Systemic Treatment of Ewing Sarcoma: Current Options and Future Perspectives

[1] Bellan DG, Filho RJ, Garcia JG, de Toledo Petrilli M, Maia Viola DC, Schoedl MF, Petrilli AS. Ewing's sarcoma: Epidemiology and prognosis for patients treated at the Pediatric Oncology Institute, IOP-GRAACC-UNIFESP. Rev Bras Ortop. 2015 Dec 8;47(4):446–450. doi:10.1016/S2255-4971(15)30126-9. PMID: 27047848; PMCID: PMC4799471. BellanDG FilhoRJ GarciaJG de Toledo PetrilliM Maia ViolaDC SchoedlMF PetrilliAS Ewing's sarcoma: Epidemiology and prognosis for patients treated at the Pediatric Oncology Institute, IOP-GRAACC-UNIFESP Rev Bras Ortop 2015 Dec 8 47 4 446 450 10.1016/S2255-4971(15)30126-9 PMID: 27047848; PMCID: PMC4799471. 479947127047848 Open DOISearch in Google Scholar

[2] Franchi A. Epidemiology and classification of bone tumors. Clin Cases Miner Bone Metab. 2012 May;9(2):92–95. Epub 2012 Sep 30. PMID: 23087718; PMCID: PMC3476517. FranchiA Epidemiology and classification of bone tumors Clin Cases Miner Bone Metab 2012 May 9 2 92 95 Epub 2012 Sep 30. PMID: 23087718; PMCID: PMC3476517. Search in Google Scholar

[3] Bernstein M, Kovar H, Paulussen M, Randall RL, Schuck A, Teot LA, Juergens H. Ewing's sarcoma family of tumors: Current management. Oncologist. 2006 May;11(5):503–519. doi:10.1634/theoncologist.11-5-503. PMID: 16720851. BernsteinM KovarH PaulussenM RandallRL SchuckA TeotLA JuergensH Ewing's sarcoma family of tumors: Current management Oncologist 2006 May 11 5 503 519 10.1634/theoncologist.11-5-503 PMID: 16720851. 16720851 Open DOISearch in Google Scholar

[4] Jedlicka P. Ewing sarcoma, an enigmatic malignancy of likely progenitor cell origin, driven by transcription factor oncogenic fusions. Int J Clin Exp Pathol. 2010 Mar 19;3(4):338–347. PMID: 20490326; PMCID: PMC2872742. JedlickaP Ewing sarcoma, an enigmatic malignancy of likely progenitor cell origin, driven by transcription factor oncogenic fusions Int J Clin Exp Pathol 2010 Mar 19 3 4 338 347 PMID: 20490326; PMCID: PMC2872742. Search in Google Scholar

[5] Miser JS, Goldsby RE, Chen Z, Krailo MD, Tarbell NJ, Link MP, et al. Treatment of metastatic Ewing sarcoma/primitive neuroectodermal tumor of bone: Evaluation of increasing the dose intensity of chemotherapy—A report from the Children's Oncology Group. Pediatr Blood Cancer. 2007 Dec;49(7):894–900. doi:10.1002/pbc.21233. PMID: 17584910. MiserJS GoldsbyRE ChenZ KrailoMD TarbellNJ LinkMP Treatment of metastatic Ewing sarcoma/primitive neuroectodermal tumor of bone: Evaluation of increasing the dose intensity of chemotherapy—A report from the Children's Oncology Group Pediatr Blood Cancer 2007 Dec 49 7 894 900 10.1002/pbc.21233 PMID: 17584910. 17584910 Open DOISearch in Google Scholar

[6] Casali PG, Bielack S, Abecassis N, Aro HT, Bauer S, Biagini R, et al. ESMO Guidelines Committee, PaedCan and ERN EURACAN. Bone sarcomas: ESMO-PaedCan-EURACAN clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1;29(Suppl. 4):iv79–iv95. doi:10.1093/annonc/mdy310. PMID: 30285218. CasaliPG BielackS AbecassisN AroHT BauerS BiaginiR ESMO Guidelines Committee, PaedCan and ERN EURACAN Bone sarcomas: ESMO-PaedCan-EURACAN clinical practice guidelines for diagnosis, treatment and follow-up Ann Oncol 2018 Oct 1 29 Suppl. 4 iv79 iv95 10.1093/annonc/mdy310 PMID: 30285218. 30285218 Open DOISearch in Google Scholar

[7] Bacci G, Boriani S, Balladelli A, Barbieri E, Longhi A, Alberghini M, et al. Treatment of nonmetastatic Ewing's sarcoma family tumors of the spine and sacrum: The experience from a single institution. Eur Spine J. 2009 Aug;18(8):1091–1095. doi:10.1007/s00586-009-0921-0. Epub 2009 Mar 11. PMID: 19277725; PMCID: PMC2899506. BacciG BorianiS BalladelliA BarbieriE LonghiA AlberghiniM Treatment of nonmetastatic Ewing's sarcoma family tumors of the spine and sacrum: The experience from a single institution Eur Spine J 2009 Aug 18 8 1091 1095 10.1007/s00586-009-0921-0 Epub 2009 Mar 11. PMID: 19277725; PMCID: PMC2899506. 289950619277725 Open DOISearch in Google Scholar

[8] Serlo J, Helenius I, Vettenranta K, Perkkiö M, Riikonen P, Sampo M, Tarkkanen M. Surgically treated patients with axial and peripheral Ewing's sarcoma family of tumours: A population based study in Finland during 1990–2009. Eur J Surg Oncol. 2015 Jul;41(7):893–898. doi:10.1016/j.ejso.2015.02.010. Epub 2015 Mar 19. PMID: 25817983. SerloJ HeleniusI VettenrantaK PerkkiöM RiikonenP SampoM TarkkanenM Surgically treated patients with axial and peripheral Ewing's sarcoma family of tumours: A population based study in Finland during 1990–2009 Eur J Surg Oncol 2015 Jul 41 7 893 898 10.1016/j.ejso.2015.02.010 Epub 2015 Mar 19. PMID: 25817983. 25817983 Open DOISearch in Google Scholar

[9] Rodríguez-Galindo C, Liu T, Krasin MJ, Wu J, Billups CA, Daw NC, et al. Analysis of prognostic factors in Ewing sarcoma family of tumors: Review of St. Jude Children's Research Hospital studies. Cancer. 2007 Jul 15;110(2):375–384. doi:10.1002/cncr.22821. PMID: 17569105. Rodríguez-GalindoC LiuT KrasinMJ WuJ BillupsCA DawNC Analysis of prognostic factors in Ewing sarcoma family of tumors: Review of St. Jude Children's Research Hospital studies Cancer 2007 Jul 15 110 2 375 384 10.1002/cncr.22821 PMID: 17569105. 17569105 Open DOISearch in Google Scholar

[10] Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM, et al. The Ewing family of tumors—A subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med. 1994 Aug 4;331(5):294–299. doi:10.1056/NEJM199408043310503. PMID: 8022439. DelattreO ZucmanJ MelotT GarauXS ZuckerJM LenoirGM The Ewing family of tumors—A subgroup of small-round-cell tumors defined by specific chimeric transcripts N Engl J Med 1994 Aug 4 331 5 294 299 10.1056/NEJM199408043310503 PMID: 8022439. 8022439 Open DOISearch in Google Scholar

[11] Denny CT. Gene rearrangements in Ewing's sarcoma. Cancer Invest. 1996;14(1):83–88. doi:10.3109/07357909609018438. PMID: 8597892. DennyCT Gene rearrangements in Ewing's sarcoma Cancer Invest 1996 14 1 83 88 10.3109/07357909609018438 PMID: 8597892. 8597892 Open DOISearch in Google Scholar

[12] Li S, Siegal GP. Small cell tumors of bone. Adv Anat Pathol. 2010 Jan;17(1):1–11. doi:10.1097/PAP.0b013e3181bb6b9c. PMID: 20032633. LiS SiegalGP Small cell tumors of bone Adv Anat Pathol 2010 Jan 17 1 1 11 10.1097/PAP.0b013e3181bb6b9c PMID: 20032633. 20032633 Open DOISearch in Google Scholar

