophys Acta (2003) 1653(1):25-40.
3. 2+ influx through L-type voltage-gated calcium channels mediate Raf-independent activation of extracellular regulated kinase in response to glucagon-like peptide-1 in pancreatic β-cells. J Biol Chem (2002) 277(50):48146-48151.
4. Dumitru CD, Ceci JD, Tsatsanis C, Kontoyiannis D, Stamatakis K, Lin JH, Patriotis C, Jenkins NA, Copeland NG, Kollias G, Tsichlis PN: TNF-α induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway. Cell (2000) 103(7):1071-1083.
5. Garnett MJ, Marais R: Guilty as charged: B-Raf is a human oncogene. Cancer Cell (2004) 6(4):313-319. • This review describes progress made in the understanding of B-Raf as an oncogene and of its role in cancer.
6. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N et al: Mutations of the BRAF gene in human cancer. Nature (2002) 417(6892):949-954. •• This is the first paper reporting the discovery of B-Raf mutations in human cancer and demonstrated that some of the mutations are activating.
7. Libra M, Malaponte G, Navolanic PM, Gangemi P, Bevelacqua V, Proietti L, Bruni B, Stivala F, Mazzarino MC, Travali S, McCubrey JA: Analysis of BRAF mutation in primary and metastatic melanoma. Cell Cycle (2005) 4(10):1382-1384.
8. Maldonado JL, Fridlyand J, Patel H, Jain AN, Busam K, Kageshita T, Ono T, Albertson DG, Pinkel D, Bastian BC: Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst (2003) 95(24):1878-1890.
9. Shinozaki M, Fujimoto A, Morton DL, Hoon DS: Incidence of BRAF oncogene mutation and clinical relevance for primary cutaneous melanomas. Clin Cancer Res (2004) 10(5):1753-1757.
10. Uribe P, Wistuba II, Gonzalez S: BRAF mutation: A frequent event in benign, atypical, and malignant melanocytic lesions of the skin. Am J Dermatopathol (2003) 25(5):365-370.
11. Yazdi AS, Palmedo G, Flaig MJ, Puchta U, Reckwerth A, Rutten A, Mentzel T, Hugel H, Hantschke M, Schmid-Wendtner MH, Kutzner H, Sander CA: Mutations of the BRAF gene in benign and malignant melanocytic lesions. J Invest Dermatol (2003) 121(5):1160-1162.
12. 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(7):1454-1457.
13. Fransen K, Klintenas M, Osterstrom A, Dimberg J, Monstein HJ, Soderkvist P: Mutation analysis of the BRAF, ARAF and RAF-1 genes in human colorectal adenocarcinomas. Carcinogenesis (2004) 25(4):527-533.
14. Wang L, Cunningham JM, Winters JL, Guenther JC, French AJ, Boardman LA, Burgart LJ, McDonnell SK, Schaid DJ, Thibodeau SN: BRAF mutations in colon cancer are not likely attributable to defective DNA mismatch repair. Cancer Res (2003) 63(17):5209-5212.
15. Lee JW, Soung YH, Kim SY, Park WS, Nam SW, Min WS, Kim SH, Lee JY, Yoo NJ, Lee SH: Mutational analysis of the ARAF gene in human cancers. APMIS (2005) 113(1):54-57.
16. Emuss V, Garnett M, Mason C, Marais R: Mutations of C-Raf are rare in human cancer because C-Raf has a low basal kinase activity compared with B-Raf. Cancer Res (2005) 65(21):9719-9726.
17. V600E mutant protein revealed that this mutation destabilized the inactive confirmation, favoring the activated state of the kinase.
18. Garnett MJ, Rana S, Paterson H, Barford D, Marais R: Wild-type and mutant B-Raf activate C-Raf through distinct mechanisms involving heterodimerization. Mol Cell (2005) 20(6):963-969.
19. Rushworth LK, Hindley AD, O'Neill E, Kolch W: Regulation and role of Raf-1/B-Raf heterodimerization. Mol Cell Biol (2006) 26(6):2262-2272.
