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Expert Opinion on Emerging Drugs Volume 14, 2009 - Issue 4
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Reviews

Emerging Raf inhibitors

James A McCubrey Brody School of Medicine at East Carolina University, Department of Microbiology & Immunology, 600 Moye Boulevard, Greenville, NC 27858, USA +1 252 744 2704; +1 252 744 3104; [email protected]
,
Linda S Steelman Brody School of Medicine at East Carolina University, Department of Microbiology & Immunology, 600 Moye Boulevard, Greenville, NC 27858, USA +1 252 744 2704; +1 252 744 3104; [email protected]
,
Steven L Abrams Brody School of Medicine at East Carolina University, Department of Microbiology & Immunology, 600 Moye Boulevard, Greenville, NC 27858, USA +1 252 744 2704; +1 252 744 3104; [email protected]
,
William H Chappell Brody School of Medicine at East Carolina University, Department of Microbiology & Immunology, 600 Moye Boulevard, Greenville, NC 27858, USA +1 252 744 2704; +1 252 744 3104; [email protected]
,
Suzanne Russo Brody School of Medicine at East Carolina University, Leo Jenkins Cancer Center, Department of Radiation Oncology, 600 Moye Blvd, Greenville 27834, USA
,
Roger Ove Brody School of Medicine at East Carolina University, Leo Jenkins Cancer Center, Department of Radiation Oncology, 600 Moye Blvd, Greenville 27834, USA
,
Michele Milella Regina Elena Cancer Center, Via Elio Chianesi n.53, Rome 00144, Italy
,
Agostino Tafuri University of Rome, Department of Hematology-Oncology, La Sapienza, Via Benevento 6, Rome 99161, Italy
,
Paolo Lunghi University of Parma, Department of Clinical Sciences, Via Gramsci n.14, Parma 43100, Italy
,
Antonio Bonati University of Parma, Department of Clinical Sciences, Via Gramsci n.14, Parma 43100, Italy; University Hospital of Parma, Unit of Hematology and Bone-Marrow Transplantation, Via Gramsi n.14, Parma 43100, Italy
,
Franca Stivala University of Catania, Department of Biological Sciences, Via Androne 83, Catania 95124, Italy
,
Ferdinando Nicoletti University of Catania, Department of Biological Sciences, Via Androne 83, Catania 95124, Italy
,
Massimo Libra University of Catania, Department of Biological Sciences, Via Androne 83, Catania 95124, Italy
,
Alberto M Martelli University of Bologna, Department of Human Anatomical Sciences, Via Imerio 48, Bologna, Italy
,
Giuseppe Montalto University of Palermo, Department of Clinical Medicine and Emerging Pathologies, 141 Via del Vespro, Palermo 90127, Italy
&
Melchiorre Cervello Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare “Alberto Monroy”, Via Ugo La Malfa 153, Palermo 90146, Italy
 show all
Pages 633-648 | Published online: 28 Aug 2009

Bibliography

  • Steelman LS, Abrams SL, Whelan J, Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and JAK/STAT pathways to leukemia. Leukemia 2008;22:686-707
  • McCubrey JA, Steelman LS, Abrams SL, Targeting survival cascades induced by activation of Raf/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy. Leukemia 2008;22:708-22
  • McCubrey JA, Milella M, Tafuri A, Targeting the Raf/MEK/ERK pathway with small-molecule inhibitors. Curr Opin Invest Drugs 2008;9:614-30
  • McCubrey JA, Steelman LS, Chappell WH, Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochem Biophys Acta 2007;1773:1263-84
  • Ciuffreda L, McCubrey JA, Milella M. Cytoplasmic signaling intermediates (PI3K/PTEN/Akt/mTOR and Raf/MEK/ERK pathways as therapeutic targets for anti-cancer and anti-angiogenesis treatments. Curr Signal Transduct Ther 2009. In Press
