Molecular targets in acute myelogenous leukemia

Blood Reviews

Volumn 17, Issue 1, 2003, Pages 15-23

  Stirewalt, Derek L ^a,c   Meshinchi, Soheil ^a,b   Radich, Jerald P ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^c Fred Hutchinson Cancer Research Center   (United States)

Author keywords

Acute myeloid leukemia; AML; FLT3; FMS; KIT; RAS; Treatment; Tyrosine kinase

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 2,4 DIMETHYL 5 (2 OXO 1H INDOL 3 YLMETHYLENE) 3 PYRROLEPROPIONIC ACID; 4 [6 METHOXY 7 [3 (1 PIPERIDINYL)PROPOXY] 4 QUINAZOLINYL] 1 PIPERAZINECARBOXYLIC ACID (4 ISOPROPOXYPHENYL)AMIDE; 5,6,7,13 TETRAHYDRO 12 (3 HYDROXYPROPYL) 9 ISOPROPOXYMETHYLINDENO[2,1 A]PYRROLO[3,4 C]CARBAZOL 5(12H) ONE; 6,7 DIMETHOXY 2 PHENYLQUINOXALINE; 6,7 DIMETHYL 2 PHENYLQUINOXALINE; BCR ABL PROTEIN; CEP 701; CISPLATIN; FLT3 LIGAND; FLT3 LIGAND INHIBITOR; GEMCITABINE; GENE PRODUCT; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HERBIMYCIN A; IMATINIB; LONAFARNIB; MIDOSTAURIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; PROTEIN FARNESYLTRANSFERASE INHIBITOR; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; RAS PROTEIN; SEMAXANIB; STAUROSPORINE DERIVATIVE; TIPIFARNIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN;

ACUTE GRANULOCYTIC LEUKEMIA; ARTICLE; ATAXIA; BONE MARROW SUPPRESSION; CANCER CHEMOTHERAPY; CLINICAL PATHWAY; CLINICAL TRIAL; CONFUSION; DRUG MECHANISM; DRUG TARGETING; DYSARTHRIA; ENZYME ACTIVATION; FATIGUE; GASTROINTESTINAL TOXICITY; GENE MUTATION; GENE TARGETING; HUMAN; MOLECULAR INTERACTION; NEUROTOXICITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; THROMBOEMBOLISM;

EID: 0037365086     PISSN: 0268960X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0268-960X(02)00057-7     Document Type: Article

References (116)

