title: New agents in acute myeloid leukemia: beyond cytarabine and anthracyclines.
abstract: The standard therapeutic approaches for acute myeloid leukemia (AML) continue to be based on anthracyclines and cytarabine. However, the prognosis for AML remains poor, especially for patients with high-risk disease. During the past decade, promising novel agents that target DNA replication and repair, as well as cell cycling and apoptosis, have been developed and are being actively investigated in AML. Among these agents is flavopiridol, which interferes with key steps of the cell cycle and effectively promotes cell death, and voreloxin, an intercalating agent that also targets topoisomerase II. Also under clinical study in AML are oligonucleotide antisense constructs, which suppress the translation of proteins essential for leukemic blast survival and proliferation, and agents that target antiapoptotic cascades. In summary, it is hoped that novel therapies such as these will augment and/or supplant our current cytarabine- and anthracycline-based approaches, overcome active drug-resistance pathways, and eventually improve outcomes for patients with AML.
authors.affiliation: Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, 1650 Orleans Street, CRB 1 Room 289, Baltimore, MD 21231, USA.
authors.forename: Amir T
authors.initials: AT
authors.lastname: Fathi
authors.forename: Judith E
authors.initials: JE
authors.lastname: Karp
mesh_terms: D000208:Acute Disease; D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D003561:Cytarabine / Q000627:therapeutic use; D005419:Flavonoids / Q000627:therapeutic use; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D010880:Piperidines / Q000627:therapeutic use
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; D003561:Cytarabine; C077990:alvocidib
references.citation: Crit Rev Oncol Hematol. 2001 May;38(2):139-70
references.pmid: 11311660
references.citation: Leukemia. 2006 Jun;20(6):911-28
references.pmid: 16642045
references.citation: Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4467-73
references.pmid: 17671131
references.citation: Hematology Am Soc Hematol Educ Program. 2001;:443-62
references.pmid: 11722998
references.citation: Blood. 1998 Nov 15;92(10):3804-16
references.pmid: 9808574
references.citation: Semin Oncol. 1997 Feb;24(1):103-13
references.pmid: 9045296
references.citation: Blood. 2005 Aug 15;106(4):1154-63
references.pmid: 15870183
references.citation: Clin Cancer Res. 2008 May 15;14(10):3077-82
references.pmid: 18483374
references.citation: N Engl J Med. 1999 Sep 30;341(14):1051-62
references.pmid: 10502596
references.citation: Clin Cancer Res. 2008 May 1;14(9):2756-62
references.pmid: 18451242
references.citation: Leuk Res. 2008 Oct;32(10):1633-4
references.pmid: 18405970
references.citation: Blood. 2003 Jan 15;101(2):425-32
references.pmid: 12393493
references.citation: Leukemia. 2008 Jan;22(1):147-60
references.pmid: 17928881
references.citation: Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14036-40
references.pmid: 8943056
references.citation: Leukemia. 2003 May;17(5):995-7
references.pmid: 12750723
references.citation: Blood. 2005 Mar 15;105(6):2527-34
references.pmid: 15550488
references.citation: Leukemia. 2003 Nov;17(11):2157-67
references.pmid: 12931221
references.citation: Curr Opin Investig Drugs. 2008 Jun;9(6):638-46
references.pmid: 18516763
references.citation: Ann Oncol. 2005 Apr;16(4):525-37
references.pmid: 15728109
references.citation: Clin Biochem. 1998 Jul;31(5):335-40
references.pmid: 9721431
references.citation: Curr Treat Options Oncol. 2006 Jul;7(4):285-94
references.pmid: 16916489
references.citation: Cancer Chemother Pharmacol. 2009 Jun;64(1):53-65
references.pmid: 18931998
references.citation: Biochem Biophys Res Commun. 2004 Jan 9;313(2):443-6
references.pmid: 14684182
references.citation: J Clin Oncol. 2005 May 20;23(15):3404-11
references.pmid: 15824414
references.citation: Cancer Res. 1999 Nov 1;59(21):5433-7
references.pmid: 10554012
references.citation: Antisense Nucleic Acid Drug Dev. 2002 Jun;12(3):193-213
references.pmid: 12162702
references.citation: Ann N Y Acad Sci. 2005 Nov;1058:215-34
references.pmid: 16394139
references.citation: J Biol Chem. 2001 Aug 24;276(34):31793-9
references.pmid: 11431468
references.citation: Clin Cancer Res. 2003 Jan;9(1):307-15
references.pmid: 12538483
references.citation: Blood. 2003 Jul 15;102(2):442-8
references.pmid: 12560224
references.citation: Clin Cancer Res. 2006 Sep 1;12(17):5165-73
references.pmid: 16951235
references.citation: Nat Rev Drug Discov. 2005 Dec;4(12):988-1004
references.pmid: 16341064
references.citation: Clin Cancer Res. 2008 Jun 15;14(12):3889-95
references.pmid: 18559610
references.citation: Cancer Res. 2005 Nov 1;65(21):9643-50
references.pmid: 16266983
references.citation: Clin Cancer Res. 2005 Dec 1;11(23):8403-12
references.pmid: 16322302
references.citation: Blood. 1993 Jun 1;81(11):3091-6
references.pmid: 7684624
references.citation: Clin Adv Hematol Oncol. 2005 Apr;3(4):287-96, 302
references.pmid: 16167001
references.citation: Cancer Res. 1997 Aug 15;57(16):3375-80
references.pmid: 9269999
references.citation: Cell Death Differ. 2001 Jul;8(7):715-24
references.pmid: 11464216
references.citation: Blood. 2007 Jan 15;109(2):399-404
references.pmid: 17003373
references.citation: Ann Oncol. 1998 Feb;9(2):159-65
references.pmid: 9553660
references.citation: Blood Rev. 1997 Dec;11(4):201-23
references.pmid: 9481450