title: Tipifarnib in the treatment of acute myeloid leukemia.
abstract: Farnesyltransferase inhibitors (FTIs) are a new class of biologically active anticancer drugs. The exact anti-tumorigenic mechanism is currently unknown. FTIs inhibit farnesylation of a wide range of target proteins. In preclinical models, tipifarnib (R115777, Zarnestra(R)), a non-peptidomimetic competitive FTI, showed great potency against leukemic cells. Although it has recently demonstrated clinical responses in adults with refractory and relapsed acute myeloid leukemia (AML), and in older adults with newly diagnosed poor-risk AML, its activity was far less than anticipated. However, it appears that tipifarnib as a single agent may be important in selected groups of patients. Much remains to be learned to optimize such therapy in patients with AML. To this end, trials that combine tipifarnib with cytotoxics are ongoing.
authors.affiliation: Hematology, Edouard Herriot Hospital, Lyon, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.forename: Mohamed
authors.initials: M
authors.lastname: Elhamri
references.citation: Blood. 2003 Dec 1;102(12):3880-9
references.pmid: 12920034
references.citation: Biochemistry. 1998 May 12;37(19):6924-38
references.pmid: 9578579
references.citation: Cell. 1992 Dec 24;71(7):1143-55
references.pmid: 1473150
references.citation: Cancer Res. 2001 Jan 1;61(1):131-7
references.pmid: 11196150
references.citation: Cancer. 2006 Mar 1;106(5):1090-8
references.pmid: 16435386
references.citation: J Clin Oncol. 2004 Dec 1;22(23):4816-22
references.pmid: 15570084
references.citation: Mol Cell Biol. 1998 Oct;18(10):5699-711
references.pmid: 9742087
references.citation: J Biol Chem. 1997 Apr 11;272(15):10232-9
references.pmid: 9092572
references.citation: Cancer Res. 1994 Jun 15;54(12):3229-32
references.pmid: 8205544
references.citation: Cell Growth Differ. 1992 Jul;3(7):461-9
references.pmid: 1419908
references.citation: Curr Top Med Chem. 2003;3(10):1095-102
references.pmid: 12769710
references.citation: N Engl J Med. 1999 Sep 30;341(14):1051-62
references.pmid: 10502596
references.citation: Hematol Oncol Clin North Am. 2000 Feb;14(1):251-67
references.pmid: 10680081
references.citation: Nature. 1995 Aug 17;376(6541):599-602
references.pmid: 7637810
references.citation: Mol Cancer Ther. 2005 Jun;4(6):918-26
references.pmid: 15956249
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15356-61
references.pmid: 9860973
references.citation: J Cell Biol. 1997 Oct 20;139(2):435-47
references.pmid: 9334346
references.citation: Blood. 2007 Feb 15;109(4):1387-94
references.pmid: 17082323
references.citation: Blood. 1999 Mar 15;93(6):2043-56
references.pmid: 10068678
references.citation: Cell. 1992 Aug 7;70(3):389-99
references.pmid: 1643657
references.citation: Cancer Res. 2003 Sep 15;63(18):5656-68
references.pmid: 14522880
references.citation: J Clin Oncol. 1999 Nov;17(11):3631-52
references.pmid: 10550163
references.citation: J Clin Oncol. 2004 Apr 1;22(7):1287-92
references.pmid: 15051776
references.citation: Annu Rev Biochem. 1993;62:851-91
references.pmid: 8352603
references.citation: Blood. 2006 May 1;107(9):3481-5
references.pmid: 16455952
references.citation: Invest New Drugs. 1999;17(3):241-58
references.pmid: 10665477
references.citation: Blood. 1997 Nov 1;90(9):3322-31
references.pmid: 9345014
references.citation: Blood. 2007 Jun 15;109(12):5151-6
references.pmid: 17351110
references.citation: Curr Opin Pharmacol. 2002 Aug;2(4):388-93
references.pmid: 12127871
references.citation: Mol Reprod Dev. 1995 Dec;42(4):459-67
references.pmid: 8607977
references.citation: Anticancer Drugs. 2001 Mar;12(3):193-7
references.pmid: 11290865
references.citation: Blood. 2001 Jun 1;97(11):3361-9
references.pmid: 11369625
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12479-84
references.pmid: 15308774
references.citation: Cell Signal. 2004 Oct;16(10):1105-12
references.pmid: 15240005
references.citation: Mol Cell Biol. 2001 Oct;21(20):6906-12
references.pmid: 11564874
references.citation: J Biol Chem. 2002 Nov 29;277(48):46659-68
references.pmid: 12235145
references.citation: Blood. 1997 May 1;89(9):3323-9
references.pmid: 9129038
references.citation: Blood. 2007 May 15;109(10):4158-63
references.pmid: 17264294
references.citation: Science. 1999 Nov 12;286(5443):1358-62
references.pmid: 10558990
references.citation: J Clin Oncol. 2000 Feb;18(4):927-41
references.pmid: 10673536
references.citation: Cancer Res. 1997 Feb 15;57(4):708-13
references.pmid: 9044849
references.citation: Anticancer Drugs. 2005 Mar;16(3):317-21
references.pmid: 15711184
references.citation: Nature. 1993 Dec 16;366(6456):643-54
references.pmid: 8259209
references.citation: Cancer Res. 2005 Apr 15;65(8):3117-25
references.pmid: 15833841
references.citation: Trends Cell Biol. 2000 Mar;10(3):85-8
references.pmid: 10675900
references.citation: J Cell Biol. 1995 Aug;130(3):507-18
references.pmid: 7542657
references.citation: J Biol Chem. 1997 May 30;272(22):14459-64
references.pmid: 9162087
references.citation: Blood. 2003 Dec 15;102(13):4527-34
references.pmid: 12947010
references.citation: J Biol Chem. 2000 Sep 29;275(39):30451-7
references.pmid: 10852915
references.citation: Cancer Res. 1999 Nov 1;59(21):5492-6
references.pmid: 10554025
references.citation: Clin Cancer Res. 2007 Apr 1;13(7):2254-60
references.pmid: 17404110
references.citation: BMC Cancer. 2004 Aug 25;4:56
references.pmid: 15329151
references.citation: J Lipid Res. 2006 Jan;47(1):15-31
references.pmid: 16278491
references.citation: Leukemia. 2000 Mar;14(3):480-7
references.pmid: 10720146
references.citation: Cancer Res. 2004 Nov 15;64(22):8389-96
references.pmid: 15548709
references.citation: Exp Cell Res. 2004 Nov 15;301(1):43-9
references.pmid: 15501444
references.citation: Blood. 2005 Jun 15;105(12):4759-66
references.pmid: 15728126
references.citation: J Biol Chem. 2005 Sep 2;280(35):31101-8
references.pmid: 16006564
references.citation: Cancer Res. 1989 Sep 1;49(17):4682-9
references.pmid: 2547513
references.citation: J Biol Chem. 1997 Jun 20;272(25):15591-4
references.pmid: 9188444
references.citation: Leukemia. 2003 Aug;17(8):1482-98
references.pmid: 12886235
references.citation: J Clin Oncol. 2002 Jun 1;20(11):2726-35
references.pmid: 12039935
references.citation: Cancer Lett. 1996 Dec 20;110(1-2):49-55
references.pmid: 9018080