1. ARF links the tumour suppressor p53 to RAS. Nature 1998; 395: 125-126.
2. Hayakawa F, Towatari M, Kiyoi 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.
3. Mizuki M, Fenski R, Halfter H 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.
4. Delgado MD, Vaque JP, Arozarena I et al. H-, K- and N-Ras inhibit myeloid leukemia cell proliferation by a p21WAF1-dependent mechanism. Oncogene 2000; 19: 783-790.
5. Kelly LM, Yu J, Boulton CL et al. CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Caner Cell 2002.
6. Boettner B, Van Aelst L. The role of Rho GTPases in disease development. Gene 2002; 286: 155-174.
7. Byrne JL, Marshall CJ. The molecular pathophysiology of myeloid leukaemias: Ras revisited. Br J Haematol 1998; 100: 256-264.
8. Boguski MS, McCormick F. Proteins regulating Ras and its relatives. Nature 1993; 366: 643-654.
9. Gilliland DG, Griffin JD. Role of FLT3 in leukemia. Curr Opin Hematol 2002; 9: 274-281.
10. Bos JL. Ras oncogenes in human cancer: a review. Cancer Res 1989; 49:4682-4689.
11. Aaronson SA. Growth factors and cancer. Science 1991; 254: 1146-1153.
12. Agnes F, Shamoon B, Dina C et al. Genomic structure of the downstream part of the human FLT3 gene: exon/intron structure conservation among genes encoding receptor tyrosine kinases (RTK) of subclass III. Gene 1994; 145: 283-288.
13. Broudy VC. Stem cell factor and hematopoiesis. Blood 1997; 90: 1345-1364.
14. Rosnet O, Marchetto S, deLapeyriere O et al. Murine Flt3, a gene encoding a novel tyrosine kinase receptor of the PDGFR/CSFIR family. Oncogene 1991; 6: 1641-1650.
15. Small D, Levenstein M, Kim E et al. STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells. Proc Natl Acad Sci USA 1994; 91: 459-463.
16. Gelb MH. Protein prenylation, et cetera: signal transduction in two dimensions. Science 1997; 275: 1750-1751.
17. Koblan KS, Kohl NE, Omer CA et al. Farnesyltransferase inhibitors: a new class of cancer chemotherapeutics. Biochem Soc Trans 1996; 24: 688-692.
18. Zhang S, Mantel C, Broxmeyer HE. Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and their association with Grb2 and Shc in Baf3/Flt3 cells. J Leukoc Biol 1999; 65: 372-380.
19. Lennartsson J, Blume-Jensen P, Hermanson M et al. Phosphorylation of Shc by Src family kinases is necessary for stem cell factor receptor/c-kit mediated activation of the Ras/MAP kinase pathway and c-fos induction. Oncogene 1999; 18: 5546-5553.
20. Kang CD, Do IR, Kim KW et al. Role of Ras/ERK-dependent pathway in the erythroid differentiation of K562 cells. Exp Mol Med 1999; 31: 76-82.
21. Katz ME, McCormick F. Signal transduction from multiple Ras effectors. Curr Opin Genet Dev 1997; 7: 75-79.
22. Kauffmann-Zeh A, Rodriguez-Viciana P, Ulrich E et al. Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB. Nature 1997; 385: 544-548.
23. Khosravi-Far R, White MA et al. Oncogenic Ras activation of Raf/ mitogen-activated protein kinase-independent pathways is sufficient to cause tumorigenic transformation. Mol Cell Biol 1996; 16: 3923-3933.
24. Kishida S, Koyama S, Matsubara K et al. Colocalization of Ras and Ral on the membrane is required for Ras-dependent Ral activation through Ral GDP dissociation stimulator. Oncogene 1997; 15: 2899-2907.
25. Clark GJ, Westwick JK, Der CJ. p120 GAP modulates Ras activation of Jun kinases and transformation. J Biol Chem 1997; 272: 1677-1681.
26. Moodie SA, Willumsen BM, Weber MJ et al. Complexes of Ras. GTP with Raf-1 and mitogen-activated protein kinase kinase. Science 1993; 260: 1658-1661.
27. Lange-Carter CA, Pleiman CM, Gardner AM et al. A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf. Science 1993; 260: 315-319.
28. Zhao Y, Bjorbaek C, Moller DE. Regulation and interaction of pp90(rsk) isoforms with mitogen-activated protein kinases. J Biol Chem 1996; 271: 29773-29779.
29. Willard FS, Crouch MF. MEK, ERK, and p90RSK are present on mitotic tubulin in Swiss 3T3 cells: a role for the MAP kinase pathway in regulating mitotic exit. Cell Signal 2001; 13: 653-664.
30. Olson MF, Ashworth A, Hall A. An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through GI. Science 1995; 269: 1270-1272.
31. Ihie JN. Signaling by the cytokine receptor superfamily in normal and transformed hematopoietic cells. Adv Cancer Res 1996; 68: 23-65.
32. Taniguchi T. Cytokine signaling through nonreceptor protein tyrosine kinases. Science 1995; 268: 251-255.