[13] Ross KA, Smyth NA, Murawski CD, Kennedy JG. The biology of Ewing sarcoma. ISRN Oncol. 2013;2013:759725. doi:10.1155/2013/759725. Epub 2013 Jan 10. PMID: 23346417; PMCID: PMC3549336. RossKA SmythNA MurawskiCD KennedyJG The biology of Ewing sarcoma ISRN Oncol 2013 2013 759725. 10.1155/2013/759725 Epub 2013 Jan 10. PMID: 23346417; PMCID: PMC3549336. 354933623346417 Open DOISearch in Google Scholar

[14] Tirode F, Laud-Duval K, Prieur A, Delorme B, Charbord P, Delattre O. Mesenchymal stem cell features of Ewing tumors. Cancer Cell. 2007 May;11(5):421–429. doi:10.1016/j.ccr.2007.02.027. PMID: 17482132. TirodeF Laud-DuvalK PrieurA DelormeB CharbordP DelattreO Mesenchymal stem cell features of Ewing tumors Cancer Cell 2007 May 11 5 421 429 10.1016/j.ccr.2007.02.027 PMID: 17482132. 17482132 Open DOISearch in Google Scholar

[15] Toomey EC, Schiffman JD, Lessnick SL. Recent advances in the molecular pathogenesis of Ewing's sarcoma. Oncogene. 2010 Aug 12;29(32):4504–4516. doi:10.1038/onc.2010.205. Epub 2010 Jun 14. PMID: 20543858; PMCID: PMC3555143. ToomeyEC SchiffmanJD LessnickSL Recent advances in the molecular pathogenesis of Ewing's sarcoma Oncogene 2010 Aug 12 29 32 4504 4516 10.1038/onc.2010.205 Epub 2010 Jun 14. PMID: 20543858; PMCID: PMC3555143. 355514320543858 Open DOISearch in Google Scholar

[16] Grünewald TG, Bernard V, Gilardi-Hebenstreit P, Raynal V, Surdez D, Aynaud MM, et al. Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite. Nat Genet. 2015 Sep;47(9):1073–1078. doi:10.1038/ng.3363. Epub 2015 Jul 27. PMID: 26214589; PMCID: PMC4591073. GrünewaldTG BernardV Gilardi-HebenstreitP RaynalV SurdezD AynaudMM Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite Nat Genet 2015 Sep 47 9 1073 1078 10.1038/ng.3363 Epub 2015 Jul 27. PMID: 26214589; PMCID: PMC4591073. 459107326214589 Open DOISearch in Google Scholar

[17] J.A. Ludwig, N. Federman, P. Anderson, M.E. Macy, L.E. Davis, R.F. Riedel et al., Phase I study of TK216, a novel anti-ETS agent for Ewing sarcoma. Annals of Oncol. 2020;31(suppl_4):S914–S933. doi:10.1016/annonc/annonc288. LudwigJ.A. FedermanN. AndersonP. MacyM.E. DavisL.E. RiedelR.F. Phase I study of TK216, a novel anti-ETS agent for Ewing sarcoma Annals of Oncol 2020 31 suppl_4 S914 S933 10.1016/annonc/annonc288 Open DOISearch in Google Scholar

[18] Cidre-Aranaz F, Alonso J. EWS/FLI1 Target genes and therapeutic opportunities in Ewing sarcoma. Front Oncol. 2015 Jul 20;5:162. doi:10.3389/fonc.2015.00162. PMID: 26258070; PMCID: PMC4507460. Cidre-AranazF AlonsoJ EWS/FLI1 Target genes and therapeutic opportunities in Ewing sarcoma Front Oncol 2015 Jul 20 5 162 10.3389/fonc.2015.00162 PMID: 26258070; PMCID: PMC4507460. 450746026258070 Open DOISearch in Google Scholar

[19] Dunst J, Jürgens H, Sauer R, Pape H, Paulussen M, Winkelmann W, Rübe C. Radiation therapy in Ewing's sarcoma: An update of the CESS 86 trial. Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):919–930. doi:10.1016/0360-3016(95)00016-r. PMID: 7607966. DunstJ JürgensH SauerR PapeH PaulussenM WinkelmannW RübeC Radiation therapy in Ewing's sarcoma: An update of the CESS 86 trial Int J Radiat Oncol Biol Phys 1995 Jul 15 32 4 919 930 10.1016/0360-3016(95)00016-r PMID: 7607966. 7607966 Open DOISearch in Google Scholar

[20] Schuck A, Ahrens S, Paulussen M, Kuhlen M, Könemann S, Rübe C, et al. Local therapy in localized Ewing tumors: Results of 1058 patients treated in the CESS 81, CESS 86, and EICESS 92 trials. Int J Radiat Oncol Biol Phys. 2003 Jan 1;55(1):168–177. doi:10.1016/s0360-3016(02)03797-5. PMID: 12504050. SchuckA AhrensS PaulussenM KuhlenM KönemannS RübeC Local therapy in localized Ewing tumors: Results of 1058 patients treated in the CESS 81, CESS 86, and EICESS 92 trials Int J Radiat Oncol Biol Phys 2003 Jan 1 55 1 168 177 10.1016/s0360-3016(02)03797-5 PMID: 12504050. 12504050 Open DOISearch in Google Scholar

[21] Yock TI, Krailo M, Fryer CJ, Donaldson SS, Miser JS, Chen Z, et al. Children's Oncology Group. Local control in pelvic Ewing sarcoma: Analysis from INT-0091—A report from the Children's Oncology Group. J Clin Oncol. 2006 Aug 20;24(24):3838–3843. doi:10.1200/JCO.2006.05.9188. Erratum in: J Clin Oncol. 2006 Oct 20;24(30):4947. PMID: 16921035. YockTI KrailoM FryerCJ DonaldsonSS MiserJS ChenZ Children's Oncology Group Local control in pelvic Ewing sarcoma: Analysis from INT-0091—A report from the Children's Oncology Group J Clin Oncol 2006 Aug 20 24 24 3838 3843 10.1200/JCO.2006.05.9188 Erratum in: J Clin Oncol. 2006 Oct 20;24(30):4947. PMID: 16921035. 16921035 Open DOISearch in Google Scholar

[22] DuBois SG, Krailo MD, Gebhardt MC, Donaldson SS, Marcus KJ, Dormans J, et al. Comparative evaluation of local control strategies in localized Ewing sarcoma of bone: A report from the Children's Oncology Group. Cancer. 2015 Feb 1;121(3):467–475. doi:10.1002/cncr.29065. Epub 2014 Sep 23. PMID: 25251206; PMCID: PMC4305012. DuBoisSG KrailoMD GebhardtMC DonaldsonSS MarcusKJ DormansJ Comparative evaluation of local control strategies in localized Ewing sarcoma of bone: A report from the Children's Oncology Group Cancer 2015 Feb 1 121 3 467 475 10.1002/cncr.29065 Epub 2014 Sep 23. PMID: 25251206; PMCID: PMC4305012. 430501225251206 Open DOISearch in Google Scholar

[23] Schuck A, Ahrens S, von Schorlemer I, Kuhlen M, Paulussen M, Hunold A, et al. Radiotherapy in Ewing tumors of the vertebrae: Treatment results and local relapse analysis of the CESS 81/86 and EICESS 92 trials. Int J Radiat Oncol Biol Phys. 2005 Dec 1;63(5):1562–1567. doi:10.1016/j.ijrobp.2005.05.036. Epub 2005 Aug 30. PMID: 16137838. SchuckA AhrensS von SchorlemerI KuhlenM PaulussenM HunoldA Radiotherapy in Ewing tumors of the vertebrae: Treatment results and local relapse analysis of the CESS 81/86 and EICESS 92 trials Int J Radiat Oncol Biol Phys 2005 Dec 1 63 5 1562 1567 10.1016/j.ijrobp.2005.05.036 Epub 2005 Aug 30. PMID: 16137838. 16137838 Open DOISearch in Google Scholar

