Farnesyl transferase inhibitors

Cancer Investigation

Volumn 26, Issue 7, 2008, Pages 653-661

  Li, Tianhong ^a   Sparano, Joseph A ^a  

^a ALBERT EINSTEIN CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANASTROZOLE; ANTHRACYCLINE; AROMATASE INHIBITOR; CAPECITABINE; CARBOPLATIN; CYCLOPHOSPHAMIDE; CYTOTOXIC AGENT; DOXORUBICIN; FULVESTRANT; GEMCITABINE; GUANINE NUCLEOTIDE BINDING PROTEIN; LETROZOLE; LONAFARNIB; PACLITAXEL; PROTEIN FARNESYLTRANSFERASE INHIBITOR; RAS PROTEIN; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; TAMOXIFEN; TIPIFARNIB; TRASTUZUMAB;

ANEMIA; AREA UNDER THE CURVE; BREAST CANCER; BREAST CARCINOMA; CLINICAL TRIAL; DIARRHEA; DIGESTIVE SYSTEM CANCER; DRUG ACTIVITY; DRUG EFFECT; DRUG POTENTIATION; FATIGUE; HORMONAL THERAPY; HUMAN; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUROTOXICITY; NEUTROPENIA; ONCOGENE RAS; PRIORITY JOURNAL; PROTEIN PROCESSING; RASH; REVIEW; THROMBOCYTOPENIA; VOMITING;

ANIMALS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC AGENTS, HORMONAL; BREAST NEOPLASMS; CELL SURVIVAL; DRUG DESIGN; DRUG RESISTANCE, NEOPLASM; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME INHIBITORS; FARNESYLTRANSTRANSFERASE; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MODELS, ANIMAL; MUTATION; NEOPLASMS; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTO-ONCOGENE PROTEINS P21(RAS); SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

EID: 48249129674     PISSN: 07357907     EISSN: 15324192     Source Type: Journal    
DOI: 10.1080/07357900801971016     Document Type: Review

References (97)

1. Burgoyne, R.D. Small GTP-binding proteins. Trends Biochem Sci 1989, 14 (10), 394-396.
2. Chardin, P. Small GTP-binding proteins of the ras family: a conserved functional mechanism? Cancer Cells 1991, 3 (4), 117-126.
3. Downward, J. The ras superfamily of small GTP-binding proteins. Trends Biochem Sci 1990, 15 (12), 469-472.
4. Hall, A. The cellular functions of small GTP-binding proteins. Science 1990, 249 (4969), 635-640.
5. Takai, Y.; Sasaki, T.; Matozaki, T. SmaUGTP-bindingproteins. Physiol Rev 2001, 81 (l), 153-208.
6. Takai, Y.; Kikuchi, A.; Kawata, M.; Yamamoto, K.; Hoshijima, M. Purification, characterization, and possible functions of small molecular weight GTP-binding proteins. Am J Hypertens 1990, 3 (8 Pt 2), 220S-223S.
7. Basso, A.D.; Kirschmeier, P.; Bishop, W.R. Thematic review series: lipid posttranslational modifications. Farnesyl transferase inhibitors. J Lipid Res 2006, 47 (1), 15-31.
8. Sebti, S.M; Hamilton, A.D. Inhibition of Ras prenylation: a novel approach to cancer che motherapy. Pharmacol Ther 1997, 74 (1), 103-114.
9. Rowinsky, E.K.; Windle, J.J.; Von Hoff, D.D. Ras protein farnesyltransferase: a strategic target for anticancer therapeutic development. J Clin Oncol 1999, 17 (11), 3631-3652.
10. Sebti, S.M; Hamilton, A.D. Farnesyltransferase and geranylgeranyltransferase I inhibitors and cancer therapy: lessons from mechanism and bench-to-bedside translational studies. Oncogene 2000, 19 (56), 6584-6593.
11. Thoma, N.H; lakovenko, A.; Owen, D.; et al. Phosphoisoprenoid binding specificity of geranylgeranyltransferase type II. Biochemistry 2000, 39 (39), 12043-12052.
12. Lobell, R.B.; Omer, C.A.; Abrams, M.T.; et al. Evaluation of farnesyhprotein transferase and geranylgeranyhprotein transferase inhibitor combinations in preclinical models. Cancer Res 2001, 61 (24), 8758-8768.
