Farnesyltransferase inhibitors: Preliminary results in acute myeloid leukemia;Inhibiteurs de farnésyl transférase: Résultats cliniques dans la leucémie aiguë myéloïde

Bulletin du Cancer

Volumn 92, Issue 3, 2005, Pages 227-238

  Thomas, Xavier ^a   Elhamri, Mohamed ^a  

^a EDOUARD HERRIOT HOSPITAL   (France)

Author keywords

Acute myeloid leukemia; Farnesyltransferase inhibitors; Myelodysplasia; 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; BMS 184467; BMS 185878; BMS 186511; FT 1276; L 371735; L 731735; L 778123; LONAFARNIB; N (8 AMINO 2 BENZYL 5 ISOPROPYL 9 MERCAPTO 3,6 NONADIENOYL)METHIONINE; PEPTIDE DERIVATIVE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; R 11577; TIPIFARNIB; UNCLASSIFIED DRUG; 7-CYANO-2,3,4,5-TETRAHYDRO-1-(1H-IMIDAZOL-4-YLMETHYL)-3-(PHENYLMETHYL)-4-(2-THIENYLSULFONYL)-1H-1,4-BENZODIAZEPINE; AKT1 PROTEIN, HUMAN; BENZODIAZEPINE DERIVATIVE; ENZYME INHIBITOR; FARNESYL TRANS TRANSFERASE; IMIDAZOLE DERIVATIVE; L 778,123; MITOGEN ACTIVATED PROTEIN KINASE 1; ONCOPROTEIN; PIPERIDINE DERIVATIVE; PROTEIN KINASE B; PROTEIN SERINE THREONINE KINASE; PYRIDINE DERIVATIVE; QUINOLONE DERIVATIVE; RAS PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; TRANSFERASE;

ACUTE GRANULOCYTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; ASTHENIA; BLOOD TOXICITY; CANCER INHIBITION; CARDIOTOXICITY; CELL PROLIFERATION; CELL SURVIVAL; CLINICAL TRIAL; DISEASE MODEL; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; ENZYME ACTIVITY; ENZYME INHIBITION; FEVER; HUMAN; MYELODYSPLASIA; NAUSEA; NEPHROTOXICITY; NEUROTOXICITY; NONHUMAN; PHENOTYPE; PRENYLATION; REVIEW; SIGNAL TRANSDUCTION; VOMITING; DRUG ANTAGONISM; DRUG RESISTANCE; ENZYMOLOGY; METABOLISM; MYELOPROLIFERATIVE DISORDER; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PROTEIN PROCESSING;

ALKYL AND ARYL TRANSFERASES; BENZODIAZEPINES; CLINICAL TRIALS, PHASE I; CLINICAL TRIALS, PHASE II; DRUG RESISTANCE, NEOPLASM; ENZYME INHIBITORS; FARNESYLTRANSTRANSFERASE; HUMANS; IMIDAZOLES; LEUKEMIA, MYELOCYTIC, ACUTE; MITOGEN-ACTIVATED PROTEIN KINASE 1; MYELOPROLIFERATIVE DISORDERS; PIPERIDINES; PROTEIN ISOPRENYLATION; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; PYRIDINES; QUINOLONES; RAS PROTEINS; RHO GTP-BINDING PROTEINS;

EID: 17144393248     PISSN: 00074551     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (111)

1. Thomas X, Belhabri A. Leucémies aiguës myéloïdes du sujet âgé: mise au point. Bull Cancer 2001; 88: 143-54.
2. Geller RB, Burke PJ, Karp JE, Humphrey RL, Braine HG, Tucker RW, et al. A two-step timed sequential treatment for acute myelogenous leukemia. Blood 1989; 74: 1499-506.
3. Baudard M, Beauchamp-Nicoud A, Delmer A, Rio B, Blanc C, Zittoun R, et al. Has the prognosis of adult patients with acute myeloid leukemia improved over years? A single institution experience of 784 consecutive patients over a 16-year period. Leukemia 1999; 13: 1481-90.