[24] Indelicato DJ, Keole SR, Shahlaee AH, Shi W, Morris CG, Marcus RB Jr. Definitive radiotherapy for Ewing tumors of extremities and pelvis: Long-term disease control, limb function, and treatment toxicity. Int J Radiat Oncol Biol Phys. 2008 Nov 1;72(3):871–877. doi:10.1016/j.ijrobp.2008.02.023. Epub 2008 May 1. PMID: 18455323. IndelicatoDJ KeoleSR ShahlaeeAH ShiW MorrisCG MarcusRBJr Definitive radiotherapy for Ewing tumors of extremities and pelvis: Long-term disease control, limb function, and treatment toxicity Int J Radiat Oncol Biol Phys 2008 Nov 1 72 3 871 877 10.1016/j.ijrobp.2008.02.023 Epub 2008 May 1. PMID: 18455323. 18455323 Open DOISearch in Google Scholar

[25] Nesbit ME Jr, Gehan EA, Burgert EO Jr, Vietti TJ, Cangir A, Tefft M, et al. Multimodal therapy for the management of primary, nonmetastatic Ewing's sarcoma of bone: A long-term follow-up of the First Intergroup study. J Clin Oncol. 1990 Oct;8(10):1664–1674. doi:10.1200/JCO.1990.8.10.1664. PMID: 2213103. NesbitMEJr GehanEA BurgertEOJr ViettiTJ CangirA TefftM Multimodal therapy for the management of primary, nonmetastatic Ewing's sarcoma of bone: A long-term follow-up of the First Intergroup study J Clin Oncol 1990 Oct 8 10 1664 1674 10.1200/JCO.1990.8.10.1664 PMID: 2213103. 2213103 Open DOISearch in Google Scholar

[26] Burgert EO Jr, Nesbit ME, Garnsey LA, Gehan EA, Herrmann J, Vietti TJ, et al. Multimodal therapy for the management of nonpelvic, localized Ewing's sarcoma of bone: Intergroup study IESS-II. J Clin Oncol. 1990 Sep;8(9):1514–1524. doi:10.1200/JCO.1990.8.9.1514. PMID: 2099751. BurgertEOJr NesbitME GarnseyLA GehanEA HerrmannJ ViettiTJ Multimodal therapy for the management of nonpelvic, localized Ewing's sarcoma of bone: Intergroup study IESS-II J Clin Oncol 1990 Sep 8 9 1514 1524 10.1200/JCO.1990.8.9.1514 PMID: 2099751. 2099751 Open DOISearch in Google Scholar

[27] Grier HE, Krailo MD, Tarbell NJ, Link MP, Fryer CJ, Pritchard DJ, et al. Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med. 2003 Feb 20;348(8):694–701. doi:10.1056/NEJMoa020890. PMID: 12594313. GrierHE KrailoMD TarbellNJ LinkMP FryerCJ PritchardDJ Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone N Engl J Med 2003 Feb 20 348 8 694 701 10.1056/NEJMoa020890 PMID: 12594313. 12594313 Open DOISearch in Google Scholar

[28] Granowetter L, Womer R, Devidas M, Krailo M, Wang C, Bernstein M, et al. Dose-intensified compared with standard chemotherapy for nonmetastatic Ewing sarcoma family of tumors: A Children's Oncology Group Study. J Clin Oncol. 2009 May 20;27(15):2536–2541. doi:10.1200/JCO.2008.19.1478. Epub 2009 Apr 6. PMID: 19349548; PMCID: PMC2684856. GranowetterL WomerR DevidasM KrailoM WangC BernsteinM Dose-intensified compared with standard chemotherapy for nonmetastatic Ewing sarcoma family of tumors: A Children's Oncology Group Study J Clin Oncol 2009 May 20 27 15 2536 2541 10.1200/JCO.2008.19.1478 Epub 2009 Apr 6. PMID: 19349548; PMCID: PMC2684856. 268485619349548 Open DOISearch in Google Scholar

[29] Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, et al. Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: A report from the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148–4154. doi:10.1200/JCO.2011.41.5703. Epub 2012 Oct 22. Erratum in: J Clin Oncol. 2015 Mar 1;33(7):814. Dosage error in article text. PMID: 23091096; PMCID: PMC3494838. WomerRB WestDC KrailoMD DickmanPS PawelBR GrierHE Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: A report from the Children's Oncology Group J Clin Oncol 2012 Nov 20 30 33 4148 4154 10.1200/JCO.2011.41.5703 Epub 2012 Oct 22. Erratum in: J Clin Oncol. 2015 Mar 1;33(7):814. Dosage error in article text. PMID: 23091096; PMCID: PMC3494838. 349483823091096 Open DOISearch in Google Scholar

[30] Paulussen M, Craft AW, Lewis I, Hackshaw A, Douglas C, Dunst J, et al. European Intergroup Cooperative Ewing's Sarcoma Study-92. Results of the EICESS-92 Study: Two randomized trials of Ewing's sarcoma treatment—Cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients. J Clin Oncol. 2008 Sep 20;26(27):4385–4393. doi:10.1200/JCO.2008.16.5720. PMID: 18802150. PaulussenM CraftAW LewisI HackshawA DouglasC DunstJ European Intergroup Cooperative Ewing's Sarcoma Study-92. Results of the EICESS-92 Study: Two randomized trials of Ewing's sarcoma treatment—Cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients J Clin Oncol 2008 Sep 20 26 27 4385 4393 10.1200/JCO.2008.16.5720 PMID: 18802150. 18802150 Open DOISearch in Google Scholar

[31] Le Deley MC, Paulussen M, Lewis I, Brennan B, Ranft A, Whelan J, et al. Cyclophosphamide compared with ifosfamide in consolidation treatment of standard-risk Ewing sarcoma: Results of the randomized noninferiority Euro-EWING99-R1 trial. J Clin Oncol. 2014 Aug 10;32(23):2440–2448. doi:10.1200/JCO.2013.54.4833. Epub 2014 Jun 30. PMID: 24982464. Le DeleyMC PaulussenM LewisI BrennanB RanftA WhelanJ Cyclophosphamide compared with ifosfamide in consolidation treatment of standard-risk Ewing sarcoma: Results of the randomized noninferiority Euro-EWING99-R1 trial J Clin Oncol 2014 Aug 10 32 23 2440 2448 10.1200/JCO.2013.54.4833 Epub 2014 Jun 30. PMID: 24982464. 24982464 Open DOISearch in Google Scholar

[32] Whelan J, Le Deley MC, Dirksen U, Le Teuff G, Brennan B, Gaspar N, et al. Euro-E.W.I.N.G.99 and EWING-2008 Investigators. High-dose chemotherapy and blood autologous stem-cell rescue compared with standard chemotherapy in localized high-risk Ewing sarcoma: Results of Euro-E.W.I.N.G.99 and Ewing-2008. J Clin Oncol. 2018 Sep 6;36(31):JCO2018782516. doi:10.1200/JCO.2018.78.2516. Epub ahead of print. PMID: 30188789; PMCID: PMC6209090. WhelanJ Le DeleyMC DirksenU Le TeuffG BrennanB GasparN Euro-E.W.I.N.G.99 and EWING-2008 Investigators. High-dose chemotherapy and blood autologous stem-cell rescue compared with standard chemotherapy in localized high-risk Ewing sarcoma: Results of Euro-E.W.I.N.G.99 and Ewing-2008 J Clin Oncol 2018 Sep 6 36 31 JCO2018782516. 10.1200/JCO.2018.78.2516 Epub ahead of print. PMID: 30188789; PMCID: PMC6209090. 620909030188789 Open DOISearch in Google Scholar

[33] https://clinicaltrials.gov/ https://clinicaltrials.gov/ Search in Google Scholar

