Farnesyl transferase inhibitors in myeloid malignancies

Blood Reviews

Volumn 17, Issue 3, 2003, Pages 123-129

  Lancet, Jeffrey E ^a   Karp, Judith E ^b  

^a UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^b JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

Farnesyl transferase inhibitors; Myeloid malignancies; Ras; Signal transduction

Indexed keywords

3 BENZYL 7 CYANO 2,3,4,5 TETRAHYDRO 1 (1H IMIDAZOL 4 YLMETHYL) 4 (2 THIENYLSULFONYL) 1H 1,4 BENZODIAZEPINE; 7-CYANO-2,3,4,5-TETRAHYDRO-1-(1H-IMIDAZOL-4-YLMETHYL)-3-(PHENYLMETHYL)-4-(2-THIENYLSULFONYL)-1H-1,4-BENZODIAZEPINE; ANTINEOPLASTIC AGENT; BENZODIAZEPINE DERIVATIVE; ENZYME INHIBITOR; FARNESYL TRANS TRANSFERASE; IMATINIB; IMIDAZOLE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; PROTEIN KINASE B; PYRIMIDINE DERIVATIVE; QUINOLONE DERIVATIVE; RAS PROTEIN; TIPIFARNIB; TRANSFERASE; UNCLASSIFIED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; BIOLOGICAL MODEL; BLOOD DISEASE; BLOOD TOXICITY; BONE MARROW SUPPRESSION; BRAIN DISEASE; CELL PROLIFERATION; CELL SURVIVAL; CLINICAL TRIAL; ENZYME ACTIVITY; FATIGUE; GENE OVEREXPRESSION; HEMATOLOGIC MALIGNANCY; HUMAN; HYPERBILIRUBINEMIA; LIVER TOXICITY; METABOLISM; MYELOID LEUKEMIA; MYELOPROLIFERATIVE DISORDER; NEUROTOXICITY; ONCOGENE RAS; PERIPHERAL NEUROPATHY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RASH; REVIEW; SIGNAL TRANSDUCTION;

EID: 0037699302     PISSN: 0268960X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0268-960X(03)00008-0     Document Type: Review

References (69)

1. Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001; 344: 1038-1042.
2. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001; 344: 1031-1037.
3. Talpaz M, Silver RT, Druker BJ, Goldman JM, Gambacorti-Passerini C, Guilhot F et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood 2002; 99: 1928-1937.
4. End DW. Farnesyl protein transferase inhibitors and other therapies targeting the Ras signal transduction pathway. Invest New Drugs 1999; 17: 241-258.
5. Rowinsky EK, Windle JJ, Von Hoff DD. Ras protein farnesyltransferase: a strategic target for anticancer therapeutic development. J Clin Oncol 1999; 17: 3631-3652.
6. Boguski MS, McCormick F. Proteins regulating Ras and its relatives. Nature 1993; 366: 643-654.
7. Lowy DR, Willumsen BM. Function and regulation of ras. Annu Rev Biochem 1993; 62: 851-891.
8. Khosravi-Far R, Cox AD, Kato K, Der CJ. Protein prenylation: key to ras function and cancer intervention? Cell Growth Differ 1992; 3: 461-469.
9. Prendergast GC. Farnesyltransferase inhibitors: antineoplastic mechanism and clinical prospects. Curr Opin Cell Biol 2000; 12: 166-173.
10. Du W, Lebowitz PF, Prendergast GC. Cell growth inhibition by farnesyltransferase inhibitors is mediated by gain of geranylgeranylated RhoB. Mol Cell Biol 1999; 19: 1831-1840.
11. End DW, Smets G, Todd AV, Applegate TL, Fuery CJ, Angibaud P et al. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R1 15777 in vivo and in vitro. Cancer Res 2001; 61: 131-137.
12. James G, Goldstein JL, Brown MS. Resistance of K-RasBV12 proteins to farnesyltransferase inhibitors in Rat1 cells. Proc Natl Acad Sci USA 1996; 93: 4454-4458.
13. James GL, Goldstein JL, Brown MS, Rawson TE, Somers TC, McDowell RS et al. Benzodiazepine peptidomimetics: potent inhibitors of Ras farnesylation in animal cells. Science 1993; 260: 1937-1942.
14. Kohl NE, Wilson FR, Mosser SD, Giuliani E, deSolms SJ, Conner MW et al. Protein farnesyltransferase inhibitors block the growth of ras-dependent tumors in nude mice. Proc Natl Acad Sci USA 1994; 91: 9141-9145.
15. Kohl NE, Mosser SD, deSolms SJ, Giuliani EA, Pompliano DL, Graham SL et al. Selective inhibition of ras-dependent transformation by a farnesyltransferase inhibitor. Science 1993; 260: 1934-1937.
16. Liu M, Bryant MS, Chen J, Lee S, Yaremko B, Lipari P et al. Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res 1998; 58: 4947-4956.
17. Mahgoub N, Taylor BR, Gratiot M, Kohl NE, Gibbs JB, Jacks T et al. In vitro and in vivo effects of a farnesyltransferase inhibitor on Nf1-deficient hematopoietic cells. Blood 1999; 94: 2469-2476.
18. Nagasu T, Yoshimatsu K, Rowell C, Lewis MD, Garcia AM. Inhibition of human tumor xenograft growth by treatment with the farnesyl transferase inhibitor B956. Cancer Res 1995; 55: 5310-5314.
19. Prendergast GC, Davide JP, deSolms SJ, Giuliani EA, Graham SL, Gibbs JB et al. Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton. Mol Cell Biol 1994; 14: 4193-4202.
20. Sepp-Lorenzino L, Ma Z, Rands E, Kohl NE, Gibbs JB, Oliff A et al. A peptidomimetic inhibitor of farnesylprotein transferase blocks the anchorage-dependent and -independent growth of human tumor cell lines. Cancer Res 1995; 55: 5302-5309.
21. Kohl NE, Omer CA, Conner MW, Anthony NJ, Davide JP, deSolms SJ et al. Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice. Nat Med 1995; 1: 792-797.
22. Whyte DB, Kirschemeier P, Hockenberry TN, Nunez-Oliva I, James L, Catino JJ et al. K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. J Biol Chem 1997; 272: 14459-14464.
23. Du W, Liu A, Prendergast GC. Activation of the P13'K-AKT pathway masks the proapoptotic effects of farnesyltransferase inhibitors. Cancer Res 1999; 59: 4208-4212.
24. Sawyers CL, McLaughlin J, Witte ON. Genetic requirement for Ras in the transformation of fibroblasts and hematopoietic cells by the Bcr-Abl oncogene. J Exp Med 1995; 181: 307-313.
25. Shurin MR, Esche C, Lotze MT. FLT3: receptor and ligand. Biology and potential clinical application. Cytokine Growth Factor Rev 1998; 9: 37-48.
26. Schnittger S, Schoch C, Dugas M, Kern W, Staib P, Wuchter C et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood 2002; 100: 59-66.
27. Thiede C, Steudel C, Mohr B, Schaich M, Schakel U, Platzbecker U et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 2002; 99: 4326-4335.