4. Hiddemann W, Kern W, Schoch C, Fonatsch C, Heinecke A, Wormann B, et al. Management of acute myeloid leukemia in elderly patients. J Clin Oncol 1999; 17: 3569-76.
5. Thomas X, Le QH. Traitement des leucémies aiguës myéloïdes de l'adulte en rechute. Bull Cancer 2002; 89: 795-807.
6. McCubrey JA, May WS, Duriono V, Mufson A. Serine/threonine phosphorylation in cytokine signal transduction. Leukemia 2000; 14: 9-21.
7. Rebollo A, Martinez AC. Ras proteins: recent advances and new functions. Blood 1999; 94: 2971-80.
8. 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: 1038-42.
9. Reuter CWM, Morgan MA, Bergmann L. Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematological malignancies? Blood 2000; 96: 1655-69.
10. Hahn SM, Bernhard E, McKenna WG. Farnesyltransferase inhibitors. Semin Oncol 2001; 28: 86-93.
11. 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: 590-9.
12. 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: 1603-11.
13. Thorn J, Molloy P, Iland H. SSCP detection of N-Ras promotor mutations in AML patients. Exp Hematol 1995; 23: 1098-103.
14. Byrne JL, Marshall CJ. The molecular pathophysiology of myeloid leukaemias: Ras revisited. Br J Haematol 1998; 100: 256-64.
15. Rowansky EK, Windle JJ, Von Hoff DD. Ras protein farnesyltransferase: A strategic target for anticancer therapeutic development. J Clin Oncol 1999; 17: 3631-52.
16. Boguski MS, McCormick F. Proteins regulating Ras and its relatives. Nature 1993; 366: 643-54.
17. Lowy DR, Willumsen BM. Function and regulation of Ras. Annu Rev Biochem 1993; 62: 851-91.
18. Sebti SM, Hamilton AD. Farnesyltransferase and geranylgeranyltransferase I inhibitors and cancer therapy: lessons from mechanism and bench-to-bedside translational studies. Oncogene 2000; 19: 6584-93.
19. Crui M, De Klerk GJ, Beijnen JH, Schellens JH. Ras biochemistry and farnesyl transferase inhibitors: a literature survey. Anticancer Drugs 2001; 12: 163-84.
20. Tamanoi F, Gau CL, Jiang C, Edarnatsu H, Kato-Stankiewiicz J. Protein farnesylation in mammalian cells: effects of farnesyltransferase inhibitors on cancer cells. Cell Mol Life Sci 2001; 58: 1636-49.
21. Lancet JE, Karp JE. Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapy. Blood 2003; 102: 3880-9.
22. Brunner TB, Hahn SM, Gupta AK, Muschel RJ, McKenna WG, Bernhard EJ. Farnesyltransferase inhibitors: An overview of the results of preclinical and clinical investigations. Cancer Res 2003; 63: 5656-68.
23. Mazieres J, Pradines A, Favre G. Perspectives on farnesyl transferase inhibitors in cancer therapy. Cancer Lett 2004; 206: 159-67.
24. Ashar HR, James L, Gray K, Carr D, Black S, Armstrong L, et al. Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules. J Biol Chem 2000; 275: 30451-7.
25. Ashar HR, James L, Gray K, Carr D, McGuirk M, Maxwell E, et al. The farnesyl transferase inhibitor SCH 66336 induces a G(2)→M or G(1) pause in sensitive human tumor cell lines. Exp Cell Res 2001; 262: 17-27.
26. Tamanoi F, Kato-Stankiewicz J, Jiang C, Machado I, Thapar N. Farnesylated proteins and cell cycle progression. J Cell Biochem 2001; 37(suppl.): 64-70.
27. End DW, Smets G, Todd AV, Applegare TL, Fuery CJ, Angibaud P, et al. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res 2001; 61: 131-7.
28. Lebowitz PF, Sakamuro D, Prendergast GC. Farnesyl transferase inhibitors induce apoptosis of Ras-transformed cells denied substratum attachment. Cancer Res 1997; 57: 708-13.