[34] Ginsberg JP, Goodman P, Leisenring W, Ness KK, Meyers PA, Wolden SL, et al. Long-term survivors of childhood Ewing sarcoma: Report from the childhood cancer survivor study. J Natl Cancer Inst. 2010 Aug 18;102(16):1272–1283. doi:10.1093/jnci/djq278. Epub 2010 Jul 23. PMID: 20656964; PMCID: PMC2948841. GinsbergJP GoodmanP LeisenringW NessKK MeyersPA WoldenSL Long-term survivors of childhood Ewing sarcoma: Report from the childhood cancer survivor study J Natl Cancer Inst 2010 Aug 18 102 16 1272 1283 10.1093/jnci/djq278 Epub 2010 Jul 23. PMID: 20656964; PMCID: PMC2948841. 294884120656964 Open DOISearch in Google Scholar

[35] Eiser C. Assessment of health-related quality of life after bone cancer in young people: Easier said than done. Eur J Cancer. 2009 Jul;45(10):1744–1747. doi:10.1016/j.ejca.2009.02.025. Epub 2009 Mar 25. PMID: 19327986. EiserC Assessment of health-related quality of life after bone cancer in young people: Easier said than done Eur J Cancer 2009 Jul 45 10 1744 1747 10.1016/j.ejca.2009.02.025 Epub 2009 Mar 25. PMID: 19327986. 19327986 Open DOISearch in Google Scholar

[36] Hobusch GM, Lang N, Schuh R, Windhager R, Hofstaetter JG. Do patients with Ewing's sarcoma continue with sports activities after limb salvage surgery of the lower extremity? Clin Orthop Relat Res. 2015 Mar;473(3):839–846. doi:10.1007/s11999-014-3622-x. PMID: 24748070; PMCID: PMC4317429. HobuschGM LangN SchuhR WindhagerR HofstaetterJG Do patients with Ewing's sarcoma continue with sports activities after limb salvage surgery of the lower extremity? Clin Orthop Relat Res 2015 Mar 473 3 839 846 10.1007/s11999-014-3622-x PMID: 24748070; PMCID: PMC4317429. 431742924748070 Open DOISearch in Google Scholar

[37] Groundland JS, Ambler SB, Houskamp LD, Orriola JJ, Binitie OT, Letson GD. Surgical and functional outcomes after limb-preservation surgery for tumor in pediatric patients: A systematic review. JBJS Rev. 2016 Feb9;4(2):01874474-201602000-00002. doi:10.2106/JBJS.RVW.O.00013. PMID: 27490132. GroundlandJS AmblerSB HouskampLD OrriolaJJ BinitieOT LetsonGD Surgical and functional outcomes after limb-preservation surgery for tumor in pediatric patients: A systematic review JBJS Rev 2016 Feb 9 4 2 01874474-201602000-00002. 10.2106/JBJS.RVW.O.00013 PMID: 27490132. 27490132 Open DOISearch in Google Scholar

[38] Peccatori FA, Azim HA Jr, Orecchia R, Hoekstra HJ, Pavlidis N, Kesic V, Pentheroudakis G, ESMO Guidelines Working Group. Cancer, pregnancy and fertility: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct;24(Suppl 6):vi160–170. doi:10.1093/annonc/mdt199. Epub 2013 Jun 27. PMID: 23813932. PeccatoriFA AzimHAJr OrecchiaR HoekstraHJ PavlidisN KesicV PentheroudakisG ESMO Guidelines Working Group Cancer, pregnancy and fertility: ESMO clinical practice guidelines for diagnosis, treatment and follow-up Ann Oncol 2013 Oct 24 Suppl 6 vi160 170 10.1093/annonc/mdt199 Epub 2013 Jun 27. PMID: 23813932. 23813932 Open DOISearch in Google Scholar

[39] Romao RL, Lorenzo AJ. Fertility preservation options for children and adolescents with cancer. Can Urol Assoc J. 2017 Jan–Feb;11(1–2, Suppl 1):S97–S102. doi:10.5489/cuaj.4410. PMID: 28265333; PMCID: PMC5332250. RomaoRL LorenzoAJ Fertility preservation options for children and adolescents with cancer Can Urol Assoc J 2017 Jan–Feb 11 1–2, Suppl 1 S97 S102 10.5489/cuaj.4410 PMID: 28265333; PMCID: PMC5332250. 533225028265333 Open DOISearch in Google Scholar

[40] Chen H, Xiao L, Li J, Cui L, Huang W. Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in premenopausal women. Cochrane Database Syst Rev. 2019 Mar 3;3(3):CD008018. doi:10.1002/14651858.CD008018.pub3. PMID: 30827035; PMCID: PMC6397718. ChenH XiaoL LiJ CuiL HuangW Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in premenopausal women Cochrane Database Syst Rev 2019 Mar 3 3 3 CD008018. 10.1002/14651858.CD008018.pub3 PMID: 30827035; PMCID: PMC6397718. 639771830827035 Open DOISearch in Google Scholar

[41] Kyriazoglou A, Tsironis G, Liontos M, Papakosta A, Mahaira L, Thomakos N, et al., Ewing's sarcoma of the cervix: A case report of an unusual diagnosis in pregnancy treated with surgery, adjuvant VIDE and radiotherapy. Oncol Lett. 2019 Jun;17(6):5529–5535. doi:10.3892/ol.2019.10267. Epub 2019 Apr 18. PMID: 31186774; PMCID: PMC6507342. KyriazoglouA TsironisG LiontosM PapakostaA MahairaL ThomakosN Ewing's sarcoma of the cervix: A case report of an unusual diagnosis in pregnancy treated with surgery, adjuvant VIDE and radiotherapy Oncol Lett 2019 Jun 17 6 5529 5535 10.3892/ol.2019.10267 Epub 2019 Apr 18. PMID: 31186774; PMCID: PMC6507342. 650734231186774 Open DOISearch in Google Scholar

[42] Rodriguez-Galindo C, Billups CA, Kun LE, Rao BN, et al. Survival after recurrence of Ewing tumors: The St Jude Children's Research Hospital experience, 1979–1999. Cancer. 2002 Jan 15;94(2):561–569. doi:10.1002/cncr.10192. PMID: 11900241. Rodriguez-GalindoC BillupsCA KunLE RaoBN Survival after recurrence of Ewing tumors: The St Jude Children's Research Hospital experience, 1979–1999 Cancer 2002 Jan 15 94 2 561 569 10.1002/cncr.10192 PMID: 11900241. 11900241 Open DOISearch in Google Scholar

[43] Bacci G, Ferrari S, Longhi A, Donati D, De Paolis M, Forni C, et al. Therapy and survival after recurrence of Ewing's tumors: The Rizzoli experience in 195 patients treated with adjuvant and neoadjuvant chemotherapy from 1979 to 1997. Ann Oncol. 2003 Nov;14(11):1654–1659. doi:10.1093/annonc/mdg457. PMID: 14581274. BacciG FerrariS LonghiA DonatiD De PaolisM ForniC Therapy and survival after recurrence of Ewing's tumors: The Rizzoli experience in 195 patients treated with adjuvant and neoadjuvant chemotherapy from 1979 to 1997 Ann Oncol 2003 Nov 14 11 1654 1659 10.1093/annonc/mdg457 PMID: 14581274. 14581274 Open DOISearch in Google Scholar

[44] Robinson SI, Ahmed SK, Okuno SH, Arndt CA, Rose PS, Laack NN. Clinical outcomes of adult patients with relapsed Ewing sarcoma: A 30-year single-institution experience. Am J Clin Oncol. 2014 Dec;37(6):585–591. doi:10.1097/COC.0b013e318281d6ab. PMID: 23466580. RobinsonSI AhmedSK OkunoSH ArndtCA RosePS LaackNN Clinical outcomes of adult patients with relapsed Ewing sarcoma: A 30-year single-institution experience Am J Clin Oncol 2014 Dec 37 6 585 591 10.1097/COC.0b013e318281d6ab PMID: 23466580. 23466580 Open DOISearch in Google Scholar