13. Cherfils, J.; Chardin, P. GEFs: structural basis for their activation of small GTP-binding proteins. Trends Biochem Sci 1999, 24 (8), 306-311.
14. Paduch, M.; Jelen, F.; Otlewski, J. Structure of small G proteins and their regulators. Acta Biochim Pol 2001, 48 (4), 829-850.
15. Feinberg, A.P.; Vogelstein, B.; Droller, M.J.; Baylin, S.B.; Nelkin, B.D. Mutation affecting the 12th amino acid of the c-Ha-ras oncogene product occurs infrequently in human cancer. Science 1983, 220 (4602), 1175-1177.
16. Fearon, E.R. K-ras gene mutation as a pathogenetic and diagnostic marker in human cancer. J Natl Cancer Inst 1993, 85 (24), 1978-1980.
17. Thor, A.; Ohuchi, N.; Hand, PH.; et al. Ras gene alterations and enhanced levels of ras p21 expression in a spectrum of benign and malignant human mammary tissues. Lab Invest 1986, 55 (6), 603-615.
18. Rochlitz, C.F.; Scott, G.K.; Dodson, J.M.; et al. Incidence of activating ras oncogene mutations associated with primary and metastatic human breast cancer. Cancer Res 1989, 49 (2), 357-360.
19. Clark, G.J.; Der, C.J. Aberrant function of the Ras signal transduction pathway in human breast cancer. Breast Cancer Res Treat 1995, 35 (1), 133-144.
20. Malaney, S.; Daly, R.J. The ras signaling pathway in mammary tumorigenesis and meta stasis. J Mammary Gland Biol Neoplasia 2001, 6 (1), 101-113.
21. Kato, S.; Masuhiro, Y.; Watanabe, M.; et al. Molecular mechanism of a cross-talk between oestrogen and growth factor signalling pathways. Genes Cells 2000, 5 (8), 593-601.
22. Smith, C.A.; Pollice, A.A.; Gu, L.P.; et al. Correlations among p53, Her-2/neu, and ras over-expression and aneuploidy by multiparameter flow cytometry in human breast cancer: evidence for a common phenotypic evolutionary pattern in infiltrating ductal carcinomas. Clin Cancer Res 2000, 6 (1), 112-126.
23. Bunone, G.; Briand, P.A.; Miksicek, R.J.; Picard, D. Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. Embo J 1996, 15 (9), 2174-2183.
24. Ikehara, N.; Semba, S.; Sakashita, M.; Aoyama, N.; Kasuga, M.; Yokozaki, H. BRAF mutation associated with dysregulation of apoptosis in human colorectal neoplasms. Int J Cancer 2005, 115 (6), 943-950.
25. Kleer, C.G.; Griffith, K.A.; Sabel, M.S.; et al. RhoC-GTPase is a novel tissue biomarker associ ated with biologically aggressive carcinomas of the breast. Breast Cancer Res Treat 2005, 93 (2), 101-110.
26. Kleer, C.G.; van Golen, K.L.; Zhang, Y.; Wu, Z.F.; Rubin, M.A.; Merajver, S.D. Characterization of RhoC expression in benign and malignant breast disease: a potential new marker for small breast carcinomas with metastatic ability. Am J Pathol 2002, 160 (2), 579-584.
27. Kleer, C.G.; Zhang, Y.; Pan, Q.; et al. WISPS and RhoC guanosine triphosphatase cooperate in the development of inflammatory breast cancer. Breast Cancer Res 2004, 6 (2), R110-R115.
28. van Golen, K.L.; Davies, S.; Wu, Z.F.; et al. A novel putative low-affinity insulin-like growth factor-binding protein, LIBC (lost in inflammatory breast cancer), and RhoC GTPase correlate with the inflammatory breast cancer phenotype. Clin Cancer Res 1999, 5 (9), 2511-2519.
29. Gibbs, J.B.; Oliff, A.; Kohl, N.E. Farnesyltransferase inhibitors: Ras research yields a potential cancer therapeutic. Cell 1994, 77 (2), 175-178.