33. Rane SG, Reddy EP. JAKs, STATs and Src kinases in hematopoiesis. Oncogene 2002; 21: 3334-3358.
34. Ridge SA, Worwood M, Oscier D et al. FMS mutations in myelodysplastic, leukemic, and normal subjects. Proc Natl Acad Sci USA 1990; 87: 1377-1380.
35. Tobal K, Pagliuca A, Bhatt B et al. Mutation of the human FMS gene (M-CSF receptor) in myelodysplastic syndromes and acute myeloid leukemia. Leukemia 1990; 4: 486-489.
36. Padua RA, Guinn BA, Al-Sabah AI et al. RAS, FMS and p53 mutations and poor clinical outcome in myelodysplasias: a 10-year follow-up. Leukemia 1998; 12: 887-892.
37. Gari M, Goodeve A, Wilson G et al. c-kit proto-oncogene exon 8 in-frame deletion plus insertion mutations in acute myeloid leukaemia. Br J Haematol 1999; 105: 894-900.
38. Sperr WR, Walchshofer S, Horny HP et al. Systemic mastocytosis associated with acute myeloid leukaemia: report of two cases and detection of the c-kit mutation Asp-816 to Val. Br J Haematol 1998; 103: 740-749.
39. Nakao M, Yokota S, Iwai T et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia 1996; 10: 1911-1918.
40. Kiyoi H, Towatari M, Yokota S et al. Internal tandem duplication of the FLT3 gene is a novel modality of elongation mutation which causes constitutive activation of the product. Leukemia 1998; 12: 1333-1337.
41. Kiyoi H, Naoe T, Yokota S et al. Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia. Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho). Leukemia 1997; 11: 1447-1452.
42. Xu F, Taki T, Yang HW et al. Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children. Br J Haematol 1999; 105: 155-162.
43. Yokota S, Kiyoi H, Nakao M et al. Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines. Leukemia 1997; 11: 1605-1609.
44. Stirewalt DL, Kopecky KJ, Meshinchi S et al. FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood 2001; 97: 3589-3595.
45. Meshinchi S, Woods WG, Stirewalt DL et al. Prevalence and prognostic significance of FLT3 internal tandem duplication in pediatric acute myeloid leukemia. Blood 2001; 97: 89-94.
46. Iwai T, Yokota S, Nakao M et al. Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Children's Cancer and Leukemia Study Group, Japan. Leukemia 1999; 13: 38-43.
47. Schnittger S, Schoch C, Dugas M et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood 2002; 100: 59-66.
48. Thiede C, Steudel C, Mohr B 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.
49. Abu-Duhier FM, Goodeve AC, Wilson GA et al. FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group. Br J Haematol 2000; 111: 190-195.
50. Lyman SD. Biology of flt3 ligand and receptor. Int J Hematol 1995; 62: 63-73.
51. Lisovsky M, Estrov Z, Zhang X et al. Flt3 ligand stimulates proliferation and inhibits apoptosis of acute myeloid leukemia cells: regulation of Bcl-2 and Bax. Blood 1996; 88: 3987-3997.
52. Yamamoto Y, Kiyoi H, Nakano Y et al. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood 2001; 97: 2434-2439.
53. Abu-Duhier FM, Goodeve AC, Wilson GA et al. Identification of novel FLT-3 Asp835 mutations in adult acute myeloid leukaemia. Br J Haematol 2001; 113: 983-988.
54. Kelly LM, Liu Q, Kutok JL et al. FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model. Blood 2002; 99: 310-318.
55. Kelly LM, Kutok JL, Williams IR et al. PML/PARα and FLT3-ITD induce an APL-like disease in a mouse model. Proc Natl Acad Sci USA 2002; 99: 8283-8288.
56. Farr CJ, Saiki RK, Erlich HA et al. Analysis of RAS gene mutations in acute myeloid leukemia by polymerase chain reaction and oligonucleotide probes. Proc Natl Acad Sci USA 1988; 85: 1629-1633.
57. Bartram CR, Ludwig WD, Hiddemann W et al. Acute myeloid leukemia: analysis of ras gene mutations and clonality defined by polymorphic X-linked loci. Leukemia 1989; 3: 247-256.
58. Radich JP, Kopecky KJ, Willman CL et al. N-ras mutations in adult de novo acute myelogenous leukemia: prevalence and clinical significance. Blood 1990; 76: 801-807.
59. Bos JL, Verlaan-de Vries M, van der Eb AJ et al. Mutations in N-ras predominate in acute myeloid leukemia. Blood 1987; 69: 1237-1241.
60. Vogelstein B, Civin CI, Preisinger AC et al. RAS gene mutations in childhood acute myeloid leukemia: a Pediatric Oncology Group study. Genes Chromosomes Cancer 1990; 2: 159-162.
61. Neubauer A, Dodge RK, George SL et al. Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia. Blood 1994; 83: 1603-1611.
62. Paquette RL, Landaw EM, Pierre RV et al. N-ras mutations are associated with poor prognosis and increased risk of leukemia in Myelodysplasia Syndrome. Blood 1993; 82: 590-599.