  • Avruch J. MAP kinase pathways: the first twenty years. Biochem Biophys Acta 2007;1773:1150-61
  • Zebisch A, Troppmair J. Back to the roots: the remarkable RAF oncogene story. Cell Mol Life Sci 2006;63:1314-30
  • Zebisch A, Czernilofsky AP, Keri G, Signaling through RAS-RAF-MEK-ERK: from basics to bedside. Curr Med Chem 2007;14:601-23
  • Rajalingam K, Schreck R, Rapp UR, S. Ras oncogenes and their downstream targets. Biochem Biophys Acta 2007;1773:1177-96
  • Balan V, Leicht DT, Zhu J, Identification of novel in vivo Raf-1 phosphorylation sites mediating positive feedback Raf-1 regulation by extracellular signal-regulated kinase. Mol Biol Cell 2006;17:1141-53
  • Dougherty MK, Muller J, Ritt DA, Regulation of Raf-1 by direct feedback phosphorylation. Mol Cell 2005;17:215-24
  • Brummer T, Naegele H, Reth M, Identification of novel ERK-mediated feedback phosphorylation sites at the C-terminus of B-Raf. Oncogene 2003;22:8823-34
  • Catalanotti F, Reyes G, Jesenberger V, A Mek1-Mek2 heterodimer determines the strength and duration of the Erk signal. Nat Struct Mol Biol 2009;16:294-303
  • Blalock WL, Navolanic PM, Steelman LS, Requirement for the PI3K/Akt pathway in MEK1-mediated growth and prevention of apoptosis: identification of an achilles heel in leukemia. Leukemia 2003;17:1058-67
  • Deng X, Kornblau SM, Ruvolo PP, Regulation of Bcl2 phosphorylation and potential significance for leukemic cell chemoresistance. J Natl Cancer Inst Monogr 2001;28:30-7
  • Carter BZ, Milella M, Tsao T, Regulation and targeting of antiapoptotic XIAP in acute myeloid leukemia. Leukemia 2003;17:2081-89
  • O'Neill E, Rushworth L, Baccarini M, Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene Raf. Science 2004;306:2267-70
  • O'Neill EE, Matallanas D, Kolch W. Mammalian sterile 20-like kinases in tumor suppression: An emerging pathway. Cancer Res 2005;65:5485-87
  • Deng X, Gao F, Flagg T, Mono- and multisite phosphorylation enhances Bcl-2's antiapoptotic function and inhibition of cell cycle entry. Proc Natl Acad Sci USA 2004;101:153-8
  • Deng X, Gao F, May WS. Protein phosphatase 2A inactivates Bcl2's antiapoptotic function by dephosphorylaation and up-regulation of Bcl2-p53 binding. Blood 2009;113:422-8
  • Xin M, Gao F, May WS, Protein kinase Czeta abrogates the proapoptotic function of Bax through phosphorylation. J Biol Chem 2007;282:21268-77
  • Xin M, Deng X. Protein phosphatase 2A enhances the proapoptotic function of Bax through dephosphorylation. J Biol Chem 2006;281:18859-67
  • Ruvolo VR, Kurinna SM, Karanjeet KB, PKR regulates B56(alpha)-mediated BCL2 phosphatase activity in acute lymphoblastic leukemia-derived REH cells. J Biol Chem 2008;283:35474-85
  • Deng X, Gao F, Flagg T, Bcl2's flexible loop domain regulates p53 binding and survival. Mol Cell Biol 2006;26:4421-34
  • Flotho S, Valcamonica S, Mach-Pascual G, RAS mutations and clonality analysis in children with juvenile myelomonocytic leukemia (JMML). Leukemia 1999;13:32-7
  • Li W, Zhu T, Guan KL. Transformation potential of Ras isoforms correlates with activation of phosphatidylinositol 3-kinase but not ERK. J Biol Chem 2004;279:37398-406
  • Inder K, Harding A, Plowman SJ, Activation of the MAPK module from different spatial locations generates distinct system outputs. Mol Biol Cell 2008;19:4776-84
