title: New strategies in ewing sarcoma: lost in translation?
abstract: Ewing sarcoma is the second most common pediatric malignant bone tumor. Aggressive multimodality therapy has led to an improvement in outcomes, particularly in patients with localized disease. However, therapy-related toxicities are not trivial, and the prognosis for patients with relapsed and/or metastatic disease continues to be poor. In this article, we outline some of the promising therapies that have the potential to change the Ewing sarcoma therapeutic paradigm in the not-too-distant future: insulin-like growth factor receptor inhibitors, targeting of the fusion protein, epigenetic manipulation, PARP inhibitors, and immunotherapy.
authors.affiliation: Authors' Affiliation: Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland arnaldezf@mail.nih.gov.
authors.forename: Fernanda I
authors.initials: FI
authors.lastname: Arnaldez
authors.affiliation: Authors' Affiliation: Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Helman
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D058990:Molecular Targeted Therapy; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors; D012512:Sarcoma, Ewing / Q000276:immunology / Q000378:metabolism / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D017451:Receptors, Somatomedin; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1
references.citation: Cancer. 1973 Apr;31(4):889-93
references.pmid: 4267530
references.citation: Pediatr Blood Cancer. 2011 Apr;56(4):595-603
references.pmid: 21298745
references.citation: Clin Cancer Res. 2006 Nov 15;12(22):6781-90
references.pmid: 17121899
references.citation: PLoS Med. 2007 Apr;4(4):e122
references.pmid: 17425403
references.citation: Oncogene. 2002 Apr 25;21(18):2890-5
references.pmid: 11973649
references.citation: Mol Endocrinol. 2012 Sep;26(9):1603-16
references.pmid: 22798295
references.citation: Clin Cancer Res. 2008 Aug 1;14(15):4850-8
references.pmid: 18676758
references.citation: Crit Rev Oncol Hematol. 2012 Aug;83(2):184-93
references.pmid: 22112692
references.citation: J Mol Recognit. 2013 Jul;26(7):318-29
references.pmid: 23657987
references.citation: Genomics. 1996 Jan 1;31(1):58-64
references.pmid: 8808280
references.citation: J Clin Oncol. 2011 Dec 1;29(34):4534-40
references.pmid: 22025154
references.citation: PLoS One. 2008 Jul 09;3(7):e2634
references.pmid: 18648544
references.citation: J Biol Chem. 1997 Dec 5;272(49):30822-7
references.pmid: 9388225
references.citation: Clin Cancer Res. 2010 Aug 1;16(15):3901-9
references.pmid: 20542985
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5324-9
references.pmid: 19289832
references.citation: J Clin Oncol. 2006 Jan 1;24(1):152-9
references.pmid: 16382125
references.citation: Cancer Res. 2012 Apr 1;72(7):1608-13
references.pmid: 22287547
references.citation: J Clin Oncol. 2010 Aug 1;28(22):3623-9
references.pmid: 20606092
references.citation: Annu Rev Pathol. 2012;7:145-59
references.pmid: 21942527
references.citation: Clin Cancer Res. 2007 Feb 15;13(4):1322-30
references.pmid: 17317844
references.citation: N Engl J Med. 2012 Jun 28;366(26):2443-54
references.pmid: 22658127
references.citation: Pediatr Blood Cancer. 2008 Sep;51(3):334-8
references.pmid: 18506764
references.citation: Cancer Metastasis Rev. 2012 Dec;31(3-4):753-61
references.pmid: 22711031
references.citation: Expert Opin Ther Targets. 2005 Aug;9(4):825-30
references.pmid: 16083345
references.citation: Nat Genet. 2012 Mar 04;44(4):461-6
references.pmid: 22387997
references.citation: J Clin Oncol. 2012 Jan 20;30(3):256-62
references.pmid: 22184397
references.citation: Pediatr Blood Cancer. 2009 Mar;52(3):324-7