20. Edwards RH, Ward MR, Wu H, Medina CA, Brose MS, Volpe P, Nussen-Lee S, Haupt HM, Martin AM, Herlyn M, Lessin SR, Weber BL: Absence of BRAF mutations in UV-protected mucosal melanomas. J Med Genet (2004) 41(4):270-272.
21. Niihori T, Aoki Y, Narumi Y, Neri G, Cave H, Verloes A, Okamoto N, Hennekam RC, Gillessen-Kaesbach G, Wieczorek D, Kavamura MI et al: Germline KRAS and BRAF mutations in cardio-faciocutaneous syndrome. Nat Genet (2006) 38(3):294- 296.
22. Rodriguez-Viciana P, Tetsu O, Tidyman WE, Estep AL, Conger BA, Cruz MS, McCormick F, Rauen KA: Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. Science (2006) 311(5765):1287-1290.
23. Roberts A, Allanson J, Jadico SK, Kavamura MI, Noonan J, Opitz JM, Young T, Neri G: The cardiofaciocutaneous syndrome. J Med Genet (2006) 43(11):833-842.
24. V600EB- Raf induces proliferation and developmental defects in mice and transformation of primary fibroblasts. Cancer Res (2005) 65(24):11493-11500.
25. V600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res (2005) 65(10):4238-4245.
26. Wojnowski L, Stancato LF, Zimmer AM, Hahn H, Beck TW, Larner AC, Rapp UR, Zimmer A: CRaf-1 protein kinase is essential for mouse development. Mech Dev (1998) 76(1-2):141-149.
27. Huser M, Luckett J, Chiloeches A, Mercer K, Iwobi M, Giblett S, Sun XM, Brown J, Marais R, Pritchard C: MEK kinase activity is not necessary for Raf-1 function. EMBO J (2001) 20(8):1940-1951.
28. Mikula M, Schreiber M, Husak Z, Kucerova L, Ruth J, Wieser R, Zatloukal K, Beug H, Wagner EF, Baccarini M: Embryonic lethality and fetal liver apoptosis in mice lacking the C-Raf-1 gene. EMBO J (2001) 20(8):1952-1962.
29. Mercer K, Chiloeches A, Huser M, Kiernan M, Marais R, Pritchard C: ERK signalling and oncogene transformation are not impaired in cells lacking A-Raf. Oncogene (2002) 21(3):347-355.
30. Wojnowski L, Zimmer AM, Beck TW, Hahn H, Bernal R, Rapp UR, Zimmer A: Endothelial apoptosis in BRAF-deficient mice. Nat Genet (1997) 16(3):293-297.
31. Wiese S, Pei G, Karch C, Troppmair J, Holtmann B, Rapp UR, Sendtner M: Specific function of B-Raf in mediating survival of embryonic motoneurons and sensory neurons. Nat Neurosci (2001) 4(2):137-142.
32. V599E in human melanoma abrogates transformation. Cancer Res (2003) 63(17):5198-5202.
33. Salvatore G, De Falco V, Salerno P, Nappi TC, Pepe S, Troncone G, Carlomagno F, Melillo RM, Wilhelm SM, Santoro M: BRAF is a therapeutic target in aggressive thyroid carcinoma. Clin Cancer Res (2006) 12(5):1623-1629.
34. Karasarides M, Chiloeches A, Hayward R, Niculescu-Duvaz D, Scanlon I, Friedlos F, Ogilvie L, Hedley D, Martin J, Marshall CJ, Springer CJ, Marais R: B-RAF is a therapeutic target in melanoma. Oncogene (2004) 23(37):6292-6298.
35. V599EB-Raf is an oncogene in melanocytes. Cancer Res (2004) 64(7):2338-2342.
36. V600E for tumor growth and maintenance in an inducible short-hairpin RNA melanoma xenograft model.
37. Smith RA, Dumas J, Adnane L, Wilhelm SM: Recent advances in the research and development of Raf kinase inhibitors. Curr Top Med Chem (2006) 6(11):1071-1089. •• A thorough review describing the different chemical classes of Raf kinase inhibitors.
38. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y et al: 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 Res (2004) 64(19):7099-7109.
39. Panka DJ, Wang W, Atkins MB, Mier JW: The Raf inhibitor BAY 43-9006 (sorafenib) induces caspase-independent apoptosis in melanoma cells. Cancer Res (2006) 66(3):1611-1619.
40. Eisen T, Ahmad T, Flaherty KT, Gore M, Kaye S, Marais R, Gibbens I, Hackett S, James M, Schuchter LM, Nathanson KL et al: Sorafenib in advanced melanoma: A phase II randomised discontinuation trial analysis. Br J Cancer (2006) 95(5):581-586.
41. Bayer Pharmaceuticals Corp, Onyx Pharmaceuticals Inc: Phase III trial of Nexavar in patients with advanced melanoma does not meet primary endpoint. Press Release (2006): December 04. http://www.onyx- pharm.com
42. Chang YS, Adnane J, Trail PA, Levy J, Henderson A, Xue D, Bortolon E, Ichetovkin M, Chen C, McNabola A, Wilkie D et al: Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother Pharmacol (2007) 59(5):561-574.
43. Clark JW, Eder JP, Ryan D, Lathia C, Lenz HJ: Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43-9006, in patients with advanced, refractory solid tumors. Clin Cancer Res (2005) 11(15):5472-5480.
44. V600E.
45. mutB-Raf that effectively inhibits proliferation and survival of cancer cell lines with Ras/Raf pathway mutations. Proc Am Assoc Cancer Res (2006) 47:Abs 4855.
46. Venetsanakos E, Stuart D, Tan N, Ye H, Salangsang F, Aardalen K, Faure M, Heise C, Mendel D, Jallal B: CHIR-265, a novel inhibitor that targets B-Raf and VEGFR, shows efficacy in a broad range of preclinical models. Proc Am Assoc Cancer Res (2006) 47:Abs 4854.
47. Stuart DD, Aardalen KM, Lorenzana EG, Salangsang FD, Venetsanakos E, Tan N, Zhang W, Garrett E, Jallal B, Mendel DB: Characterization of a novel Raf kinase inhibitor that causes target dependent tumor regression in human melanoma xenografts expressing mutant B-Raf. Proc Am Assoc Cancer Res (2006) 47:Abs 4856.
48. Plexxikon Inc: Plexxikon files IND application for targeted cancer therapeutic PLX4032. Press Release (2006): October 03.
49. Exelixis Inc: Exelixis files IND application for XL281. Press Release (2006): October 13.
50. NCT00405587: Safety study of PLX4032 in patients with solid tumor. US National Institutes of Health, Bethesda, MD, USA (2006). www.clinicaltrials.gov/ct/show/NCT00405587
51. Garvey R: AACR-NCI-EORTC - 17th Symposium (Part VI) - Overnight Report, Molecular Targets and Cancer Therapeutics, Philadelphia, USA. IDdb Meeting Report (2005): November 14-18.
52. Tsai J, Zhang J, Bremer R, Artis R, Hirth P, Bollag G: Development of a novel inhibitor of oncogenic B-Raf. Proc Am Assoc Cancer Res (2006) 47:Abs 2412.
53. Buck E: Targeted Anticancer Therapies - Fifth International Symposium (Part II), Amsterdam, the Netherlands. IDdb Meeting Report (2007): March 08-10.
54. Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, Moses TY, Hostetter G, Wagner U, Kakareka J, Salem G et al: High frequency of BRAF mutations in nevi. Nat Genet (2003) 33(1):19-20.
55. Chudnovsky Y, Adams AE, Robbins PB, Lin Q, Khavari PA: Use of human tissue to assess the oncogenic activity of melanoma-associated mutations. Nat Genet (2005) 37(7):745-749.
56. Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, Beroukhim R, Milner DA, Granter SR, Du J, Lee C et al: Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature (2005) 436(7047):117-122.