[45] Navid F, Billups C, Liu T, Krasin MJ, Rodriguez-Galindo C. Second cancers in patients with the Ewing sarcoma family of tumours. Eur J Cancer. 2008 May;44(7):983–991. doi:10.1016/j.ejca.2008.02.027. Epub 2008 Mar 18. PMID: 18353632; PMCID: PMC2423466. NavidF BillupsC LiuT KrasinMJ Rodriguez-GalindoC Second cancers in patients with the Ewing sarcoma family of tumours Eur J Cancer 2008 May 44 7 983 991 10.1016/j.ejca.2008.02.027 Epub 2008 Mar 18. PMID: 18353632; PMCID: PMC2423466. 242346618353632 Open DOISearch in Google Scholar

[46] Rodriguez-Galindo C, Poquette CA, Marina NM, Head DR, Cain A, et al. Hematologic abnormalities and acute myeloid leukemia in children and adolescents administered intensified chemotherapy for the Ewing sarcoma family of tumors. J Pediatr Hematol Oncol. 2000 Jul–Aug;22(4):321–329. doi:10.1097/00043426-200007000-00008. PMID: 10959902. Rodriguez-GalindoC PoquetteCA MarinaNM HeadDR CainA Hematologic abnormalities and acute myeloid leukemia in children and adolescents administered intensified chemotherapy for the Ewing sarcoma family of tumors J Pediatr Hematol Oncol 2000 Jul–Aug 22 4 321 329 10.1097/00043426-200007000-00008 PMID: 10959902. 10959902 Open DOISearch in Google Scholar

[47] Anderson P, Kopp L, Anderson N, Cornelius K, Herzog C, Hughes D, Huh W. Novel bone cancer drugs: Investigational agents and control paradigms for primary bone sarcomas (Ewing's sarcoma and osteosarcoma). Expert Opin Investig Drugs. 2008 Nov;17(11):1703–1715. doi:10.1517/13543784.17.11.1703. PMID: 18922107. AndersonP KoppL AndersonN CorneliusK HerzogC HughesD HuhW Novel bone cancer drugs: Investigational agents and control paradigms for primary bone sarcomas (Ewing's sarcoma and osteosarcoma) Expert Opin Investig Drugs 2008 Nov 17 11 1703 1715 10.1517/13543784.17.11.1703 PMID: 18922107. 18922107 Open DOISearch in Google Scholar

[48] Wagner LM, McAllister N, Goldsby RE, Rausen AR, McNall-Knapp RY, McCarville MB, Albritton K. Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma. Pediatr Blood Cancer. 2007 Feb;48(2):132–139. doi:10.1002/pbc.20697. PMID: 16317751. WagnerLM McAllisterN GoldsbyRE RausenAR McNall-KnappRY McCarvilleMB AlbrittonK Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma Pediatr Blood Cancer 2007 Feb 48 2 132 139 10.1002/pbc.20697 PMID: 16317751. 16317751 Open DOISearch in Google Scholar

[49] Raciborska A, Bilska K, Drabko K, Chaber R, Pogorzala M, Wyrobek E, et al. Vincristine, irinotecan, and temozolomide in patients with relapsed and refractory Ewing sarcoma. Pediatr Blood Cancer. 2013 Oct;60(10):1621–1625. doi:10.1002/pbc.24621. Epub 2013 Jun 15. PMID: 23776128. RaciborskaA BilskaK DrabkoK ChaberR PogorzalaM WyrobekE Vincristine, irinotecan, and temozolomide in patients with relapsed and refractory Ewing sarcoma Pediatr Blood Cancer 2013 Oct 60 10 1621 1625 10.1002/pbc.24621 Epub 2013 Jun 15. PMID: 23776128. 23776128 Open DOISearch in Google Scholar

[50] Casey DA, Wexler LH, Merchant MS, Chou AJ, Merola PR, Price AP, Meyers PA. Irinotecan and temozolomide for Ewing sarcoma: The Memorial Sloan-Kettering experience. Pediatr Blood Cancer. 2009 Dec;53(6):1029–1034. doi:10.1002/pbc.22206. PMID: 19637327. CaseyDA WexlerLH MerchantMS ChouAJ MerolaPR PriceAP MeyersPA Irinotecan and temozolomide for Ewing sarcoma: The Memorial Sloan-Kettering experience Pediatr Blood Cancer 2009 Dec 53 6 1029 1034 10.1002/pbc.22206 PMID: 19637327. 19637327 Open DOISearch in Google Scholar

[51] Palmerini E, Jones RL, Setola E, Picci P, Marchesi E, Luksch R, et al. Irinotecan and temozolomide in recurrent Ewing sarcoma: An analysis in 51 adult and pediatric patients. Acta Oncol. 2018 Jul;57(7):958–964. doi:10.1080/0284186X.2018.1449250. Epub 2018 Mar 13. PMID: 29533113. PalmeriniE JonesRL SetolaE PicciP MarchesiE LukschR Irinotecan and temozolomide in recurrent Ewing sarcoma: An analysis in 51 adult and pediatric patients Acta Oncol 2018 Jul 57 7 958 964 10.1080/0284186X.2018.1449250 Epub 2018 Mar 13. PMID: 29533113. 29533113 Open DOISearch in Google Scholar

[52] Büyükkapu Bay S, Kebudi R, Görgün O, Zülfikar B, Darendeliler E, Çakır FB. Vincristine, irinotecan, and temozolomide treatment for refractory/relapsed pediatric solid tumors: A single center experience. J Oncol Pharm Pract. 2019 Sep;25(6):1343–1348. doi:10.1177/1078155218790798. Epub 2018 Aug 6. PMID: 30080131. Büyükkapu BayS KebudiR GörgünO ZülfikarB DarendelilerE ÇakırFB Vincristine, irinotecan, and temozolomide treatment for refractory/relapsed pediatric solid tumors: A single center experience J Oncol Pharm Pract 2019 Sep 25 6 1343 1348 10.1177/1078155218790798 Epub 2018 Aug 6. PMID: 30080131. 30080131 Open DOISearch in Google Scholar

[53] Kurucu N, Sari N, Ilhan IE. Irinotecan and temozolamide treatment for relapsed Ewing sarcoma: A single-center experience and review of the literature. Pediatr Hematol Oncol. 2015 Feb;32(1):50–59. doi:10.3109/08880018.2014.954070. Epub 2014 Sep 24. PMID: 25252096. KurucuN SariN IlhanIE Irinotecan and temozolamide treatment for relapsed Ewing sarcoma: A single-center experience and review of the literature Pediatr Hematol Oncol 2015 Feb 32 1 50 59 10.3109/08880018.2014.954070 Epub 2014 Sep 24. PMID: 25252096. 25252096 Open DOISearch in Google Scholar

[54] Wagner LM, Perentesis JP, Reid JM, Ames MM, Safgren SL, Nelson MD Jr, Ingle AM, Blaney SM, Adamson PC. Phase I trial of two schedules of vincristine, oral irinotecan, and temozolomide (VOIT) for children with relapsed or refractory solid tumors: A Children's Oncology Group phase I consortium study. Pediatr Blood Cancer. 2010 Apr;54(4):538–545. doi:10.1002/pbc.22407. PMID: 20049936; PMCID: PMC3074342. WagnerLM PerentesisJP ReidJM AmesMM SafgrenSL NelsonMDJr IngleAM BlaneySM AdamsonPC Phase I trial of two schedules of vincristine, oral irinotecan, and temozolomide (VOIT) for children with relapsed or refractory solid tumors: A Children's Oncology Group phase I consortium study Pediatr Blood Cancer 2010 Apr 54 4 538 545 10.1002/pbc.22407 PMID: 20049936; PMCID: PMC3074342. 307434220049936 Open DOISearch in Google Scholar

[55] Wagner LM. Fifteen years of irinotecan therapy for pediatric sarcoma: Where to next? Clin Sarcoma Res. 2015 Aug 28;5:20. doi:10.1186/s13569-015-0035-x. PMID: 26322224; PMCID: PMC4552408. WagnerLM Fifteen years of irinotecan therapy for pediatric sarcoma: Where to next? Clin Sarcoma Res 2015 Aug 28 5 20 10.1186/s13569-015-0035-x PMID: 26322224; PMCID: PMC4552408. 455240826322224 Open DOISearch in Google Scholar