30. Marshall, C.J. Cell signalling. Raf gets it together. Nature 1996, 383 (6596), 127-128.
31. Adjei, A.A. Blocking oncogenic Ras signaling for cancer therapy. J Natl Cancer Inst 2001, 93 (14), 1062-1074.
32. Li, T.; Sparano, J.A. Inhibiting Ras signaling in the therapy of breast cancer. Clin Breast Cancer 2003, 3 (6), 405-416; discussion 17-20.
33. Wright, J.J.; Zerivitz, K.; Gravell, A.E.; Cheson, B.D. Clinical trials referral resource. Current clinical trials of R115777 (Zarnestra). Oncology (Huntingt) 2002, 16 (7), 930-931.
34. Venet, M.; End, D.; Angibaud, P. Farnesyl protein transferase inhibitor ZARNESTRA R115777-history of a discovery. Curr Top Med Chem 2003, 3 (10), 1095-1102.
35. Johnston, S.R. Farnesyl transferase inhibitors: a novel targeted therapy for cancer. Lancet Oncol 2001, 2 (l), 18-26.
36. Caraglia, M.; Budillon, A.; Tagliaferri, P.; Marra, M.; Abbruzzese, A.; Caponigro, F. Isoprenylation of intracellular proteins as a new target for the therapy of human neo-plasma: preclinical and clinical implications. Curr Drug Targets 2005, 6 (3), 301-323.
37. Johnston, S.R.; Hickish, T.; Ellis, P.; et al. Phase II study of the efficacy and tolerability of two dosing regimens of the farnesyl transferase inhibitor, R115777, in advanced breast cancer. J Clin Oncol 2003, 21 (13), 2492-2499.
38. Johnston, S.; Semiglazov, V.; Manikhas, G.; et al. A randomised, blinded, phase II study of tipi-farnib (Zarnestra) combined with letrozole in the treatment of advanced breast cancer after antiestrogen therapy. San Antonio Breast Cancer Symposium 2005, (Abstr#5087).
39. Sparano, J.A.; Moulder, S.; Kazi, A.; et al. Targeted inhibition of farnesyltransferase in locally advanced breast cancer: a phase I and II trial of tipifarnib plus dose-dense doxorubicin and cyclophosphamide. J Clin Oncol 2006, 24, 3013-3018.
40. End, D.W.; Smets, G.; Todd, A.V.; et al. Characterization of the antitumor effects of the selec tive farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res 2001, 61 (1), 131-137.
41. Pan, J.; Yeung, S.C. Recent advances in understanding the antineoplastic mechanisms of farnesyltransferase inhibitors. Cancer Res 2005, 65 (20), 9109-9112.
42. Sepp-Lorenzino, L.; Rosen, N. A farnesyl-protein transferase inhibitor induces p21 expression and Gl block in p53 wild type tumor cells. J Biol Chem 1998, 273 (32), 20243-20251.
43. Ashar, H.R.; James, L.; Gray, K.; et al. The farnesyl transferase inhibitor SCH 66336 induces a G(2) → Mor G(1) pause in sensitive human tumor cell lines. Exp Cell Res 2001, 262 (l), 17-27.
44. Le Gouill, S.; Pellat-Deceunynck, C.; Harousseau, J.L.; et al. Farnesyl transferase inhibitor R115777 induces apoptosis of human myeloma cells. Leukemia 2002, 16 (9), 1664-1667.
45. Takada, Y.; Khuri, P.R.; Aggarwal, B.B. Protein farnesyltransferase inhibitor (SCH 66336) abolishes NF-kappaB activation induced by various carcinogens and inflammatory stimuli leading to suppression of NF-kappaB-regulated gene expression and up- regulation of apoptosis. J Biol Chem 2004, 279 (25), 26287-26299.
46. Xue, X.; Lai, K.T.; Huang, J.F.; Gu, Y.; Karlsson, L.; Fourie, A. Antiinflammatory activity in vitro and in vivo of the protein farnesyltransferase inhibitor tipifarnib. J Pharmacol Exp Ther 2006, 317, 53-60.
47. Pan, J.; She, M.; Xu, Z.X.; Sun, L.; Yeung, S.C. Farnesyltransferase inhibitors induce DNA damage via reactive oxygen species in human cancer cells. Cancer Res 2005, 65 (9), 3671-3681.
