title: A new aurora in anaplastic thyroid cancer therapy.
abstract: Anaplastic thyroid cancers (ATC) are among the most aggressive human neoplasms with a dire prognosis and a median survival time of few months from the diagnosis. The complete absence of effective therapies for ATC renders the identification of novel therapeutic approaches sorely needed. Chromosomal instability, a feature of all human cancers, is thought to represent a major driving force in thyroid cancer progression and a number of mitotic kinases showing a deregulated expression in malignant thyroid tissues are now held responsible for thyroid tumor aneuploidy. These include the three members of the Aurora family (Aurora-A, Aurora-B, and Aurora-C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. Over the last few years, several small molecule inhibitors targeting Aurora kinases were developed, which showed promising antitumor effects against a variety of human cancers, including ATC, in preclinical studies. Several of these molecules are now being evaluated in phase I/II clinical trials against advanced solid and hematological malignancies. In the present review we will describe the structure, expression, and mitotic functions of the Aurora kinases, their implications in human cancer progression, with particular regard to ATC, and the effects of their functional inhibition on malignant cell proliferation.
authors.affiliation: Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Enke
authors.initials: E
authors.lastname: Baldini
authors.affiliation: Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Massimino
authors.initials: M
authors.lastname: D'Armiento
authors.affiliation: Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Salvatore
authors.identifier: 0000-0002-7573-0759
authors.initials: S
authors.lastname: Ulisse
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2803-8
references.pmid: 17296934
references.citation: Exp Cell Res. 2000 May 25;257(1):11-21
references.pmid: 10854050
references.citation: Oncogene. 2006 Aug 10;25(35):4831-9
references.pmid: 16532023
references.citation: Br J Cancer. 2012 Feb 14;106(4):748-55
references.pmid: 22240781
references.citation: Cell Cycle. 2007 Oct 15;6(20):2579-80
references.pmid: 18309533
references.citation: Genetics. 1993 Nov;135(3):677-91
references.pmid: 8293973
references.citation: Curr Biol. 2002 Apr 16;12(8):640-7
references.pmid: 11967150
references.citation: Oncogene. 2005 Nov 10;24(49):7266-72
references.pmid: 16027732
references.citation: Biochem Biophys Res Commun. 2004 Apr 9;316(3):930-6
references.pmid: 15033491
references.citation: Cell Mol Life Sci. 2013 Feb;70(4):661-87
references.pmid: 22864622
references.citation: FEBS Lett. 2001 Nov 9;508(1):149-52
references.pmid: 11707286
references.citation: Curr Opin Oncol. 2003 Jan;15(1):78-83
references.pmid: 12490766
references.citation: Cancer Cell. 2003 Jan;3(1):51-62
references.pmid: 12559175
references.citation: Clin Endocrinol (Oxf). 2012 Nov;77(5):780-6
references.pmid: 22702340
references.citation: Andrologia. 2010 Aug;42(4):260-7
references.pmid: 20629650
references.citation: Med Res Rev. 2011 Sep;31(5):757-93
references.pmid: 20196102
references.citation: Nat Rev Mol Cell Biol. 2003 Nov;4(11):842-54
references.pmid: 14625535
references.citation: Cell Cycle. 2009 Sep 15;8(18):2984-94
references.pmid: 19713763
references.citation: Cancer Control. 2006 Apr;13(2):119-28
references.pmid: 16735986
references.citation: Expert Opin Ther Pat. 2011 Jun;21(6):857-84
references.pmid: 21591849
references.citation: Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):21022-7
references.pmid: 21097701
references.citation: J Cell Biol. 2005 Sep 26;170(7):1047-55