28. Stirewalt DL, Kopecky KJ, Meshinchi S, Appelbaum FR, Slovak ML, Willman CL et al. FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood 2001; 97: 3589-3595.
29. Mizuki M, Fenski R, Halfter H, Matsumura I, Schmidt R, Muller C et al. Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways. Blood 2000; 96: 3907-3914.
30. Hayakawa F, Towatari M, Kiyoi H, Tanimoto M, Kitamura T, Saito H et al. Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene 2000; 19: 624-631.
31. Davis RJ. Transcriptional regulation by MAP kinases. Mol Reprod Dev 1995; 42: 459-467.
32. Dent P, Haser W, Haystead TA, Vincent LA, Roberts TM, Sturgill TW. Activation of mitogen-activated protein kinase kinase by v-Raf in NIH 3T3 cells and in vitro. Science 1992; 257: 1404-1407.
33. Kyriakis JM, App H, Zhang XF, Baneriee P, Brautigan DL, Rapp UR et al. Raf-1 activates MAP kinase-kinase. Nature 1992; 358: 417-421.
34. Robbins DJ, Zhen E, Owaki H, Vanderbilt CA, Ebert D, Geppert TD et al. Regulation and properties of extracellular signal-regulated protein kinases 1 and 2 in vitro. J Biol Chem 1993; 268: 5097-5106.
35. Xing J, Ginty DD, Greenberg ME. Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science 1996; 273: 959-963.
36. Downward J. Mechanisms and consequences of activation of protein kinase B/Akt. Curr Opin Cell Biol 1998; 10: 262-267.
37. Duronio V, Scheid MP, Ettinger S. Downstream signalling events regulated by phosphatidylinositol 3-kinase activity. Cell Signal 1998; 10: 233-239.
38. Marte BM, Downward J. PKB/Akt: connecting phosphoinositide 3-kinase to cell survival and beyond. Trends Biochem Sci 1997; 22: 355-358.
39. Kinoshita T, Shirouzu M, Kamiya A, Hashimoto K, Shigeyuki Y, Miyajima A. Raf/MAPK and rapamycin-sensitive pathways mediate the anti-apoptotic function of p21 Ras in IL-3-dependent hematopoietic cells. Oncogene 1997; 15: 619-627.
40. Alessi DR, Cuenda A, Cohen P, Dudley DT, Saltiel AR. PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. J Biol Chem 1995; 270: 27489-27494.
41. Skorski T, Bellacosa A, Nieborowska-Skorska M, Majewski M, Martinez R, Choi JK et al. Transformation of hematopoietic cells by BCR/ABL requires activation of a PI-3k/Akt dependent pathway. EMBO J 1997; 16: 6151-6161.
42. Kiyoi H, Naoe T, Nakano Y, Yokota T, Minami S, Miyawaki S et al. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood 1999; 93: 3074-3080.
43. Lee YY, Kim WS, Bang YJ, Jung CW, Park S, Yoon WJ et al. Analysis of mutations of neurofibromatosis type 1 gene and N-ras gene in acute myelogenous leukemia. Stem Cells 1995; 13: 556-563.
44. Neubauer A, Dodge RK, George SL, Davey FR, Silver RT, Schiffer CA et al. Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia. Blood 1994; 83:1603-1611.
45. Padua RA, Guinn BA, al-Sabah AI, Smith M, Taylor C, Pettersson T et al. RAS, FMS, and p53 mutations and poor clinical outcome in myelodysplasias: a 10 year follow-up. Leukemia 1998; 12: 887-892.
46. Paquette RL, Landaw EM, Pierre RV, Kahan J, Lubbert M, Lazcano O et al. N-ras mutations are associated with poor prognosis and increased risk of leukemia in myelodysplastic syndrome. Blood 1993; 82: 590-599.
47. Radich JP, Kopecky KJ, Willman CL, Weick J, Head D, Appelbaum F et al. N-ras mutations in adult de novo acute myelogenous leukemia: prevalence and clinical significance. Blood 1990; 76: 801-807.
48. Kim SC, Hahn JS, Min YH, Yoo NC, Ko YW, Lee WJ. Constitutive activation of extracellular signal-regulated kinase in human acute leukemias: combined role of activation of MEK, hyperexpression of extracellular signal-regulated kinase, and downregulation of a phosphatase, PACI. Blood 1999; 93: 3893-3899.
49. Kornblau SM, Milella M, Ball G, Qui YH, Ruvolo P, Estrov Z et al. ERK2 and Phospho-ERK2 are prognostic for survival in AML and complement the prognostic impact of Bax and BCL-2. Blood 2001; 98: 716a, Abstract.
50. Towatari M, Iida H, Iwata H, Hamaguchi M, Saito H. Constitutive activation of mitogen-activated protein kinase pathway in acute leukemia cells. Leukemia 1997; 11: 479-484.
51. Lancet JE, Ryan CP, Abboud CN, Rosell KE, Lu C, Karp JE et al. Differences in the expression of signal transduction molecules between normal and leukemic bone marrow. Blood 2002; 98: 111a, Abstract.