48. Han, J.Y.; Oh, S.H.; Morgillo, F.; et al. Hypoxia-inducible factor 1 alpha and antiangiogenic activity of farnesyltransferase inhibitor SCH66336 in human aerodigestive tract cancer. J Natl Cancer Inst 2005, 97 (17), 1272-1286.
49. Smith, V.; Rowlands, M.G.; Barrie, E.; Workman, P.; Kelland, L.R. Establishment and character ization of acquired resistance to the farnesyl protein transferase inhibitor R115777 in a human colon cancer cell line. Clin Cancer Res 2002, 8 (6), 2002-2009.
50. Sparreboom, A.; Marsh, S.; Mathijssen, R.H.; Verweij, J.; McLeod, H.L. Pharmacogenetics of tipifarnib (R115777) transport and metabolism in cancer patients. Invest New Drugs 2004, 22 (3), 285-289.
51. Bruzek, L.M.; Poynter, J.N.; Kaufmann, S.H.; Adjei, A.A. Characterization of a human carci noma cell line selected for resistance to the farnesyl transferase inhibitor 4-(2-(4-(8- chloro-3, 10-dibromo-6,ll-dihydro-5H-benzo-(5, 6)-cyclohepta(l,2-b)-pyridin-ll(R)-yl)-l-piperidinyl)-2-oxo-ethyl) -l-piperidinecarboxamide (SCH66336). Mol Pharmacol 2005, 68 (2), 477-486.
52. Nicholson, R.I.; Gee, J.M. Oestrogen and growth factor cross-talk and endocrine insensitivity and acquired resistance in breast cancer. Br J Cancer 2000, 82 (3), 501-513.
53. Katzenellenbogen, B.S.; Montano, M.M.; Ekena, K.; Herman, M.E.; Mclnerney, E.M.; William, L. McGuire Memorial Lecture. Antiestrogens: mechanisms of action and resistance in breast cancer. Breast Cancer Res Treat 1997, 44 (1), 23-38.
54. Kato, S.; Endoh, H.; Masuhiro, Y.; et al. Activation of the estrogen receptor through phos- phorylation by mitogen-activated protein kinase. Science 1995, 270 (5241), 1491-1494.
55. Cestac, P.; Sarrabayrouse, G.; Medale-Giamarchi, C.; et al. Prenylation inhibitors stimu late both estrogen receptor alpha transcriptional activity through AF-1 and AF-2 and estrogen receptor beta transcriptional activity. Breast Cancer Res 2005, 7 (1), R60-R70.
56. Dalenc, F.; Giamarchi, C.; Petit, M.; Poirot, M.; Favre, G.; Faye, J.C. Farnesyl-transferase inhibitor R115,777 enhances tamoxifen inhibition of MCF-7 cell growth through estrogen receptor dependent and independent pathways. Breast Cancer Res 2005, 7 (6), R1159-R1167.
57. Weinstein-Oppenheimer, C.R.; Henriquez-Roldan, C.F.; Davis, J.M.; et al. Role of the Raf signal transduction cascade in the in vitro resistance to the anticancer drug doxorubicin. Clin Cancer Res 2001, 7 (9), 2898-2907.
58. Cornwell, M.M.; Smith, D.E. A signal transduction pathway for activation of the rndrl promoter involves the proto-oncogene c-raf kinase. J Biol Chem 1993, 268 (21), 15347-15350.
59. Kim, S.H.; Lee, S.H.; Kwak, N.H.; Kang, C.D.; Chung, B.S. Effect of the activated Raf protein kinase on the humanmultidrug resistance 1 (MDR1) gene promoter. Cancer Lett 1996, 98 (2), 199-205.
60. Wang, E.; Casciano, C.N.; Clement, R.P.; Johnson, W.W. The farnesyl protein transferase inhibitor SCH66336 is a potent inhibitor of MDR1 product P-glycoprotein. Cancer Res 2001, 61 (20), 7525-7529.
61. Wang, E.J.; Johnson, W.W. The farnesyl protein transferase inhibitor lonafarnib (SCH66336) is an inhibitor of multidrug resistance proteins 1 and 2. Chemotherapy 2003, 49 (6), 303-308.