29. Liu A, Du W, Liu JP, Jessell TM, Prendergast GC. RhoB alteration is necessary for apoptotic and antineoplastic responses ro farnesyltransferase inhibitors. Mol Cell Biol 2000; 20: 6105-13.
30. Zhang B, Prendergast GC, Fenton RG. Farnesyltranferase inhibitors reverse Ras-mediated inhibition of Fas gene expression. Cancer Res 2002; 62: 4450-8.
31. Prendergast GC, Oliff A. Farnesyltransferase inhibitors: antineoplastic proporties, mechanisms of action, and clinical prospects. Semin Cancer Biol 2000; 10: 443-52.
32. Jiang K, Coppola D, Crespo NC, Nicosia SV, Hamilton AD, Sebti SM, et al. The phosphoinositide 3-OH kinase/AKT2 pathway as a critical target for farnesyltransferase inhibitor-induced apoptosis. Mol Cell Biol 2000; 20: 139-48.
33. Prevost GP, Pradines A, Viossat I, Brezak MC, Miquel K, Lonchampt MO, et al. Inhibition of human tumor cell growth in vitro and in vivo by a specific inhibitor of human farnesyltransferase: BIM-46068. Int J Cancer 1999; 83: 283-7.
34. Kohl N, Omer C, Conner M, Anthony N, Davide J, Desoms S, et al. Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in Ras transgenic mice. Nat Med 1995; 1: 792-7.
35. Rak J, Mitsuhashi Y, Bayko L, Filmus J, Shirasawa S, Sasazuki T, et al. Mutant Ras oncogenes up-regulate VEGF/VPF expression: implications for induction and inhibition of tumor angiogenesis. Cancer Res 1995; 55: 4575-80.
36. Raponi M, Belly RT, Karp JE, Lancer JE, Arkins D, Wang Y. Microarray analysis reveals genetic pathways modulated by tipifarnib in acute myeloid leukemia. BMC Cancer 2004; 4: 56.
37. Khosravi-Far R, Cox AD, Karo K, Der CJ. Protein prenylation: key to Ras function and cancer intervention? Cell Growth Differ 1992; 3: 461-9.
38. Maurer-Stroh S, Washietl S, Eisenhaber F. Protein prenyltransferases. Genome Biol 2003; 4(212): 1-9.
39. Morgan MA, Ganser A, Reuter CWM. Therapeutic efficacy of prenylation inhibitors in the treatment of myeloid leukemia. Leukemia 2003; 17: 1482-98.
40. Jackson JH, Cockran CG, Bourne JR, Solski PA, Buss JE, Der C. Farnesol modification of Kirsten Ras exon 4B protein is essential for transformation. Proc Natl Acad Sci USA 1990; 87: 3042-6.
41. Willumsen BM, Christensen A, Hubbert NL, Papageorge AG, Lowy DR. The p21 Ras C-terminus is required for transformation and membrane association. Nature 1984; 310: 583-6.
42. Chang F, Steelman LS, Lee JT, Shelton JG, Navolanic PM, Blalock WL, et al. Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention. Leukemia 2003; 17: 1263-93.
43. Steelman LS, Pohnert SC, Shelton JG, Franklin RA, Bertrand FE, McCubrey JA. JAK/STAT, Raf/MEK/ERK, P13k/Akt and BCR-ABL in cell cycle progression and leukegenesis. Leukemia 2004; 18: 189-218.
44. Hagemann C, Blank JL. The ups and downs of MEK kinase interactions. Cell Signal 2001; 13: 863-75.
45. 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: 1404-7.
46. Kyriakis JM, App H, Zhang XF, Banerjee P, Brautigan DL, Rapp VR, et al. Raf-1 activates MAP kinase-kinase. Nature 1992; 358: 417-1421.
47. Davis RJ. Transcriptional regulation by MAP kinases. Mol Reprod Dev 1995; 42: 459-67.
48. Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME, et al. Cell survival promoted by the RAS-MAPK signaling pathway by transcription- dependent and -independent mechanisms. Science 1999; 286: 1358-62.
49. Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NFκB. J Clin Invest 2001; 107: 241-6.
50. McGlynn AP, Padua RA, Burnett AK, Darley RL. Alternative effects of Ras and Raf oncogenes on the proliferation and apoptosis of factor-dependent FDC-P1 cells. Leukemia Res 2000; 24: 47-54.
51. Burgering BM, Coffer PJ. Protein kinase B (c-Akt) in phosphatidylinositol-3-kinase signal transduction. Nature 1995; 376: 599-602.
52. Klippel A, Escobedo MA, Wachowicz MS, Apell G, Brown TW, Giedlin MA, et al. Activation of phosphatidylinositol-3-kinase is sufficient for cell cycle entry and promotes cellular changes characteristic of oncogenic transformation. Mol Cell Biol 1998; 18: 5699-711.
53. Nicholson KM, Anderson NG. The protein kinase B/Akr signalling pathway in human malignancy. Cell Signal 2002; 14: 381-95.
54. Mazure NM, Chen EY, Laderoute KR, Giaccia AJ. Induction of vascular endothelial growth factor by hypoxia is modulated by a phosphatidylinositol-3- kinase/Akt signaling pathway in HaRas-transformed cells through a hypoxia inducible factor-1 transcriptional element. Blood 1997; 90: 3322-31.
55. Darta SR, Dudek H, Tao X, Masrers S, Fu H, Gotoh Y, et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997; 91: 231-41.
56. Kim AH, Khursigara G, Sun X, Franke TF, Chao MV. Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1. Mol Cell Biol 2001; 21: 893-901.
57. Ridley AJ, Hall A. The small Gtp-binding protein Rho regulates the assembly of focal adhesions and action stress fibers in response to growth factors. Cell 1992; 70: 389-99.
58. Fritz G, Just I, Kaina B. Rho GTPases are over-expressed in human tumors. Int J Cancer 1999; 81: 682-7.
59. Zalcman G, Closson V, Linares-Cruz G, Lerebours F, Honore N, Tavitian A, et al. Regulation of Ras-related RhoB protein expression during the cell-cycle. Oncogene 1995; 10: 1935-45.
60. Du W, Lebowitz PF, Prendergast GC. Cell growth inhibition by farnesyltransferase inhibitors is mediated by gain of geranylgeranylated RhoB. Mol Cell Biol 1999; 19: 1831-40.
61. Lebowitz PF, Casey PJ, Prendergast GC, Thissen JA. Farnesyltransferase inhibitors after the prenylation and growth-stimulating function of RhoB. J Biol Chem 1997; 272: 15591-4.
62. Yonemoto M, Satoh T, Arakawa H, Suzuki-Takahashi I, Monden Y, Kodera T, et al. J104,871, a novel farnesyltransferase inhibitor, blocks Ras farnesylation in vivo in a farnesyl pyrophosphate-competitive manner. Mol Pharmacol 1998; 54: 1-7.
63. Britten CD, Rowinsky EK, Soignet S, Patnaik A, Yao SL, Deutsch P, et al. A phase I and pharmacological study of the farnesyl transferase inhibitor L778,123 in patients with solid malignancies. Clin Cancer Res 2001; 7: 3894-903.
64. Manne V, Yan N, Carboni JM, Tuomari AV, Ricca CS, Brown JG, et al. Bisubstrate inhibitors of farnesyltransferase: a novel class of specific inhibitors of Ras transformed cells. Oncogene 1995; 10: 1763-79.
65. Lancet JE, Liesveld JL, Ludlow J, Rosell KF, Smith AJ, Abboud CN, et al. Effects of farnesyl transferase inhibitor R115777 on hematopesis, leukemic cell proliferation, and signaling throught the mitogen-activated protein kinase (MAPK) pathway. Blood 1999; 94(suppl 1): 149b.