52. Lancet JE, Willman CL, Bennett JM. Acute myelogenous leukemia and aging: clinical interactions. Hematol Oncol Clin North Am 2000; 14: 251-267.
53. Lowenberg B, Suciu S, Archimbaud E, Ossenkoppele G, Verhoef GE, Vellenga E et al. Use of recombinant GM-CSF during and after remission induction chemotherapy in patients aged 61 years and older with acute myeloid leukemia: final report of AML-II, a phase III randomized study of the Leukemia Cooperative Group of European Organisation for the Research and Treatment of Cancer and the Dutch Belgian Hemato-Oncology Cooperative Group. Blood 1997; 90: 2952-2961.
54. Godwin JE, Kopecky KJ, Head DR, Willman CL, Leith CP, Hynes HE et al. A double-blind placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: a Southwest oncology group study (9031). Blood 1998; 91: 3607-3615.
55. Dombret H, Chastang C, Fenaux P, Reiffers J, Bordessoule D, Bouabdallah R et al. A controlled study of recombinant human granulocyte colony-stimulating factor in elderly patients after treatment for acute myelogenous leukemia. AML Cooperative Study Group. N Engl J Med 1995; 332: 1678-1683.
56. Feldman EJ, Seiter K, Damon L, Linker C, Rugo H, Ries C et al. A randomized trial of high- vs standard-dose mitoxantrone with cytarabine in elderly patients with acute myeloid leukemia. Leukemia 1997; 11: 485-489.
57. Leith CP, Kopecky KJ, Chen IM, Eijdems L, Slovak ML, McConnell TS et al. Frequency and clinical significance of the expression of the multidrug resistance proteins MDRI/P-glycoprotein, MRPI, and LRP in acute myeloid leukemia: a Southwest Oncology Group Study. Blood 1999; 94: 1086-1099.
58. Leith CP, Kopecky KJ, Godwin J, McConnell T, Slovak ML, Chen IM et al. Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDRI) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study. Blood 1997; 89: 3323-3329.
59. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079-2088.
60. Karp JE, Lancet JE, Kaufmann SH, End DW, Wright JJ, Bol K et al. Clinical and biologic activity of the farnesyltransferase inhibitor R1 15777 in adults with refractory and relapsed acute leukemias: a phase I clinical-correlative trial. Blood 2001; 97: 3361-3369.
61. Harousseau J-L, Stone R, Thomas X, Lancet J, Arani R, Thibault A et al. Interim results from a phase II study of R1 15777 (ZARNESTRA) in patients with refractory and relapsed acute myelogenous leukemia. Progr/Proc Am Soc Clin Oncol 2002; 21: 265a, Abstract.
62. Raponi M, Belly R, Atkins D, Thibault A, Rackoff W, Rybak ME et al. Pharmacogenomic analysis reveals signaling pathways modulated by R1 15777 (Zarnestra) in acute myeloid leukemia. Prog/Proc Am Soc Clin Oncol 2002; 21: 265a, Abstract.
63. Lancet JE, Karp JE, Gotlib J, Kaufmann SH, Gojo I, Greenberg PL et al. Zarnestra (R1 15777) in previously untreated poor-risk AML and MDS: preliminary results of a phase II trial. Blood 2002; 100: 560a.
64. Kurzrock R, Sebti Sm, Kantarjian HM, Wright J, Cortes JE, Thomas DA et al. Phase I study of a farnesyl transferase inhibitor, R1 15777, in patients with myelodysplastic syndromes. Blood 2001; 98: 623a, Abstract.
65. Kurzrock R, Cortes J, Rybak ME, Thibault A, Faderl S, Estey E et al. Phase II study of R1 15777, a farnesyltransferase inhibitor, in myelodysplastic syndrome. Blood 2001; 98: 848a, Abstract.
66. Thomas D, Cortes J, O'Brien SM, Garcia Manero G, Kurzrock R, Giles FJ et al. R1 15777, a farnesyltransferase inhibitor (FTI), has significant anti-leukemia activity in patients with chronic myeloid leukemia (CML). Blood 2001; 98: 727a, Abstract
67. Gotlib J, Dugan K, Katamneni U, Sridhar K, Wright J, Thibault A et al. Phase I/II study of farnesyltransferase inhibitor R1 15777 (Zarnestra) in patients with myeloproliferative disorders (MPDs): preliminary results. J Clin Oncol 2002; 21: 4a, Abstract.
68. Cortes J, Kurzrock R, O'Brien SM, Thomas D, Faderl S, Garcia-Manero G et al. Phase I study of a farnesyl transferase inhibitor (FTI), BMS-214662, in patients with refractory or relapsed acute leukemias. Blood 2002; 98: 594a, Abstract.
69. Hoover RR, Mahon FX, Melo JV, Daley GQ. Overcoming ST1571 resistance with the farnesyl transferase inhibitor SCH66336. Blood 2002; 100: 1068-1071.