title: Inflammatory stress and sarcomagenesis: a vicious interplay.
abstract: Chronic inflammation represents one of the hallmarks of cancer, but its role in sarcomagenesis has long been overlooked. Sarcomas are a rare and heterogeneous group of tumors of mesenchymal origin accounting for less than 1 % of cancers in adults but 21 % of cancers in the pediatric population. Sarcomas are associated with bad prognosis, and their management requires a multidisciplinary team approach. Several lines of evidence indicate that inflammation has been implicated in sarcomagenesis leading to the activation of the key transcription factors HIF-1, NF- κB, and STAT-3 involved in a complex inflammatory network. In the past years, an increasing number of new targets have been identified in the treatment of sarcomas leading to the development of new drugs that aim to interrupt the vicious connection between inflammation and sarcomagenesis. This article makes a brief overview of preclinical and clinical evidence of the molecular pathways involved in the inflammatory stress response in sarcomagenesis and the most targeted therapies.
authors.affiliation: multimmune GmbH c/o Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany, raj10062@web.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Radons
mesh_terms: D063646:Carcinogenesis; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012509:Sarcoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D018836:Inflammation Mediators; D047428:Protein Kinase Inhibitors; D014157:Transcription Factors
references.citation: Toxicol Appl Pharmacol. 2006 Oct 1;216(1):11-9
references.pmid: 16797629
references.citation: J Pathol. 2011 Oct;225(2):195-202
references.pmid: 21547906
references.citation: Mol Cell Biol. 2004 Aug;24(16):7275-83
references.pmid: 15282325
references.citation: Mar Drugs. 2012 Aug;10(8):1852-1872
references.pmid: 23015777
references.citation: J Cell Commun Signal. 2009 Dec;3(3-4):311-22
references.pmid: 19798593
references.citation: J Virol. 2012 Jun;86(11):5974-91
references.pmid: 22438557
references.citation: Cell Cycle. 2012 Apr 1;11(7):1393-9
references.pmid: 22421142
references.citation: J Clin Endocrinol Metab. 2010 Oct;95(10):E181-91
references.pmid: 20668041
references.citation: Clin Cancer Res. 2012 May 1;18(9):2638-47
references.pmid: 22374332
references.citation: J Cell Biochem. 2010 May 15;110(2):438-46
references.pmid: 20225273
references.citation: Cancer Cell. 2004 Nov;6(5):447-58
references.pmid: 15542429
references.citation: J Am Acad Dermatol. 2012 Dec;67(6):1335-41
references.pmid: 22677489
references.citation: Semin Cancer Biol. 2012 Feb;22(1):33-40
references.pmid: 22210179
references.citation: Gynecol Oncol. 2012 Nov;127(2):356-61
references.pmid: 22796461
references.citation: Blood. 2005 May 15;105(10):3987-94
references.pmid: 15665117
references.citation: Clin Cancer Res. 2010 May 1;16(9):2512-7
references.pmid: 20388853
references.citation: Nature. 2009 Nov 5;462(7269):44-5
references.pmid: 19890318
references.citation: Anticancer Drugs. 2012 Jul;23(6):638-50
references.pmid: 22382389
references.citation: Int J Mol Med. 2006 Apr;17(4):661-8
references.pmid: 16525725
references.citation: J Cell Physiol. 2009 Oct;221(1):98-108
references.pmid: 19475568
references.citation: Sarcoma. 2012;2012:152382
references.pmid: 22550413
references.citation: Blood. 2005 Jun 15;105(12):4784-91
references.pmid: 15731178
references.citation: Oncogene. 2011 Apr 7;30(14):1615-30
references.pmid: 21170083
references.citation: Nat Rev Cancer. 2008 Dec;8(12):915-28
references.pmid: 19029956
references.citation: Clin Cancer Res. 2011 Feb 1;17(3):505-13
references.pmid: 21177409
references.citation: Cell Biol Int. 2004;28(10):653-60
references.pmid: 15516323
references.citation: J Clin Invest. 2009 Aug;119(8):2366-78
references.pmid: 19620785
references.citation: BMC Cancer. 2012 Apr 02;12:131
references.pmid: 22471890
references.citation: ISRN Oncol. 2013;2013:759725
references.pmid: 23346417