[56] Wagner LM, Crews KR, Iacono LC, Houghton PJ, Fuller CE, McCarville MB, et al. Phase I trial of temozolomide and protracted irinotecan in pediatric patients with refractory solid tumors. Clin Cancer Res. 2004 Feb 1;10(3):840–848. doi:10.1158/1078-0432.ccr-03-0175. PMID: 14871959. WagnerLM CrewsKR IaconoLC HoughtonPJ FullerCE McCarvilleMB Phase I trial of temozolomide and protracted irinotecan in pediatric patients with refractory solid tumors Clin Cancer Res 2004 Feb 1 10 3 840 848 10.1158/1078-0432.ccr-03-0175 PMID: 14871959. 14871959 Open DOISearch in Google Scholar

[57] Rapkin L, Qayed M, Brill P, Martin M, Clark D, George BA, et al. Gemcitabine and docetaxel (GEMDOX) for the treatment of relapsed and refractory pediatric sarcomas. Pediatr Blood Cancer. 2012 Nov;59(5):854–58. doi:10.1002/pbc.24101. Epub 2012 Feb 2. PMID: 22302783. RapkinL QayedM BrillP MartinM ClarkD GeorgeBA Gemcitabine and docetaxel (GEMDOX) for the treatment of relapsed and refractory pediatric sarcomas Pediatr Blood Cancer 2012 Nov 59 5 854 58 10.1002/pbc.24101 Epub 2012 Feb 2. PMID: 22302783. 22302783 Open DOISearch in Google Scholar

[58] Navid F, Willert JR, McCarville MB, Furman W, Watkins A, Roberts W, Daw NC. Combination of gemcitabine and docetaxel in the treatment of children and young adults with refractory bone sarcoma. Cancer. 2008 Jul 15;113(2):419–425. doi:10.1002/cncr.23586. PMID: 18484657. NavidF WillertJR McCarvilleMB FurmanW WatkinsA RobertsW DawNC Combination of gemcitabine and docetaxel in the treatment of children and young adults with refractory bone sarcoma Cancer 2008 Jul 15 113 2 419 425 10.1002/cncr.23586 PMID: 18484657. 18484657 Open DOISearch in Google Scholar

[59] Mora J, Cruz CO, Parareda A, de Torres C. Treatment of relapsed/refractory pediatric sarcomas with gemcitabine and docetaxel. J Pediatr Hematol Oncol. 2009 Oct;31(10):723–729. doi:10.1097/MPH.0b013e3181b2598c. PMID: 19727011. MoraJ CruzCO PararedaA de TorresC Treatment of relapsed/refractory pediatric sarcomas with gemcitabine and docetaxel J Pediatr Hematol Oncol 2009 Oct 31 10 723 729 10.1097/MPH.0b013e3181b2598c PMID: 19727011. 19727011 Open DOISearch in Google Scholar

[60] Van Winkle P, Angiolillo A, Krailo M, Cheung YK, Anderson B, Davenport V, et al. Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: The Children's Cancer Group (CCG) experience. Pediatr Blood Cancer. 2005 Apr;44(4):338–347. doi:10.1002/pbc.20227. PMID: 15503297. Van WinkleP AngiolilloA KrailoM CheungYK AndersonB DavenportV Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: The Children's Cancer Group (CCG) experience Pediatr Blood Cancer 2005 Apr 44 4 338 347 10.1002/pbc.20227 PMID: 15503297. 15503297 Open DOISearch in Google Scholar

[61] Miser JS, Kinsella TJ, Triche TJ, Tsokos M, Jarosinski P, Forquer R, et al. Ifosfamide with mesna uroprotection and etoposide: An effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. J Clin Oncol. 1987 Aug;5(8):1191–1198. doi:10.1200/JCO.1987.5.8.1191. PMID: 3114435. MiserJS KinsellaTJ TricheTJ TsokosM JarosinskiP ForquerR Ifosfamide with mesna uroprotection and etoposide: An effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults J Clin Oncol 1987 Aug 5 8 1191 1198 10.1200/JCO.1987.5.8.1191 PMID: 3114435. 3114435 Open DOISearch in Google Scholar

[62] Nardo M, Zambrano EM, Vicentini MF, Toloi D, Camargo VP, Feher O, Munhoz R. 5294—Efficacy of second line treatment with etoposide and ifosfamide in adult patients with advanced Ewing sarcoma family tumors. Annals of Oncol. 2017;28 (Suppl_5):v521–v538. doi:10.1093/annonc/mdx387. NardoM ZambranoEM VicentiniMF ToloiD CamargoVP FeherO MunhozR 5294—Efficacy of second line treatment with etoposide and ifosfamide in adult patients with advanced Ewing sarcoma family tumors Annals of Oncol 2017 28 Suppl_5 v521 v538 10.1093/annonc/mdx387 Open DOISearch in Google Scholar

[63] Kung FH, Pratt CB, Vega RA, Jaffe N, Strother D, Schwenn M, et al. Ifosfamide/etoposide combination in the treatment of recurrent malignant solid tumors of childhood. A Pediatric Oncology Group Phase II study. Cancer. 1993 Mar 1;71(5):1898–1903. doi:10.1002/1097-0142(19930301)71:5<1898::aidcncr2820710529>3.0.co;2-q. PMID: 8448755. KungFH PrattCB VegaRA JaffeN StrotherD SchwennM Ifosfamide/etoposide combination in the treatment of recurrent malignant solid tumors of childhood. A Pediatric Oncology Group Phase II study Cancer 1993 Mar 1 71 5 1898 1903 10.1002/1097-0142(19930301)71:5<1898::aidcncr2820710529>3.0.co;2-q PMID: 8448755. Open DOISearch in Google Scholar

[64] Hunold A, Weddeling N, Paulussen M, Ranft A, Liebscher C, Jürgens H. Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing tumors. Pediatr Blood Cancer. 2006 Nov;47(6):795–800. doi:10.1002/pbc.20719. PMID: 16411206. HunoldA WeddelingN PaulussenM RanftA LiebscherC JürgensH Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing tumors Pediatr Blood Cancer 2006 Nov 47 6 795 800 10.1002/pbc.20719 PMID: 16411206. 16411206 Open DOISearch in Google Scholar

[65] Saylors RL III, Stine KC, Sullivan J, Kepner JL, Wall DA, Bernstein ML, et al., Pediatric Oncology Group. Cyclophosphamide plus topotecan in children with recurrent or refractory solid tumors: A Pediatric Oncology Group phase II study. J Clin Oncol. 2001 Aug 1;19(15):3463–3469. doi:10.1200/JCO.2001.19.15.3463. PMID: 11481351. SaylorsRLIII StineKC SullivanJ KepnerJL WallDA BernsteinML Pediatric Oncology Group Cyclophosphamide plus topotecan in children with recurrent or refractory solid tumors: A Pediatric Oncology Group phase II study J Clin Oncol 2001 Aug 1 19 15 3463 3469 10.1200/JCO.2001.19.15.3463 PMID: 11481351. 11481351 Open DOISearch in Google Scholar

[66] Farhat R, Raad R, Khoury NJ, Feghaly J, Eid T, Muwakkit S, et al. Cyclophosphamide and topotecan as first-line salvage therapy in patients with relapsed Ewing sarcoma at a single institution. J Pediatr Hematol Oncol. 2013 Jul;35(5):356–360. doi:10.1097/MPH.0b013e318270a343. PMID: 23042020. FarhatR RaadR KhouryNJ FeghalyJ EidT MuwakkitS Cyclophosphamide and topotecan as first-line salvage therapy in patients with relapsed Ewing sarcoma at a single institution J Pediatr Hematol Oncol 2013 Jul 35 5 356 360 10.1097/MPH.0b013e318270a343 PMID: 23042020. 23042020 Open DOISearch in Google Scholar