  • Goel V, Lazar AJF, Warneke CL, Examination of mutations in B-Raf, N-Ras and PTEN in primary cutataneous melanoma. J Inv Dermatol 2005;126:154-60
  • Dahl C, Guidberg P. The genome and epigenome of malignant melanoma. APMIS 2007;115:1161-76
  • Tannapfel A, Sommerer F, Benicke M, Mutations of the BRAF gene in cholangiocarcinoma but not in hepatocellular carcinoma. Gut 2003;52:706-12
  • Garnett MJ, Marais R. Guilty as charged: B-Raf is a human oncogene. Cancer Cell 2004;6:313-9
  • Davies H, Bignell GR, Cox C, Mutations of the BRAF gene in human cancer. Nature 2002;417:949-54
  • Dhomen N, Marais R. BRAF signaling and targeted therapies in melanoma. Hematol Oncol Clin N Am 2009;23:529-45
  • Wan PT, Garnett MJ, Roe SM, Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 2004;116:855-67
  • Zebisch A, Staber PB, Delavar A, Two transforming C-RAF germ-line mutations identified in patients with therapy-related acute myeloid leukemia. Cancer Res 2006;166:3401-8
  • Zebisch A, Haller M, Hiden K, Loss of Raf kinase inhibitor protein is a somatic event in the pathogenesis of therapy-related acute myeloid leukemias with C-RAF germline mutations. Leukemia 2009;23:1049-53
  • Buscà R, Abbe P, Mantoux F, Ras mediates the cAMP-dependent activation of extracellular signal-regulated in melanocytes. EMBO J 2000;19:2900-10
  • Garnett MJ, Rana S, Paterson H, Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization. Mol Cell 2005;20:963-9
  • Rushworth LK, Hindley AD, O'Neill E, Regulation and role of Raf-1/B-Raf heterodimerization. Mol Cell Biol 2006;26:2262-72
  • Yuen ST, Davies H, Chan TL, Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia. Cancer Res 2002;62:6451-55
  • Sidera K, Patsavoudi E. Extracellular Hsp90: conquering the cell surface. Cell Cycle 2008;7:1564-8
  • Karpanagiotou EM, Syrigos K, Saif MW. Heatshock protein inhibitors and vaccines as new agent in cancer treatment. Expert Opin Investig Drug 2009;18:161-74
  • Kornblau SM, Womble M, Qiu YH, Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia. Blood 2006;108:2358-65
  • Shelton JG, Steelman LS, Abrams SL, The epidermal growth factor receptor gene family as a target for therapeutic intervention in numerous cancers: What's genetics got to do with it? Expert Opin Ther Targets 2005;9:1009-30
  • Lynch TJ, Bell DW, Sordella R, Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-39
  • Pao W, Wang TY, Riely GJ, KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005;2:57-61
  • Sequist LV, Haber DA, Lynch TJ. Epidermal growth factor receptor mutations in non-small cell lung cancer: predicting clinical response to kinase inhibitors. Clin Cancer Res 2005;11:5668-70
  • King AJ, Patrick DR, Batorsky RS, Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res 2006;66:11100-5
  • Flaherty K, Puzanov J, Sosman K, Phase I study of PLX4032: proof of concept for V600E BRAF mutation as a therapeutic target in human cancer. J Clin Oncol 2009;25:15s
  • Tsai J, Lee JT, Wang W, Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci USA 2008;105:3041-6
  • Solit DB, Garraway LA, Pratilas CA, BRAF mutation predicts sensitivity to MEK inhibition. Nature 2006;439:358-62
  • Misaghian N, Ligresti G, Steelman LS, Targeting the leukemic stem sell—the holy grail of leukemia therapy. Leukemia 2009;23:25-42
  • Barnes G, Bulusu VR, Hardwick RH, A review of the surgical management of metastatic gastrointestinal stromal tumours (GISTs) on imatinib mesylate (Glivec trade mark). Int J Surg 2005;3:206-12