63. Miyauchi J, Asada M, Sasaki M et al. Mutations of the N-ras gene in juvenile chronic myelogenous leukemia. Blood 1994; 83: 2248-2254.
64. Flotho C, Valcamonica S, Mach-Pascual S et al. RAS mutations and clonality analysis in children with juvenile myelomonocytic leukemia (JMML). Leukemia 1999; 13: 32-37.
65. Hirsch-Ginsberg C, LeMaistre AC, Kantarjian H et al. RAS mutations are rare events in Philadelphia chromosome-negative/bcr gene rearrangement-negative chronic myelogenous leukemia, but are prevalent in chronic myelomonocytic leukemia. Blood 1990; 76: 1214-1219.
66. Collins SJ, Howard M, Andrews DF et al. Rare occurrence of N-ras point mutations in Philadelphia chromosome positive chronic myeloid leukemia. Blood 1989; 73: 1028-1032.
67. Towatari M, lida H, Tanimoto M et al. Constitutive activation of mitogen-activated protein kinase pathway in acute leukemia cells. Leukemia 1997; 11: 479-484.
68. Lida M, Towatari M, Nakao A et al. Lack of constitutive activation of MAP kinase pathway in human acute myeloid leukemia cells with N-Ras mutation. Leukemia 1999; 13: 585-589.
69. Morgan MA, Dolp O, Reuter CW. 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: 1823-1834.
70. Serrano M, Lin AW, McCurrach ME et al. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 1997; 88: 593-602.
71. Birkenkamp KU, Geugien M, Lemmink HH et al. Regulation of constitutive STAT5 phosphorylation in acute myeloid leukemia blasts. Leukemia 2001; 15: 1923-1931.
72. Schuringa JJ, Wierenga AT, Kruijer W et al. Constitutive Stat3, Tyr705, and Ser727 phosphorylation in acute myeloid leukemia cells caused by the autocrine secretion of interleukin-6. Blood 2000; 95: 3765-3770.
73. Ning ZQ, Li J, Arceci RJ. Signal transducer and activator of transcription 3 activation is required for Asp(816) mutant c-Kit-mediated cytokine-independent survival and proliferation in human leukemia cells. Blood 2001; 97: 3559-3567.
74. Peeters P, Raynaud SD, Cools J et al. Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9; 12) in a lymphoid and t(9; 15; 12) in a myeloid leukemia. Blood 1997; 90: 2535-2540.
75. Lacronique V, Boureux A, Valle VD et al. A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Science 1997; 278: 1309-1312.
76. Pendergast AM, Quilliam LA, Cripe LD et al. BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell 1993; 75: 175-185.
77. Golub TR, Barker GF, Lovett M et al. Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5; 12) chromosomal translocation. Cell 1994; 77: 307-316.
78. Fenski R, Flesch K, Serve S et al. Constitutive activation of FLT3 in acute myeloid leukaemia and its consequences for growth of 32D cells. Br J Haematol 2000; 108: 322-330.
79. Druker BJ, Lydon NB. Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Invest 2000; 105: 3-7.
80. Carroll M, Ohno-Jones S, Tamura S et al. CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood 1997; 90: 4947-4952.
81. Druker BJ, Sawyers CL, Kantarjian H 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.
82. Heinrich MC, Griffith DJ, Druker BJ et al. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 2000; 96: 925-932.
83. Beghini A, Cairoli R, Morra E et al. In vivo differentiation of mast cells from acute myeloid leukemia blasts carrying a novel activating ligand-independent C-kit mutation. Blood Cells Mol Dis 1998; 24: 262-270.
84. Ma Y, Zeng S, Metcalfe DD et al. The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations. Blood 2002; 99: 1741-1744.
85. Smolich BD, Yuen HA, West KA et al. The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts. Blood 2001; 97: 1413-1421.
86. Mesters RM, Padro T, Bieker R et al. Stable remission after administration of the receptor tyrosine kinase inhibitor SU5416 in a patient with refractory acute myeloid leukemia. Blood 2001; 98: 241-243.
87. Kuenen BC, Rosen L, Smit EF et al. Dose-finding and pharmacokinetic study of cisplatin, gemcitabine, and SU5416 in patients with solid tumors. J Clin Oncol 2002; 20: 1657-1667.
88. Mackarehtschian K, Hardin JD, Moore KA et al. Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive hematopoietic progenitors. Immunity 1995; 3: 147-161.
89. Zhao M, Kiyoi H, Yamamoto Y et al. In vivo treatment of mutant FLT3-transformed murine leukemia with a tyrosine kinase inhibitor. Leukemia 2000; 14: 374-378.