62. Rasouli-Nia, A.; Liu, D.; Perdue, S.; Britten, R.A. High Raf-1 kinase activity protects human tumor cells against paclitaxel-induced cytotoxicity. Clin Cancer Res 1998, 4 (5), 1111-1116.
63. Izbicka, E.; Campos, D.; Carrizales, G.; Patnaik, A. Biomarkers of anticancer activity of R115777 (Tipifarnib, Zarnestra) in human breast cancer models in vitro. Anticancer Res 2005 25 (5), 3215-3223.
64. Marcus, A.I.; Zhou, J.; O'Brate, A.; et al. The synergistic combination of the farnesyl transfer ase inhibitor lonafarnib and paclitaxel enhances tubulin acetylation and requires a func tional tubulin deacetylase. Cancer Res 2005, 65 (9), 3883-3893.
65. Zhu, K.; Gerbino, E.; Beaupre, D.M.; et al. Farnesyltransferase inhibitor R115777 (Zarnestra, Tipifarnib) synergizes with paclitaxel to induce apoptosis and mitotic arrest and to inhibit tumor growth of multiple myeloma cells. Blood 2005, 105 (12), 4759-4766.
66. Zimmerman, T.M.; Harlin, H.; Odenike, O.M.; et al. Dose-ranging pharmacodynamic study of tipifarnib (R115777) in patients with relapsed and refractory hematologic malignan cies. J Clin Oncol 2004, 22 (23), 4816-4822.
67. Cortes, J. Farnesyl transferase inhibitor R115777 in myelodysplastic syndrome. Curr Hematol Rep 2004, 3 (3), 157-158.
68. Cortes, J.; Albitar, M.; Thomas, D.; et al. Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies. Blood 2003, 101 (5), 1692-1697.
69. Gotlib, J. Farnesyltransferase inhibitor therapy in acute myelogenous leukemia. Curr Hematol Rep 2005, 4 (1), 77-84.
70. Rao, S.; Cunningham, D.; de Gramont, A.; et al. Phase III double-blind placebo-controlled study of farnesyl transferase inhibitor R115777 in patients with refractory advanced colorectal cancer. J Clin Oncol 2004, 22 (19), 3950-3957.
71. Lebowitz, P.F.; Eng-Wong, J.; Widemann, B.C.; et al. A phase I trial and pharmacokinetic study of tipifarnib, a farnesyltransferase inhibitor, and tamoxifen in metastatic breast cancer. Clin Cancer Res 2005, 11 (3), 1247-1252.
72. Goss, P.E.; Strasser, K. Aromatase inhibitors in the treatment and prevention of breast cancer. J Clin Oncol 2001, 19 (3), 881-894.
73. Ariazi, E.A.; Ariazi, J.L.; Cordera, F.; Jordan, V.C. Estrogen receptors as therapeutic targets in breast cancer. Curr Top Med Chem 2006, 6 (3), 195-216.
74. Carlson, R.W.; Brown, E.; Burstein, H.J.; et al. NCCN task force report: adjuvant therapy for breast cancer. J Natl Compr Cane Net 2006, 4 (suppl 1), S1-S26.
75. John, A. Glapsy. Phase II randomized study of Anastrazole with or without lonafarnib in postmenopausal women with hormone receptor-positive stage IIIB, IIIC or IV breast cancer. http://www.clinicaltrials.gov/ct/show/NCT00098904
76. Howell, A.; Robertson, J.F.; Quaresma Albano, J.; et al. Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer pro gressing after prior endocrine treatment. J Clin Oncol 2002, 20 (16), 3396-3403.
77. Osborne, C.K.; Pippen, J.; Jones, S.E.; et al. Double-blind, randomized trial comparing the effi cacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol 2002, 20 (16), 3386-3395.
78. Howell, A.; Robertson, J.F.; Abram, P.; et al. Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. J Clin Oncol 2004, 22 (9), 1605-1613.
79. Vahdat, L.T. Phase II study of tipifarnib and fulvestrant as second-line therapy in postmenopausal women with hormone receptor-positive inoperable locally advanced or metastatic breast cancer with progressive disease after prior first-line endocrine therapy. http://www.clinicaltrials.gov/ct/show/ NCT00082810
80. Fisher, B.; Brown, A.; Mamounas, E.; et al. Effect of preoperative chemotherapy on local- regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 1997, 15 (7), 2483-2493.