references.citation: Cell. 2004 Nov 24;119(5):591-602
references.pmid: 15550242
references.citation: Br J Cancer. 2007 Oct 22;97(8):1084-9
references.pmid: 17940501
references.citation: J Clin Oncol. 2003 Dec 1;21(23):4342-9
references.pmid: 14645423
references.citation: Ann Oncol. 2001 Jan;12(1):75-80
references.pmid: 11249053
references.citation: Sarcoma. 2011;2011:260757
references.pmid: 21559261
references.citation: Cancer. 2012 Mar 15;118(6):1486-97
references.pmid: 21837674
references.citation: Cancer Res. 2008 Nov 1;68(21):8733-42
references.pmid: 18974115
references.citation: Med Hypotheses. 2012 Jul;79(1):98-100
references.pmid: 22546756
references.citation: Anticancer Res. 2012 Dec;32(12):5139-50
references.pmid: 23225410
references.citation: Eur J Cell Biol. 2011 Jun-Jul;90(6-7):545-52
references.pmid: 21112119
references.citation: Trends Cell Biol. 2013 Sep;23(9):421-32
references.pmid: 23685018
references.citation: Cancer Res. 2006 Aug 1;66(15):7445-52
references.pmid: 16885340
references.citation: Free Radic Biol Med. 2012 May 1;52(9):2013-37
references.pmid: 22391222
references.citation: J Pediatr Surg. 2011 Jan;46(1):108-14
references.pmid: 21238650
references.citation: Pediatr Blood Cancer. 2011 Dec 1;57(6):943-9
references.pmid: 21793180
references.citation: Int J Mol Med. 2006 Feb;17(2):377-83
references.pmid: 16391840
references.citation: J Cell Biochem. 2010 Sep 1;111(1):130-7
references.pmid: 20506157
references.citation: J Biol Chem. 2009 Oct 23;284(43):29596-604
references.pmid: 19710019
references.citation: PLoS One. 2010 Aug 23;5(8):e12358
references.pmid: 20808805
references.citation: Gynecol Oncol. 2011 Jul;122(1):141-8
references.pmid: 21450334
references.citation: J Pathol. 2011 Jan;223(1):72-80
references.pmid: 21125666
references.citation: N Engl J Med. 2010 Oct 28;363(18):1727-33
references.pmid: 20979472
references.citation: Expert Rev Anticancer Ther. 2009 Aug;9(8):1135-44
references.pmid: 19671033
references.citation: Cancer Res. 2005 Jul 1;65(13):5535-43
references.pmid: 15994925
references.citation: Cell Div. 2010 May 13;5:12
references.pmid: 20465818
references.citation: BMC Genomics. 2007 Mar 14;8:73
references.pmid: 17359542
references.citation: J Pathol. 2008 Dec;216(4):428-39
references.pmid: 18855347
references.citation: Immunobiology. 2000 Jan;201(3-4):368-76
references.pmid: 10776793
references.citation: Immunology. 2011 Jan;132(1):39-48
references.pmid: 20722758
references.citation: Acta Obstet Gynecol Scand. 2010;89(1):120-5
references.pmid: 19900134
references.citation: J Clin Immunol. 2013 Jan;33 Suppl 1:S79-84
references.pmid: 23225204
references.citation: Cancer Res. 2008 Jun 15;68(12):4727-35
references.pmid: 18559519
references.citation: Nat Rev Cancer. 2009 Nov;9(11):798-809
references.pmid: 19851315
references.citation: Blood. 2001 Nov 1;98(9):2603-14
references.pmid: 11675328
references.citation: Front Immunol. 2012 Jan 12;2:98
references.pmid: 22566887
references.citation: Ann N Y Acad Sci. 2007 Oct;1113:178-91
references.pmid: 17483209
references.citation: J Surg Oncol. 2003 Nov;84(3):151-9
references.pmid: 14598359
references.citation: Cell Res. 2007 Aug;17(8):666-81
references.pmid: 17680028
references.citation: Cancer Res. 2012 May 15;72(10):2501-11
references.pmid: 22461510
references.citation: Pediatr Blood Cancer. 2013 Mar;60(3):409-14
references.pmid: 23065953
references.citation: PLoS Pathog. 2010 Feb 12;6(2):e1000777
references.pmid: 20169190
references.citation: Curr Opin Pharmacol. 2009 Aug;9(4):351-69
references.pmid: 19665429
references.citation: ORL J Otorhinolaryngol Relat Spec. 2000 Sep-Oct;62(5):257-65
references.pmid: 10965261
references.citation: J Cutan Med Surg. 2002 Jan-Feb;6(1):29-34
references.pmid: 11896422
references.citation: Histopathology. 2011 Sep;59(3):556-61
references.pmid: 22034893
references.citation: Int J Cancer. 2006 Dec 15;119(12):2922-30
references.pmid: 17013893
references.citation: Mod Pathol. 1999 Aug;12(8):775-80