66. Liu M, Bryant MS, Chen J, Lee S, Yaremko B, Lipari P, et al. Antitumor activity of SCH66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wapRas transgenic mice. Cancer Res 1998; 58: 4947-56.
67. Reichert A, Heisterkamp N, Daley GQ, Groffen J. Treatment of Bcr/Abl-positive acute lymphoblastic leukemia in P190 transgenic mice with the farnesyl transferase inhibitor SCH66336. Blood 2001; 97: 1399-403.
68. Peters DG, Hoover RR, Gerlach MJ, Koh EY, Zhang H, Choe K, et al. Activity of the farnesyl protein transferase inhibitor SCG66336 against BCR/ABL-induced murine leukemia and primary cells from patients with chronic myeloid leukemia. Blood 2001; 97: 1404-12.
69. Rose WC, Lee FY, Fairchild CR, Lynch M, Monticello T, Kramer RA, et al. Preclinical antitumor activity of BMS-214662, a highly apoptotic and novel farnesyl transferase inhibitor. Cancer Res 2001; 61: 7507-17.
70. Lobell RB, Liu D, Buser CA, Davide JP, DePuy E, Hamilton K, et al. Preclinical and clinical pharmacodynamic assessment of L778,123, a dual inhibitor of farnesyl: protein transferase and geranylgeranyl: protein transferase type-I. Mol Cancer Ther 2002; 1: 747-58.
71. Lobell RB, Omer CA, Abrams MT, Bhimnathwala HG, Brucker MJ, Buser CA, et al. Evaluation of farnesyl: protein transferase and geranylgeranyl: protein transferase inhibitor combinations in preclinical models. Cancer Res 2001; 61: 8758-68.
72. Sepp-Lorenzino L, Ma Z, Rands E, Kohl NE, Gibbs JB, Oliff A, et al. A peptidomimetic inhibitor of farnesyl protein transferase blocks the anchorage-dependent and -independent growth of human tumor cell lines. Cancer Res 1995; 55: 5302-9.
73. Reuter CW, Morgan MA, Wegner J, Ganser A. Induction of growth inhibition and apoptosis by FTase and GGTase inhibitors in myeloid leukemia cells. Blood 2002; 100(suppl. 1): 788a.
74. Morgan MA, Dolp O, Reutet CWM. Cell-cycle-dependent activation of mitogen-activated protein kinase kinase (MEK-1/2) in myeloid leukemia cell lines and induction of growth inhibition and apoptosis by inhibitors of Ras signaling. Blood 2001; 97: 1823-34.
75. Morgan MA, Wegner J, Aydilek E, Ganser A, Reuter CWM. Synergistic cytotoxic effects in myeloid leukemia cells upon cotreatment with farnesyltransferase and geranylgeranyl transferase-I inhibitors. Leukemia 2003; 17: 1508-20.
76. 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: 2469-76.
77. Karp JE, Lancet JE, Kaufmann SH, End DW, Wright JJ, Bol K, et al. Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical-laboratory correlative trial. Blood 2001; 97: 3361-9.
78. 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), BMS214662, in patients with refractory or relapsed acute leukemias. Blood 2001; 98(suppl. 1): 594a.
79. List AF, DeAngelo D, O'Brien S, Cortes J, Wilson J, Sugrue MM, et al. Phase I study of continuous oral administration of lonafarnib (Sarasar™) in patients with advanced hematologic malignancies. Blood 2002; 100(suppl. 1): 789a.
80. Ravoet C, Mineur P, Robin V, Debusscher L, Bosly A, André M, et al. Phase I-II study of a farnesyl transferase inhibitor (FTI), SCH66336, in patients with myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML). Blood 2002; 100(suppl. 1): 794a.
81. Harousseau JL, Stone R, Thomas X, Lancet J, Arani R, Thibault A, et al. Interim results from a phase II study of R115777 (Zarnestra) in patients with refractory and relapsed acute myelogenous leukemia. Proc Am Soc Clin Oncol 2002; 21: 265a.