references.pmid: 16172205
references.citation: BMC Cancer. 2011 Sep 26;11:411
references.pmid: 21943074
references.citation: Exp Cell Res. 2012 Jul 15;318(12):1407-20
references.pmid: 22472345
references.citation: J Biol Chem. 2002 Mar 22;277(12):10719-26
references.pmid: 11790771
references.citation: Cancer Res. 2002 Sep 15;62(18):5168-77
references.pmid: 12234980
references.citation: PLoS One. 2011;6(10):e26512
references.pmid: 22046298
references.citation: Mod Pathol. 2011 Jun;24(6):836-45
references.pmid: 21441901
references.citation: CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49
references.pmid: 19474385
references.citation: Clin Ter. 2012;163(5):e307-13
references.pmid: 23099978
references.citation: Endocr Relat Cancer. 2008 Jun;15(2):559-68
references.pmid: 18430894
references.citation: J Biol Chem. 2009 Nov 27;284(48):33177-84
references.pmid: 19801554
references.citation: J Clin Endocrinol Metab. 2005 Feb;90(2):928-35
references.pmid: 15562011
references.citation: J Cell Biol. 2006 Jun 19;173(6):833-7
references.pmid: 16769825
references.citation: J Biol Regul Homeost Agents. 2013 Jul-Sep;27(3):705-15
references.pmid: 24152827
references.citation: J Clin Endocrinol Metab. 2011 Feb;96(2):504-8
references.pmid: 21106716
references.citation: Nat Rev Genet. 2012 Jan 24;13(3):189-203
references.pmid: 22269907
references.citation: Cell Motil Cytoskeleton. 2004 Dec;59(4):249-63
references.pmid: 15499654
references.citation: FASEB J. 2009 Aug;23(8):2741-8
references.pmid: 19332642
references.citation: Endocr Relat Cancer. 2011 Jan 13;18(1):129-41
references.pmid: 21071467
references.citation: Mol Genet Metab. 2001 Feb;72(2):155-63
references.pmid: 11161841
references.citation: Cell. 1995 Apr 7;81(1):95-105
references.pmid: 7720077
references.citation: Thyroid. 2006 Nov;16(11):1151-5
references.pmid: 17123342
references.citation: Nat Rev Mol Cell Biol. 2007 Oct;8(10):798-812
references.pmid: 17848966
references.citation: Environ Mol Mutagen. 2009 Oct;50(8):602-19
references.pmid: 19774610
references.citation: J Biol Chem. 1999 Mar 12;274(11):7334-40
references.pmid: 10066797
references.citation: Curr Opin Otolaryngol Head Neck Surg. 2014 Apr;22(2):121-6
references.pmid: 24492853
references.citation: Int J Biochem Cell Biol. 2005 Aug;37(8):1572-7
references.pmid: 15896667
references.citation: Breast Cancer Res Treat. 2013 Aug;140(3):505-17
references.pmid: 23925655
references.citation: Endocr Relat Cancer. 2004 Mar;11(1):131-9
references.pmid: 15027890
references.citation: Nat Rev Endocrinol. 2011 Aug 30;7(10):569-80
references.pmid: 21878896
references.citation: Cancer Sci. 2011 Apr;102(4):762-8
references.pmid: 21214672
references.citation: Am J Pathol. 2002 Nov;161(5):1549-56
references.pmid: 12414503
references.citation: Mol Cell Biol. 2001 Apr;21(8):2944-55
references.pmid: 11283271
references.citation: J Pathol. 2011 Oct;225(2):243-54
references.pmid: 21710690
references.citation: Br J Cancer. 2012 May 22;106(11):1798-806
references.pmid: 22538974
references.citation: Nat Rev Drug Discov. 2009 Jul;8(7):547-66
references.pmid: 19568282
references.citation: Science. 2008 Jun 20;320(5883):1655-8
references.pmid: 18566290
references.citation: Clin Ter. 2012 Nov;163(6):e457-62
references.pmid: 23306762
references.citation: Cell Death Differ. 2012 Mar;19(3):369-77
references.pmid: 22223105
references.citation: Development. 1998 Nov;125(22):4391-402
references.pmid: 9778499
references.citation: J Cell Biol. 2005 Sep 26;170(7):1039-46
references.pmid: 16186253
references.citation: J Cell Biol. 1998 Dec 14;143(6):1635-46
references.pmid: 9852156
references.citation: Mol Cell Biochem. 2003 Dec;254(1-2):157-62
references.pmid: 14674694