references.pmid: 10463479
references.citation: Cancer Lett. 2011 Oct 28;309(2):145-50
references.pmid: 21683519
references.citation: Int J Cancer. 2002 Sep 1;101(1):11-6
references.pmid: 12209582
references.citation: Surg Clin North Am. 2008 Jun;88(3):451-81, v
references.pmid: 18514694
references.citation: PLoS One. 2012;7(6):e39679
references.pmid: 22768106
references.citation: Otol Neurotol. 2002 Sep;23(5):647-52
references.pmid: 12218613
references.citation: Carcinogenesis. 2009 Jul;30(7):1073-81
references.pmid: 19468060
references.citation: Cancer Lett. 2003 Jul 30;198(1):107-17
references.pmid: 12893437
references.citation: Eur J Dermatol. 2005 Nov-Dec;15(6):465-9
references.pmid: 16280300
references.citation: Acta Haematol. 1991;85(2):93-9
references.pmid: 1850944
references.citation: Trends Mol Med. 2010 Jan;16(1):37-45
references.pmid: 20031486
references.citation: J Immunol. 1992 May 15;148(10):3140-6
references.pmid: 1315829
references.citation: Oncogene. 2012 Nov 15;31(46):4835-47
references.pmid: 22266868
references.citation: Int J Oncol. 2012 Aug;41(2):753-8
references.pmid: 22641358
references.citation: Arch Toxicol. 2013 Jan;87(1):19-48
references.pmid: 22885793
references.citation: Cancer Sci. 2007 Feb;98(2):163-8
references.pmid: 17233833
references.citation: Transl Biomed. 2010;1(2):
references.pmid: 23082307
references.citation: Ann Oncol. 2013 Jan;24(1):252-7
references.pmid: 22898035
references.citation: Cancer Res. 2007 Aug 1;67(15):7247-55
references.pmid: 17671193
references.citation: PLoS One. 2011;6(11):e28200
references.pmid: 22140545
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3501-6
references.pmid: 23382202
references.citation: Cancer Res. 2012 Apr 1;72(7):1751-62
references.pmid: 22350414
references.citation: Oncol Rep. 2007 Nov;18(5):1165-9
references.pmid: 17914567
references.citation: Pathol Int. 2001 Sep;51(9):739-43
references.pmid: 11696180
references.citation: Mol Cancer Ther. 2008 Jul;7(7):1807-16
references.pmid: 18644993
references.citation: Cytokine. 2002 Sep 21;19(6):259-66
references.pmid: 12421568
references.citation: Pathology. 2010;42(5):421-5
references.pmid: 20632817
references.citation: Int J Cancer. 2007 Feb 15;120(4):761-8
references.pmid: 17131322
references.citation: J Cancer Res Clin Oncol. 2000 Nov;126(11):667-70
references.pmid: 11079732
references.citation: Cancer. 2012 Dec 1;118(23):5894-902
references.pmid: 22605650
references.citation: Sarcoma. 2011;2011:130484
references.pmid: 21559212
references.citation: Biochem Biophys Res Commun. 2009 May 8;382(3):514-8
references.pmid: 19285954
references.citation: BMC Cancer. 2006 Dec 19;6:292
references.pmid: 17177986
references.citation: Sarcoma. 2012;2012:849456
references.pmid: 22665999
references.citation: J Cancer Res Clin Oncol. 2011 Jun;137(6):1037-51
references.pmid: 21193997
references.citation: Cell Physiol Biochem. 2012;30(6):1481-90
references.pmid: 23208072
references.citation: Neurosci Res. 2007 May;58(1):50-7
references.pmid: 17331604
references.citation: J Pathol. 2006 May;209(1):114-20
references.pmid: 16482498
references.citation: Genes Dev. 2007 Jul 15;21(14):1714-9
references.pmid: 17639077
references.citation: Cell Stress Chaperones. 2005 Summer;10(2):86-103
references.pmid: 16038406
references.citation: Pathol Res Pract. 2000;196(10):665-73
references.pmid: 11087053
references.citation: Med Oncol. 2010 Dec;27(4):1096-101
references.pmid: 19859844
references.citation: Clin Cancer Res. 2011 Sep 15;17(18):5901-12
references.pmid: 21821699
references.citation: FASEB J. 2010 Sep;24(9):3427-37
references.pmid: 20466878
references.citation: J Surg Res. 2012 Jun 15;175(2):e53-60
references.pmid: 22341347
references.citation: Cell Cycle. 2010 Jun 15;9(12):2310-6
references.pmid: 20519952
references.citation: Acta Reumatol Port. 2011 Jul-Sep;36(3):209-18
references.pmid: 22113597
references.citation: Adv Exp Med Biol. 2007;601:265-70
references.pmid: 17713014
references.citation: Adv Exp Med Biol. 2013;767:123-44