82. Harousseau JL, Reiffers J, Löwenberg B, Thomas X, Huguet F, Fenaux P, et al. Zarnestra™ (R115777) in patients with relapsed and refractory acute myelogenous leukemia (AML): Results of a multicenter phase 2 study. Blood 2003; 102(suppl. 1): 176a.
83. Harousseau JL, Reiffers J, Löwenberg B, Thomas X, Huguet F, Fenaux P, et al. Drug exposure in a phase 2 study of patients with relapsed and refractory acute myelogenous leukemia (AML) treated with Zarnesrta (tipifarnib). Hematol J 2004; 5(suppl. 2): S34.
84. Harousseau JL, Reiffers J, Löwenberg B, Thomas X, Huguet F, Fenaux P, et al. Safety profile of Zarnestra (tipifarnib) in patients with relapsed and refractory acute myelogenous leukemia (AML). Hematol J 2004; 5(suppl. 2): S34.
85. Lancet JE, Karp JE, Gotlib J, Liesveld JL, Kaufmann SH, Gojo I, et al. Zarnestra™ (R115777) in previously untreated poor-risk AML and MDS: preliminary results of a phase II trial. Blood 2002; 100(suppl. 1): 560a.
86. Lancet JE, Gojo I, Gorlib J, Greer J, Kaufmann SH, Liesveld JL, et al. Tipifarnib (Zarnestra™) in previously untreated poor-risk AML and MDS: Interim results of a phase 2 trial. Blood 2003; 102(suppl. 1): 176a.
87. Kurzrock R, Kantarjian HM, Cottes JE, Singhania N, Thomas DA, Wilson EF, et al. Farnesyltransferase inhibitor R115777 in myelodysplastic syndrome: clinical and biologic activities in the phase 1 setting. Blood 2003; 102: 4527-34.
88. Kurzrock R, Albitar M, Cortes JE, Estey EH, Faderl SH, Garcia-Manero G, et al. Phase II study of R115777, a farnesyl transferase inhibitor, in myelodysplastic syndrome. J Clin Oncol 2004; 22: 1287-92.
89. Cortes J, Holyoake TL, Silver RT, Simonsson B, DeAngelo D, Turner AR, et al. Continuous oral lonafarnib (Sarasar™) for the treatment of patients with advanced hematologic malignancies: a phase II study. Blood 2002; 100(suppl. 1): 793a.
90. Feldman EJ, Cortes J, Holyoake TL, Simonsson B, DeAngelo DJ, Lipton JH, et al. Continuous oral lonafarnib (Sarasar™) for the treatment of patients with myelodysplastic syndrome. Blood 2003; 102(suppl. 1): 421a.
91. Lerner EC, Zhang TT, Knowles DB, Qian Y, Hamilton AD, Sebti SM. Inhibition of the prenylation of K-Ras, but not H- or N-Ras, is highly-resistant to CAAX peptidomimetics and requires both a farnesyltranferase and a geranylgeranyltransferase I inhibitor in human tumor cell lines. Oncogene 1997; 15: 1283-8.
92. 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: 5310-4.
93. Mangues R, Corral T, Kohl NE, Symmans WF, Lu S, Malumbres M, et al. Antitumor effect of a farnesyl protein transferase inhibitor in mammary and lymphoid tumors overexpressing N-Ras in transgenic mice. Cancer Res 1998; 58: 1253-9.
94. Omer CA, Chen Z, Diehl RE, Conner MW, Chen HY, Trumbauer ME, et al. Mouse mammary tumor virus-KiRasB transgenic mice develop mammary carcinomasthat can be growth-inhibited by a farnesyl protein transferase inhibitor. Cancer Res 2000; 60: 2680-8.
95. Zhang FL, Kirschmeier P, Carr D, James L, Bond RW, Wang L, et al. Characterization of HaRas, N-Ras, KiRas4A, and KiRas4B as in vitro substrates for farnesyl protein transferase and geranylgeranyl protein transferase type I. J Biol Chem 1997; 272: 10232-9.