  • Khazek V, Astsaturov I, Serebriiski IG, Selective Raf inhibition in cancer therapy. Expert Opin Ther Target 2007;11:1587-609
  • Shelton JG, Moye PW, Steelman LS, Differential effects of kinase cascade inhibitors on neoplastic and cytokine-mediated cell proliferation. Leukemia 2003;17:1765-82
  • Schwartz GK, Robertson S, Shen A, A phase I study of XL281, a selective oral Raf kinase inhibitor in patients with advanced solid tumors. J Clin Oncol 2009;27:3513
  • Lyons JF, Wilhelm S, Hibner B, Discovery of a novel Raf kinase inhibitor. Endocr Relat Cancer 2001;8:219-25
  • Wilhelm SM, Carter C, Tang LY, 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;64:7099-109
  • Sharma A, Trivedi NR, Zimmerman MA, Mutant V599E B-Raf regulates growth and vascular development of malignant melanoma tumors. Cancer Res 2005;65:2412-21
  • Sharma A, Tran MA, Liang S, Targeting mitogen-activated protein kinase/extracellular signal-regulated kinase kinase in the mutant (V600E) B-Raf signaling cascade effectively inhibits melanoma lung metastases. Cancer Res 2006;66:8200-09
  • Sebolt-Leopold JS. Advances in the development of cancer therapeutics directed against the Ras-mitogen-activated protein kinase pathway. Clin Cancer Res 2008;14:3651-56
  • Smalley KSM, Flaherty KT. Integrating BRAF/MEK inhibitors into combination therapy for melanoma. Br J Cancer 2009;100:431-5
  • Rimassa L, Santoro A. Sorafenib therapy in advanced hepatocellular carcinoma: the SHARP trial. Expert Rev Anticancer Ther 2009;9:739-45
  • Ouyang B, Knauf JA, Smith EP, Inhibitors of Raf kinase activity block growth of thyroid cancer cells with RET/PTC or BRAF mutations in vitro and in vivo. Clin Cancer Res 2006;12:1785-93
  • Sathornsumette S, Hgelmeland AB, Keir ST, AAL881, a novel small molecular inhibitor of Raf and vascular endothelial growth factor receptor activities, blocks the growth of malignant glioma. Cancer Res 2006;66:8722-30
  • Nagy A, Balint I, Kovacs G. Frequent allelic changes at chromosome 7q34 but lack of mutation of the BRAF in papillary renal cell tumors. Int J Cancer 2003;106:980-1
  • Karasarides M, Chiloeches A, Hayward R, B-RAF is a therapeutic target in melanoma. Oncogene 2004;23:6292-8
  • Montalto G, Cervello M, Giannitrapani L, Epidemiology, risk factors, and natural history of hepatocellular carcinoma. Ann NY Acad Sci 2002;963:13-20
  • Parkin DM, Bary F, Ferlay J, Global cancer statistics 2002. CA Cancer J Clin 2005;55:74-108
  • Llovet JM, Ricci S, Mazzaferro V, Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-90
  • El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557-76
  • El-Serag HB. Hepatocellular carcinoma: recent trends in the United States. Gastroenterology 2004;127:S27-34
  • Regimbeau JM, Colombat M, Mognol P, Obesity and diabetes as a risk factor for hepatocellular carcinoma. Liver Transpl 2004;10:S69-73
  • Moller H, Mellemgaard A, Lindvig K, Obesity and cancer risk: a Danish record-linkage study. Eur J Cancer 1994;30:344-50
  • Schmidt CM, McKillop IH, Cahill PA, Increased MAPK expression and activity in primary human hepatocellular carcinoma. Biochem Biophys Res Commun 1997;236:54-8
  • Huynh H, Nguyen TT, Chow KH, Over-expression of the mitogen-activated protein kinase (MAPK) kinase (MEK)–MAPK in hepatocellular carcinoma: its role in tumor progression and apoptosis. BMC Gastroenterol 2003;3:19