[67] Bernstein ML, Devidas M, Lafreniere D, Souid AK, Meyers PA, Gebhardt M, et al. Pediatric Oncology Group; Children's Cancer Group Phase II Study 9457; Children's Oncology Group. Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457—A report from the Children's Oncology Group. J Clin Oncol. 2006 Jan 1;24(1):152–159. doi:10.1200/JCO.2005.02.1717. PMID: 16382125. BernsteinML DevidasM LafreniereD SouidAK MeyersPA GebhardtM Pediatric Oncology Group Children's Cancer Group Phase II Study 9457 Children's Oncology Group Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457—A report from the Children's Oncology Group J Clin Oncol 2006 Jan 1 24 1 152 159 10.1200/JCO.2005.02.1717 PMID: 16382125. 16382125 Open DOISearch in Google Scholar

[68] Kebudi R, Cakir FB, Gorgun O, Agaoglu FY, Darendeliler E. A modified protocol with vincristine, topotecan, and cyclophosphamide for recurrent/progressive Ewing sarcoma family tumors. Pediatr Hematol Oncol. 2013 Apr;30(3):170–77. doi:10.3109/08880018.2013.767868. PMID: 23484903. KebudiR CakirFB GorgunO AgaogluFY DarendelilerE A modified protocol with vincristine, topotecan, and cyclophosphamide for recurrent/progressive Ewing sarcoma family tumors Pediatr Hematol Oncol 2013 Apr 30 3 170 77 10.3109/08880018.2013.767868 PMID: 23484903. 23484903 Open DOISearch in Google Scholar

[69] Magnan H, Goodbody CM, Riedel E, Pratilas CA, Wexler LH, Chou AJ. Ifosfamide dose-intensification for patients with metastatic Ewing sarcoma. Pediatr Blood Cancer. 2015 Apr;62(4):594–597. doi:10.1002/pbc.25373. Epub 2015 Jan 28. PMID: 25630954; PMCID: PMC4474186. MagnanH GoodbodyCM RiedelE PratilasCA WexlerLH ChouAJ Ifosfamide dose-intensification for patients with metastatic Ewing sarcoma Pediatr Blood Cancer 2015 Apr 62 4 594 597 10.1002/pbc.25373 Epub 2015 Jan 28. PMID: 25630954; PMCID: PMC4474186. 447418625630954 Open DOISearch in Google Scholar

[70] Ferrari S, del Prever AB, Palmerini E, Staals E, Berta M, Balladelli A, et al. Response to high-dose ifosfamide in patients with advanced/recurrent Ewing sarcoma. Pediatr Blood Cancer. 2009 May;52(5):581–584. doi:10.1002/pbc.21917. PMID: 19142994. FerrariS del PreverAB PalmeriniE StaalsE BertaM BalladelliA Response to high-dose ifosfamide in patients with advanced/recurrent Ewing sarcoma Pediatr Blood Cancer 2009 May 52 5 581 584 10.1002/pbc.21917 PMID: 19142994. 19142994 Open DOISearch in Google Scholar

[71] Patel SR, Vadhan-Raj S, Papadopolous N, Plager C, Burgess MA, Hays C, Benjamin RS. High-dose ifosfamide in bone and soft tissue sarcomas: Results of phase II and pilot studies—Dose-response and schedule dependence. J Clin Oncol. 1997 Jun;15(6):2378–2384. doi:10.1200/JCO.1997.15.6.2378. PMID: 9196153. PatelSR Vadhan-RajS PapadopolousN PlagerC BurgessMA HaysC BenjaminRS High-dose ifosfamide in bone and soft tissue sarcomas: Results of phase II and pilot studies—Dose-response and schedule dependence J Clin Oncol 1997 Jun 15 6 2378 2384 10.1200/JCO.1997.15.6.2378 PMID: 9196153. 9196153 Open DOISearch in Google Scholar

[72] McCabe MG, Moroz V, Khan M, Dirksen U, Evans A, Fenwick N, et al., Euro Ewing Consortium. Results of the first interim assessment of rEECur, an international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma. J Clin Oncol. 2019 37(15_suppl):11007. McCabeMG MorozV KhanM DirksenU EvansA FenwickN Euro Ewing Consortium Results of the first interim assessment of rEECur, an international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma J Clin Oncol 2019 37 15_suppl 11007 10.1200/JCO.2019.37.15_suppl.11007 Search in Google Scholar

[73] McCabe MG, Kirton L, Khan M, Fenwick N, Dirksen U, Gaspar N, et al. Results of the second interim assessment of rEECur, an international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma (RR-ES). J Clin Oncol. 2020 38(15_suppl):11502. McCabeMG KirtonL KhanM FenwickN DirksenU GasparN Results of the second interim assessment of rEECur, an international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma (RR-ES) J Clin Oncol 2020 38 15_suppl 11502 10.1200/JCO.2020.38.15_suppl.11502 Search in Google Scholar

[74] McTiernan A, Driver D, Michelagnoli MP, Kilby AM, Whelan JS. High dose chemotherapy with bone marrow or peripheral stem cell rescue is an effective treatment option for patients with relapsed or progressive Ewing's sarcoma family of tumours. Ann Oncol. 2006 Aug;17(8):1301–1305. doi:10.1093/annonc/mdl108. Epub 2006 Jun 16. PMID: 16782749. McTiernanA DriverD MichelagnoliMP KilbyAM WhelanJS High dose chemotherapy with bone marrow or peripheral stem cell rescue is an effective treatment option for patients with relapsed or progressive Ewing's sarcoma family of tumours Ann Oncol 2006 Aug 17 8 1301 1305 10.1093/annonc/mdl108 Epub 2006 Jun 16. PMID: 16782749. 16782749 Open DOISearch in Google Scholar

[75] Al-Faris N, Al Harbi T, Goia C, Pappo A, Doyle J, Gassas A. Does consolidation with autologous stem cell transplantation improve the outcome of children with metastatic or relapsed Ewing sarcoma? Pediatr Blood Cancer. 2007 Aug;49(2):190–195. doi:10.1002/pbc.21140. PMID: 17262797. Al-FarisN Al HarbiT GoiaC PappoA DoyleJ GassasA Does consolidation with autologous stem cell transplantation improve the outcome of children with metastatic or relapsed Ewing sarcoma? Pediatr Blood Cancer 2007 Aug 49 2 190 195 10.1002/pbc.21140 PMID: 17262797. 17262797 Open DOISearch in Google Scholar

[76] Rasper M, Jabar S, Ranft A, Jürgens H, Amler S, Dirksen U. The value of high-dose chemotherapy in patients with first relapsed Ewing sarcoma. Pediatr Blood Cancer. 2014 Aug;61(8):1382–1386. doi:10.1002/pbc.25042. Epub 2014 Apr 11. PMID: 24729428. RasperM JabarS RanftA JürgensH AmlerS DirksenU The value of high-dose chemotherapy in patients with first relapsed Ewing sarcoma Pediatr Blood Cancer 2014 Aug 61 8 1382 1386 10.1002/pbc.25042 Epub 2014 Apr 11. PMID: 24729428. 24729428 Open DOISearch in Google Scholar

[77] Barker LM, Pendergrass TW, Sanders JE, Hawkins DS. Survival after recurrence of Ewing's sarcoma family of tumors. J Clin Oncol. 2005 Jul 1;23(19):4354–4362. doi:10.1200/JCO.2005.05.105. Epub 2005 Mar 21. PMID: 15781881. BarkerLM PendergrassTW SandersJE HawkinsDS Survival after recurrence of Ewing's sarcoma family of tumors J Clin Oncol 2005 Jul 1 23 19 4354 4362 10.1200/JCO.2005.05.105 Epub 2005 Mar 21. PMID: 15781881. 15781881 Open DOISearch in Google Scholar