references.pmid: 18989890
references.citation: Med Pediatr Oncol. 2003 May;40(5):276-87
references.pmid: 12652615
references.citation: J Clin Oncol. 2011 Dec 1;29(34):4541-7
references.pmid: 22025149
references.citation: Cancer Res. 2002 Nov 1;62(21):6108-15
references.pmid: 12414635
references.citation: Nature. 1992 Sep 10;359(6391):162-5
references.pmid: 1522903
references.citation: N Engl J Med. 2003 Feb 20;348(8):694-701
references.pmid: 12594313
references.citation: Br J Cancer. 2001 May 18;84(10):1424-31
references.pmid: 11355958
references.citation: Pediatr Blood Cancer. 2010 Jul 1;54(7):921-6
references.pmid: 20166202
references.citation: Br J Cancer. 2012 Mar 13;106(6):1123-33
references.pmid: 22374462
references.citation: Cancer Res. 2008 Apr 1;68(7):2176-85
references.pmid: 18381423
references.citation: PLoS One. 2011 Apr 29;6(4):e19305
references.pmid: 21559395
references.citation: Int J Cancer. 2011 Jan 1;128(1):216-26
references.pmid: 20648560
references.citation: Clin Cancer Res. 2010 Apr 15;16(8):2363-74
references.pmid: 20371692
references.citation: PLoS One. 2008 Apr 16;3(4):e1965
references.pmid: 18414662
references.citation: J Natl Cancer Inst. 2011 Jun 22;103(12):962-78
references.pmid: 21653923
references.citation: Nat Med. 2009 Jul;15(7):750-6
references.pmid: 19584866
references.citation: Int J Cancer. 2012 Nov 1;131(9):2153-64
references.pmid: 22323082
references.citation: Nature. 2005 Aug 25;436(7054):1186-90
references.pmid: 15995699
references.citation: J Pediatr Hematol Oncol. 2008 Jun;30(6):425-30
references.pmid: 18525458
references.citation: Cell Cycle. 2008 Jan 15;7(2):250-6
references.pmid: 18256529
references.citation: Cancer Cell Int. 2008 Nov 17;8:16
references.pmid: 19014694
references.citation: Cancer Cell. 2006 May;9(5):405-16
references.pmid: 16697960
references.citation: Br J Cancer. 2013 Aug 6;109(3):658-66
references.pmid: 23839490
references.citation: J Clin Oncol. 2012 Nov 20;30(33):4148-54
references.pmid: 23091096
references.citation: J Clin Oncol. 2012 Nov 20;30(33):4141-7
references.pmid: 23071222
references.citation: Neoplasia. 2011 Feb;13(2):145-53
references.pmid: 21403840
references.citation: Br J Cancer. 2009 Jul 7;101(1):80-90
references.pmid: 19491900
references.citation: Cancer Biol Ther. 2012 Apr;13(6):417-24
references.pmid: 22313685
references.citation: Cancer Res. 1990 Jan 1;50(1):38-43
references.pmid: 2104538
references.citation: Sarcoma. 2011;2011:837474
references.pmid: 21197473
references.citation: Oncogene. 2013 Oct 17;32(42):5089-100
references.pmid: 23178492
references.citation: Mol Cancer Ther. 2010 May;9(5):1396-407
references.pmid: 20423994
references.citation: Nature. 2012 Mar 28;483(7391):570-5
references.pmid: 22460902
references.citation: Clin Cancer Res. 2012 May 1;18(9):2625-31
references.pmid: 22465830
references.citation: Cancer Res. 2006 Jun 1;66(11):5574-81
references.pmid: 16740692
references.citation: Oncotarget. 2012 Feb;3(2):172-82
references.pmid: 22383402
references.citation: Mol Immunol. 2008 Sep;45(15):3917-25
references.pmid: 18657862
references.citation: PLoS One. 2011 Apr 06;6(4):e18424
references.pmid: 21494688
references.citation: Cancer Genet. 2011 Jul;204(7):351-65
references.pmid: 21872822
references.citation: N Engl J Med. 2013 Apr 18;368(16):1509-1518
references.pmid: 23527958
references.citation: N Engl J Med. 2013 Jul 11;369(2):134-44
references.pmid: 23724846
references.citation: Eur J Cancer. 2012 Mar;48(4):579-85
references.pmid: 22088484
references.citation: J Clin Oncol. 2008 Sep 20;26(27):4385-93
references.pmid: 18802150
references.citation: Clin Sarcoma Res. 2012 Feb 08;2(1):8
references.pmid: 22587892