  • Ito Y, Sasaki Y, Horimoto M, Activation of mitogen-activated protein kinases/extracellular signal-regulated kinases in human hepatocellular carcinoma. Hepatology 1998;27:951-8
  • Tanimura S, Chatani Y, Hoshino R, Activation of the 41/43 kDa mitogen-activated protein kinase signaling pathway is required for hepatocyte growth factor-induced cell scattering. Oncogene 1998;17:57-65
  • Tsuboi Y, Ichida T, Sugitani S, Overexpression of extracellular signal–regulated protein kinase and its correlation with proliferation in human hepatocellular carcinoma. Liver Int 2004;24:432-6
  • Calvisi DF, Ladu S, Gorden A, Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology 2006;130:1117-28
  • Fong CW, Chua MS, McKie AB, Sprouty 2, an inhibitor of mitogen-activated protein kinase signaling, is down-regulated in hepatocellular carcinoma. Cancer Res 2006;66:2048-58
  • Yoshida T, Hisamoto T, Akiba J, Spreds, inhibitors of the Ras/ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumors. Oncogene 2006;25:6056-66
  • Lee HC, Tian B, Sedivy JM, Loss of Raf kinase inhibitor protein promotes cell proliferation and migration of human hepatoma cells. Gastroenterology 2006;131:1208-17
  • Schuierer MM, Bataille F, Weiss TS, Raf kinase inhibitor protein is downregulated in hepatocellular carcinoma. Oncol Rep 2006;16:451-6
  • Molhoek KR, Brautigan DL, Slingluff CLJr. Synergistic inhibition of human melanoma proliferation by combination treatment with B-Raf inhibitor BAY43-9006 and mTOR inhibitor rapamycin. J Transl Med 2003;3:39
  • Wang Z, Zhou J, Fan J, Effects of rapamycin alone and in combination with sorafenib in an orthotopic model of human hepatocellular carcinoma. Clin Cancer Res 2008;14:5124-30
  • Adjei AA, Molina JR, Mandrekar S, Phase I trial of sorafenib in combination with gefitinib in patients with refractory or recurrent non-small-cell lung cancer. Clin Cancer Res 2007;13:2684-91
  • Andrieux LO, Fautrei A, Bessard A, GATA-1 is essential in EGF-meditated induction of nucleotide excision repair activity and ERCCI expression through ERK2 in human hepatoma cells. Cancer Res 2007;67:2114-23
  • Abou-Alfa G, Hohnson P, Knox J. Preliminary results from a phase II, randomized, double-blind study of sorafenib plus doxorubicin versus placebo plus doxorubicin in patients with advanced hepatocellular carcinoma. Eur J Cancer Suppl 2007;5:259
  • Abou-Alfa GK, Johnson P, Knox J, et al. Final results from a phase II (PhII), randomized, double-blind study of sorafenib plus doxorubicin (S+D) versus placebo plus doxorubicin (P+D) in patients (pts) with advanced hepatocellular carcinoma (AHCC) [abstract 128]. ASCO 2008 Gastrointestinal Cancers Symposium
  • Lampiasi N, Azzolina A, D'Alessandro N, Antitumor effects of DHMEQ, a novel NF-kappaB inhibitor, in human liver cancer cells through reactive oxygen species-dependent mechanism. Mol Pharmacol 2009;76:290-300
  • Montagut C, Sharma SV, Shioda T, Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma. Cancer Res 2008;4853-61
  • Smalley KSM, Lioni M, Dalla Palma M, Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas. Mol Cancer Ther 2008;7:2876-83
  • Sosman JA, Puzanov I, Atkins MB. Opportunities and obstacles to combination targeted therapy in renal cell cancer. Clin Cancer Res 2007;13:764s-9s
  • Siu LL, Awada A, Takimoto CH, Phase I trial of Sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer. Clin Cancer Res 2006;12:144-51

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