90. Tse KF, Novelli E, Civin CI et al. Inhibition of FLT3-mediated transformation by use of a tyrosine kinase inhibitor. Leukemia 2001; 15: 1001-1010.
91. Levis M, Tse KF, Smith BD et al. A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT3 internal tandem duplication mutations. Blood 2001; 98: 885-887.
92. Allebach J, Levis M, Fai-Tse K et al. FLT3-targeted tyrosine kinase inhibitors inhibit proliferation, induce apoptosis, and improve survival in a murine leukemia model utilizing FLT3/ITD-transformed cells. Blood 2001; 89: 118a.
93. Levis M, Allebach J, Tse KF et al. A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo. Blood 2002; 99: 3885-3891.
94. Levis M, Allebach J, Fai-Tse K et al. FLT3-targeted inhibitors kill FLT3-dependent modeled cells, leukemia-derived cell lines, and primary AML blasts in vitro and in vivo. Blood 2001; 89: 721a.
95. Yee KWH, O'Farrell A, Smolich BD et al. SU5416 and SU5614 inhibit wild-type and activated mutant FLT3 signaling in leukemia cells. Blood 2001; 89.
96. O'Farrell A, Abrams T, Yuen H et al. Sugen compounds SU5416 and SU11248 inhibit Flt3 activity: therapeutic application in AML. Blood 2001; 89: 118a.
97. Weisberg E, Boulton C, Kelly LM et al. Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell 2002; 1: 433-443.
98. Lerner EC, Qian Y, Blaskovich MA et al. Ras CAAX peptidomimetic FTI-277 selectively blocks oncogenic Ras signaling by inducing cytoplasmic accumulation of inactive Ras-Raf complexes. J Biol Chem 1995; 270: 26802-26806.
99. Cox AD, Garcia AM, Westwick JK et al. The CAAX peptidomimetic compound B581 specifically blocks farnesylated, but not geranylgeranylated or myristylated, oncogenic ras signaling and transformation. J Biol Chem 1994; 269: 19203-19206.
100. Miquel K, Pradines A, Sun J et al. GGTI-298 induces G0-G1 block and apoptosis whereas FTI-277 causes G2-M enrichment in A549 cells. Cancer Res 1997; 57: 1846-1850.
101. Sepp-Lorenzino L, Rosen N. A farnesyl-protein transferase inhibitor induces p21 expression and G1 block in p53 wild type tumor cells. J Biol Chem 1998; 273: 20243-20251.
102. Sun J, Qian Y, Hamilton AD et al. Ras CAAX peptidomimetic FTI 276 selectively blocks tumor growth in nude mice of a human lung carcinoma with K-Ras mutation and p53 deletion. Cancer Res 1995; 55: 4243-4247.
103. Sun J, Qian Y, Hamilton AD et al. 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: 1467-1473.
104. Sepp-Lorenzino L, Ma Z, Rands E 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: 5302-5309.
105. Prendergast GC, Davide JP, deSolms SJ 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.
106. Oliff A. Farnesyltransferase inhibitors: targeting the molecular basis of cancer. Biochim Biophys Acta 1999; 1423: C19-C30.
107. Lebowitz PF, Prendergast GC. Non-Ras targets of farnesyltransferase inhibitors: focus on Rho. Oncogene 1998; 17: 1439-1445.
108. Liu A, Du W, Liu JP et al. RhoB alteration is necessary for apoptotic and antineoplastic responses to farnesyltransferase inhibitors. Mol Cell Biol 2000; 20: 6105-6113.
109. Adjei AA, Erlichman C et al. A Phase I trial of the farnesyl transferase inhibitor SCH66336: evidence for biological and clinical activity. Cancer Res 2000; 60: 1871-1877.
110. Hoover RR, Mahon FX, Melo JV et al. Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336. Blood 2002; 100: 1068-1071.
111. Peters DG, Hoover RR, Gerlach MJ et al. Activity of the farnesyl protein transferase inhibitor SCH66336 against BCR/ABL-induced murine leukemia and primary cells from patients with chronic myeloid leukemia. Blood 2001; 97: 1404-1412.
112. Crul M, de Klerk GJ, Swart M et al. Phase I clinical and pharmacologic study of chronic oral administration of the farnesyl protein transferase inhibitor R115777 in advanced cancer. J Clin Oncol 2002; 20: 2726-2735.
113. Karp JE, Lancet JE, Kaufmann SH et al. Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase I clinical-laboratory correlative trial. Blood 2001; 97: 3361-3369.
114. Fukazawa H, Uehara Y. U0126 reverses Ki-ras-mediated transformation by blocking both mitogen-activated protein kinase and p70 S6 kinase pathways. Cancer Res 2000; 60: 2104-2107.
115. Frank DA. STAT signaling in the pathogenesis and treatment of cancer. Mol Med 1999; 5: 432-456. Available from: ny.com/link/ service/journals/00020/bibs/5n7p432.html.
116. Marra F, Choudhury GG, Abboud HE. Interferon-y-mediated activation of STAT1α regulates growth factor-induced mitogenesis. J Clin Invest 1996; 98: 1218-1230.