96. Whyte DB, Kirschmeier 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: 14459-64.
97. Sun J, Qian Y, Hamilton AD, Sebti SM. Both farnesyltransferase and geranylgeranyltransferase I inhibitors are required for inhibition of oncogenic K-Ras prenylation but each alone is sufficient to suppress human tumor growth in nude mouse xenografts. Oncogene 1998; 16: 1467-73.
98. Prendergast GC, Davide JP, Lebowitz PF, Wechsler-Reya R, Kohl NE. Resistance of a variant Ras-transformed cell line to phenotypic reversion by farnesyl transferase inhibitors. Cancer Res 1996; 56: 2626-32.
99. Del Villar K, Urano J, Guo L, Tamanoi F. A mutant form of human protein farnesyltransferase exhibits increased resistance to farnesyltransferase inhibitors. J Biol Chem 1999; 274: 27010-7.
100. Smith V, Rowlands MG, Barrie E, Workman P, Kelland LR. Establishment and characterization of acquired resistance to the farnesyl protein transferase inhibitor R115777 in a human colon cancer cell line. Clin Cancer Res 2002; 8: 2002-9.
101. Hu W, Wu W, Yeung SC, Freedman RS, Kavanagh JJ, Verschraegen CF. Increased expression of hear shock protein 70 in adherent ovarian cancer and mesothelioma following treatment with manumycin, a farnesyl transferase inhibitor. Anticancer Res 2002; 22: 665-72.
102. Ptevost GP, Pradines A, Btezak MC, Lonchampt MO, Viossat I, Adet I, et al. Inhibition of human tumor cell growth in vivo by an orally bioavailable inhibitor of human farnesyl-transferase, BIM-46228. Int J Cancer 2001; 91: 718-22.
103. Moasser MM, Sepp-Lorenzino L, Kohl NE, Oliff A, Balog A, Su DS, et al. Farnesyl transferase inhibitors cause enhanced mitotic sensitivity to taxol and epothilones. Proc Natl Acad Sci USA 1998; 95: 1369-74.
104. Adjei AA, Davis JN, Bruzek LM, Erlichman C, Kaufmann SH. Synergy of the protein farnesyltransferase inhibitor SCH66336 and cisplatin in human cancer cell lines. Clin Cancer Res 2001; 7: 1438-45.
105. Shi B, Yaremko B, Hajian G, Terracina G, Bishop WR, Liu M, et al. The farnesyl protein transferase inhibitor SCH66336 synergizes with taxanes in vitro and enhances their antitumoral activity in vivo. Cancer Chemother Pharmacol 2000; 46: 387-93.
106. Smalley KS, Eisen TG. Farnesyl transferase inhibitor SCH66336 is cytostatic, pro-apoptotic and enhances chemosensibility to cisplatin in melanoma cells. Int J Cancer 2003; 105: 165-75.
107. Marley SB, Lewis JL, Schneider H, Rudd CE, Gordon MY. Phosphatidylinositol-3 kinase inhibitors reproduce the selective antiproliferative effects of imatinib on chronic myeloid leukaemia progenitor cells. Br J Haematol 2004; 125: 500-11.
108. Hoover RR, Mahon FX, Melo JV, Daley GQ. Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336. Blood 2003; 101: 2070-1.
109. Daley GQ. Towards combination target-directed chemotherapy for chronic myeloid leukemia: role of farnesyl transferase inhibitors. Semin Hematol 2005; 40(suppl 2): 11-4.
110. Cox AD, Toussaint LG III, Fiordalisi JJ, Rogers-Graham K, Der CJ. Farnesyltransferase and geranylgeranyltransferase inhibitors - The saga continues. In: Sebti SM, Hamilton AD, eds. Farnesyltransferase inhibitors in cancer therapy. Totowa, NJ: Humana Press, 2001: 255-73.
111. Patnaik A, Rowinsky EK. Early clinical experience with farnesyl protein transferase inhibitors: from the bench to the bedside. In: Sebti SM, Hamilton AD, eds. Farnesyltransferase inhibitors in cancer therapy. Totowa, NJ: Humana Press, 2001: 223-49.