references.pmid: 23161009
references.citation: Carcinogenesis. 2010 Apr;31(4):552-8
references.pmid: 20042639
references.citation: J Virol. 2008 Feb;82(4):1759-76
references.pmid: 18057235
references.citation: BMC Cancer. 2010 Apr 08;10:132
references.pmid: 20377868
references.citation: Sarcoma. 2012;2012:626094
references.pmid: 22701332
references.citation: Nat Genet. 2002 Apr;30(4):406-10
references.pmid: 11865300
references.citation: Neurosci Lett. 2007 Jun 15;420(3):217-22
references.pmid: 17556097
references.citation: Curr Biol. 2009 Oct 13;19(19):1670-6
references.pmid: 19800237
references.citation: Br J Cancer. 2009 Jun 16;100(12):1957-65
references.pmid: 19455146
references.citation: Oncogene. 2008 Mar 27;27(14):2015-26
references.pmid: 17922033
references.citation: Trends Mol Med. 2005 Aug;11(8):353-61
references.pmid: 16002336
references.citation: Eur J Cancer. 2013 Oct;49(15):3219-28
references.pmid: 23835252
references.citation: Int J Cancer. 2002 Apr 10;98(5):707-12
references.pmid: 11920639
references.citation: J Virol. 2006 Jul;80(13):6534-52
references.pmid: 16775340
references.citation: Cell Stress Chaperones. 1997 Jun;2(2):132-9
references.pmid: 9250404
references.citation: Clin Cancer Res. 2007 Dec 15;13(24):7314-21
references.pmid: 18094412
references.citation: Cancer Res. 2008 Oct 1;68(19):7966-74
references.pmid: 18829554
references.citation: J Virol. 2009 Apr;83(7):3342-64
references.pmid: 19158252
references.citation: Bull Exp Biol Med. 2000 Jul;130(7):691-3
references.pmid: 11140588
references.citation: Br J Cancer. 2011 Feb 1;104(3):437-40
references.pmid: 21245867
references.citation: Blood. 2006 Apr 15;107(8):3295-302
references.pmid: 16380446
references.citation: Eur J Cancer. 2013 Feb;49(3):684-95
references.pmid: 23079473
references.citation: FEBS J. 2012 Jun;279(12):2247-59
references.pmid: 22521131
references.citation: Genes Chromosomes Cancer. 2009 Nov;48(11):975-82
references.pmid: 19681119
references.citation: Cancer Biol Ther. 2004 Dec;3(12):1217-24
references.pmid: 15477758
references.citation: J Mol Cell Cardiol. 2010 Feb;48(2):360-6
references.pmid: 19945465
references.citation: Hum Mol Genet. 2005 Aug 1;14(15):2231-9
references.pmid: 15987702
references.citation: Nat Rev Clin Oncol. 2011 Feb;8(2):97-106
references.pmid: 21151206
references.citation: Sci STKE. 2006 Oct 17;2006(357):re13
references.pmid: 17047224
references.citation: Cancer. 2001 Apr 15;91(8):1525-9
references.pmid: 11301401
references.citation: Mol Cancer Ther. 2011 Jun;10(6):1018-27
references.pmid: 21490307
references.citation: Curr Opin Cell Biol. 2010 Apr;22(2):169-76
references.pmid: 19945836
references.citation: Sarcoma. 2011;2011:548151
references.pmid: 21437228
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4908-13
references.pmid: 21383199
references.citation: Virchows Arch. 2008 Feb;452(2):157-67
references.pmid: 18066588
references.citation: Curr Mol Med. 2010 Jun;10(4):369-73
references.pmid: 20455855
references.citation: Blood. 1993 Oct 1;82(7):2038-44
references.pmid: 7691245
references.citation: J Toxicol Environ Health A. 2010;73(5):423-36
references.pmid: 20155583
references.citation: J Int Med Res. 2010 Jul-Aug;38(4):1294-304
references.pmid: 20926002
references.citation: Oncol Rep. 2011 Dec;26(6):1513-7
references.pmid: 21874258
references.citation: Genes Dev. 1999 Nov 15;13(22):2905-27
references.pmid: 10579998
references.citation: Cell. 2006 Oct 6;127(1):157-70
references.pmid: 17018283
references.citation: Oncogene. 2010 Dec 2;29(48):6323-30
references.pmid: 20818440
references.citation: Oncol Rep. 2007 Dec;18(6):1365-71
references.pmid: 17982618
references.citation: Lancet. 2007 May 19;369(9574):1731-41
references.pmid: 17512858
references.citation: Hum Mol Genet. 2009 Apr 15;18(8):1464-70
references.pmid: 19228774
references.citation: J Immunol. 2011 Aug 1;187(3):1254-63
references.pmid: 21705618
references.citation: Am J Otol. 1999 Mar;20(2):158-61
references.pmid: 10100515