references.citation: Thyroid. 2004 Nov;14(11):881-8
references.pmid: 15671765
references.citation: Int J Cancer. 2006 Jul 15;119(2):275-82
references.pmid: 16477625
references.citation: Cell Cycle. 2012 Feb 1;11(3):489-502
references.pmid: 22274399
references.citation: Anticancer Drugs. 2010 Apr;21(4):339-50
references.pmid: 20016367
references.citation: Lancet. 2003 Feb 8;361(9356):501-11
references.pmid: 12583960
references.citation: J Biol Chem. 1997 Apr 4;272(14):9166-74
references.pmid: 9083047
references.citation: Oncol Rep. 2011 Jul;26(1):23-32
references.pmid: 21479365
references.citation: Ann Surg Oncol. 2007 Feb;14(2):719-29
references.pmid: 17115102
references.citation: Cancer Res. 2011 May 1;71(9):3225-35
references.pmid: 21521802
references.citation: Invest New Drugs. 2012 Dec;30(6):2411-32
references.pmid: 22350019
references.citation: Eur J Cancer. 2006 Oct;42(15):2631-8
references.pmid: 16928445
references.citation: Biochem Biophys Res Commun. 2011 May 20;408(4):647-53
references.pmid: 21531210
references.citation: Curr Opin Cell Biol. 2005 Oct;17(5):548-58
references.pmid: 16098727
references.citation: Int J Immunopathol Pharmacol. 2011 Jan-Mar;24(1):79-88
references.pmid: 21496390
references.citation: PLoS One. 2011;6(6):e21436
references.pmid: 21731748
references.citation: J Biol Chem. 2010 Jul 9;285(28):21849-57
references.pmid: 20444701
references.citation: Sci Transl Med. 2013 Jan 2;5(166):166ra3
references.pmid: 23283368
references.citation: Anticancer Agents Med Chem. 2012 Jan;12(1):87-93
references.pmid: 22043992
references.citation: Diagn Pathol. 2012 Jul 18;7:84
references.pmid: 22809428
references.citation: Oncogene. 2002 Aug 15;21(36):5619-30
references.pmid: 12165861
references.citation: Mol Cancer Res. 2008 Dec;6(12):1937-45
references.pmid: 19074838
references.citation: J Clin Endocrinol Metab. 2012 Sep;97(9):3179-84
references.pmid: 22774206
references.citation: EMBO J. 1995 Sep 15;14(18):4514-22
references.pmid: 7556094
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Crit Rev Oncol Hematol. 2010 Feb;73(2):99-110
references.pmid: 19369091
references.citation: Oncol Lett. 2012 Jun;3(6):1237-1244
references.pmid: 22783425
references.citation: Lancet Oncol. 2010 Oct;11(10):962-72
references.pmid: 20851682
references.citation: Oncologist. 2009 Aug;14(8):780-93
references.pmid: 19684075
references.citation: Mol Cancer Ther. 2010 Feb;9(2):268-78
references.pmid: 20124450
references.citation: Endocrine. 2012 Dec;42(3):637-46
references.pmid: 22477151
references.citation: EMBO J. 1998 Jun 1;17(11):3052-65
references.pmid: 9606188
references.citation: Br J Cancer. 2004 Jan 26;90(2):492-6
references.pmid: 14735198
references.citation: BMC Surg. 2013;13 Suppl 2:S44
references.pmid: 24267151
references.citation: Trends Cell Biol. 1999 Nov;9(11):454-9
references.pmid: 10511710
references.citation: EMBO Rep. 2002 May;3(5):457-62
references.pmid: 11964384
references.citation: Expert Rev Anticancer Ther. 2006 Jan;6(1):109-20
references.pmid: 16375648
references.citation: Nat Rev Cancer. 2005 Jan;5(1):42-50
references.pmid: 15630414
references.citation: J Cell Sci. 2004 May 15;117(Pt 12):2523-31
references.pmid: 15128871
references.citation: Cell Death Differ. 2012 Dec;19(12):1992-2002
references.pmid: 22790872
references.citation: Oncogene. 2005 Feb 3;24(6):1122-7
references.pmid: 15592510
references.citation: Endocr Relat Cancer. 2007 Sep;14(3):827-37
references.pmid: 17914111
references.citation: Int J Cancer. 2013 Feb 1;132(3):509-20
references.pmid: 22729867
references.citation: J Clin Endocrinol Metab. 2006 Jan;91(1):313-9
references.pmid: 16263822
references.citation: BMC Cancer. 2010 Aug 28;10:461
references.pmid: 20799978