81. Bear, H.D.; Anderson, S.; Brown, A.; et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: prelimi nary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 2003, 21 (22), 4165-4174.
82. Guarneri, V.; Broglio, K.; Kau, S.W.; et al. Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol 2006, 24 (7), 1037-1044.
83. Citron, M.L.; Berry, D.A.; Cirrincione, C.; et al. Randomized trial of dose-dense versus con ventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 2003, 21 (8), 1431-1439.
84. William, J. Gradishar. Phase II study of capecitabine and tipifarnib in women with taxane-resistant metastatic breast cancer, http://www.clinicaltrials. gov/ct/show/ NCT00077363
85. Banu Arun. Phase I/II study of tipifarnib and gemcitabine in women with metastatic breast cancer. http://www.clinicaltrials.gov/ct/show/NCT00100750
86. Jan, H.M.; Schellens. Phase I study of lonafarnib, trastuzumab (herceptin®), and paclitaxel in patients with HER2/Neuoverexpressing stage IIIB, IIIC, or IV breast cancer, http://www.clinicaltrials.gov/ct/show/ NCT00068757
87. Van Cutsem, E.; van de Velde, H.; Karasek, P.; et al. Phase III trial of gemcitabine plus tipi farnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol 2004, 22 (8), 1430-1438.
88. Werner Meier. An open-label, multicenter, randomized phase II study to compare the effects of paclitaxel/carboplatin and lonafarnib to those of paclitaxel/carboplatin for first-line treatment of patients with epithelial ovarian cancer FIGO stages IIB-IV http://www.clinicaltrials.gov/ct/show/ NCT00281515
89. Schering-Plough. A pivotal randomized study of lonafarnib versus placebo in the treatment of subjects with myelodysplastic syndrome (MDS) or chronic myelomonocytic leu kemia (CMML) who are platelet transfusion dependent with or without anemia, http://www.clinicaltrials.gov/ct/show/NCT00109538
90. Adjei, A.; Croghan, G.A.; Erlichman, C.; et al. A phase I trial of the farnesyltransferase inhibi tor R115777, in combination with gemcitabine and cisplatin in patients with advanced cancer. Clin Cancer Res 2003, 9, 2520-2526.
91. Kelland, L.R.; Smith, V.; Valenti, M.; et al. Preclinical antitumor activity and pharmacodynamic studies with the farnesyl protein transferase inhibitor R115777 in human breast cancer. Clin Cancer Res 2001, 7 (11), 3544-3550.
92. Britten, C.D.; Rowinsky, E.K.; Soignet, S.; et al. A phase I and pharmacological study of the farnesyl protein transferase inhibitor L-778,123 in patients with solid malignancies. Clin Cancer Res 2001, 7 (12), 3894-3903.
93. Haas, N.; Peereboom, D.; Ranganathan, S.; Thistle, A.; Greenberg, R.; Ross, E.; Lewis, N.; Wright, J.; Hudes, G. Phase II trial of R115777, an inhibitor of farnesyltransferase, in patients with hormone refractory prostate cancer. Proc Am Soc Clin Oncol 2002, 21, (abstract 271).
94. Adjei, A.A.; Davis, J.N.; Erlichman, C.; Svingen, P.A.; Kaufmann, S.H. Comparison of potential markers of farnesyltransferase inhibition. Clin Cancer Res 2000, 6 (6), 2318-2325.
95. Moasser, M.M.; Rosen, N. The use of molecular markers in farnesyltransferase inhibitor (FTI) therapy of breast cancer. Breast Cancer Res Treat 2002, 73 (2), 135-144.
96. Hu, W.; Wu, W.; Verschraegen, C.F.; et al. Proteomic identification of heat shock protein 70 as a candidate target for enhancing apoptosis induced by farnesyl transferase inhibitor. Proteomics 2003, 3 (10), 1904-1911.
97. Raponi, M.; Belly, R.T.; Karp, J.E.; Lancet, J.E.; Atkins, D.; Wang, Y. Microarray analysis reveals genetic pathways modulated by tipifarnib in acute myeloid leukemia. BMC Cancer 2004, 4 (56), 1-12. http: www.biomedcentral.com/1471-2407/4/56.