[78] Koscielniak E, Gross-Wieltsch U, Treuner J, Winkler P, Klingebiel T, Lang P, et al. Graft-versus-Ewing sarcoma effect and long-term remission induced by haploidentical stem-cell transplantation in a patient with relapse of metastatic disease. J Clin Oncol. 2005 Jan 1;23(1):242–244. doi:10.1200/JCO.2005.05.940. PMID: 15625381. KoscielniakE Gross-WieltschU TreunerJ WinklerP KlingebielT LangP Graft-versus-Ewing sarcoma effect and long-term remission induced by haploidentical stem-cell transplantation in a patient with relapse of metastatic disease J Clin Oncol 2005 Jan 1 23 1 242 244 10.1200/JCO.2005.05.940 PMID: 15625381. 15625381 Open DOISearch in Google Scholar

[79] Demirer T, Barkholt L, Blaise D, Pedrazzoli P, Aglietta M, Carella AM, et al., EBMT Solid Tumors Working Party. Transplantation of allogeneic hematopoietic stem cells: An emerging treatment modality for solid tumors. Nat Clin Pract Oncol. 2008 May;5(5):256–67. doi:10.1038/ncponc1104. Epub 2008 Apr 8. PMID: 18398414. DemirerT BarkholtL BlaiseD PedrazzoliP AgliettaM CarellaAM EBMT Solid Tumors Working Party Transplantation of allogeneic hematopoietic stem cells: An emerging treatment modality for solid tumors Nat Clin Pract Oncol 2008 May 5 5 256 67 10.1038/ncponc1104 Epub 2008 Apr 8. PMID: 18398414. 18398414 Open DOISearch in Google Scholar

[80] Hale GA. Autologous hematopoietic stem cell transplantation for pediatric solid tumors. Expert Rev Anticancer Ther. 2005 Oct;5(5):835–846. doi:10.1586/14737140.5.5.835. PMID: 16221053. HaleGA Autologous hematopoietic stem cell transplantation for pediatric solid tumors Expert Rev Anticancer Ther 2005 Oct 5 5 835 846 10.1586/14737140.5.5.835 PMID: 16221053. 16221053 Open DOISearch in Google Scholar

[81] Kasper B, Lehnert T, Bernd L, Mechtersheimer G, Goldschmidt H, Ho AD, Egerer G. High-dose chemotherapy with autologous peripheral blood stem cell transplantation for bone and soft-tissue sarcomas. Bone Marrow Transplant. 2004 Jul;34(1):37–41. doi:10.1038/sj.bmt.1704520. PMID: 15170176. KasperB LehnertT BerndL MechtersheimerG GoldschmidtH HoAD EgererG High-dose chemotherapy with autologous peripheral blood stem cell transplantation for bone and soft-tissue sarcomas Bone Marrow Transplant 2004 Jul 34 1 37 41 10.1038/sj.bmt.1704520 PMID: 15170176. 15170176 Open DOISearch in Google Scholar

[82] Baird K, Fry TJ, Steinberg SM, Bishop MR, Fowler DH, Delbrook CP, et al. Reduced-intensity allogeneic stem cell transplantation in children and young adults with ultrahigh-risk pediatric sarcomas. Biol Blood Marrow Transplant. 2012 May;18(5):698–707. doi:10.1016/j.bbmt.2011.08.020. Epub 2011 Sep 5. PMID: 21896345; PMCID: PMC3262116. BairdK FryTJ SteinbergSM BishopMR FowlerDH DelbrookCP Reduced-intensity allogeneic stem cell transplantation in children and young adults with ultrahigh-risk pediatric sarcomas Biol Blood Marrow Transplant 2012 May 18 5 698 707 10.1016/j.bbmt.2011.08.020 Epub 2011 Sep 5. PMID: 21896345; PMCID: PMC3262116. 326211621896345 Open DOISearch in Google Scholar

[83] Drabko K, Raciborska A, Bilska K, Styczynski J, Ussowicz M, Choma M, et al. Consolidation of first-line therapy with busulphan and melphalan, and autologous stem cell rescue in children with Ewing's sarcoma. Bone Marrow Transplant. 2012 Dec;47(12):1530–1534. doi:10.1038/bmt.2012.78. Epub 2012 May 21. PMID: 22609883. DrabkoK RaciborskaA BilskaK StyczynskiJ UssowiczM ChomaM Consolidation of first-line therapy with busulphan and melphalan, and autologous stem cell rescue in children with Ewing's sarcoma Bone Marrow Transplant 2012 Dec 47 12 1530 1534 10.1038/bmt.2012.78 Epub 2012 May 21. PMID: 22609883. 22609883 Open DOISearch in Google Scholar

[84] Reed DR, Hayashi M, Wagner L, Binitie O, Steppan DA, Brohl AS, et al. Treatment pathway of bone sarcoma in children, adolescents, and young adults. Cancer. 2017 Jun 15;123(12):2206–2218. doi:10.1002/cncr.30589. Epub 2017 Mar 21. PMID: 28323337; PMCID: PMC5485018. ReedDR HayashiM WagnerL BinitieO SteppanDA BrohlAS Treatment pathway of bone sarcoma in children, adolescents, and young adults Cancer 2017 Jun 15 123 12 2206 2218 10.1002/cncr.30589 Epub 2017 Mar 21. PMID: 28323337; PMCID: PMC5485018. 548501828323337 Open DOISearch in Google Scholar

[85] Leemann-Zakaryan RP, Pahlich S, Sedda MJ, Quero L, Grossenbacher D, Gehring H. Dynamic subcellular localization of the Ewing sarcoma proto-oncoprotein and its association with and stabilization of microtubules. J Mol Biol. 2009 Feb 13;386(1):1–13. doi:10.1016/j.jmb.2008.12.039. Epub 2008 Dec 24. PMID: 19133275. Leemann-ZakaryanRP PahlichS SeddaMJ QueroL GrossenbacherD GehringH Dynamic subcellular localization of the Ewing sarcoma proto-oncoprotein and its association with and stabilization of microtubules J Mol Biol 2009 Feb 13 386 1 1 13 10.1016/j.jmb.2008.12.039 Epub 2008 Dec 24. PMID: 19133275. 19133275 Open DOISearch in Google Scholar

[86] Kolb EA, Gorlick R, Reynolds CP, Kang MH, Carol H, Lock R, et al. Initial testing (stage 1) of eribulin, a novel tubulin binding agent, by the pediatric preclinical testing program. Pediatr Blood Cancer. 2013 Aug;60(8):1325–1332. doi:10.1002/pbc.24517. Epub 2013 Mar 28. PMID: 23553917; PMCID: PMC4263960. KolbEA GorlickR ReynoldsCP KangMH CarolH LockR Initial testing (stage 1) of eribulin, a novel tubulin binding agent, by the pediatric preclinical testing program Pediatr Blood Cancer 2013 Aug 60 8 1325 1332 10.1002/pbc.24517 Epub 2013 Mar 28. PMID: 23553917; PMCID: PMC4263960. 426396023553917 Open DOISearch in Google Scholar

[87] Wagner LM, Yin H, Eaves D, Currier M, Cripe TP. Preclinical evaluation of nanoparticle albumin-bound paclitaxel for treatment of pediatric bone sarcoma. Pediatr Blood Cancer. 2014 Nov;61(11):2096–2098. doi:10.1002/pbc.25062. Epub 2014 Apr 19. PMID: 24753077. WagnerLM YinH EavesD CurrierM CripeTP Preclinical evaluation of nanoparticle albumin-bound paclitaxel for treatment of pediatric bone sarcoma Pediatr Blood Cancer 2014 Nov 61 11 2096 2098 10.1002/pbc.25062 Epub 2014 Apr 19. PMID: 24753077. 24753077 Open DOISearch in Google Scholar

[88] Le Cesne A, Cresta S, Maki RG, Blay JY, Verweij J, Poveda A, et al. A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas. Eur J Cancer. 2012 Nov;48(16):3036–3044. doi:10.1016/j.ejca.2012.05.012. Epub 2012 Jun 29. PMID: 22749255. Le CesneA CrestaS MakiRG BlayJY VerweijJ PovedaA A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas Eur J Cancer 2012 Nov 48 16 3036 3044 10.1016/j.ejca.2012.05.012 Epub 2012 Jun 29. PMID: 22749255. 22749255 Open DOISearch in Google Scholar

[89] Baruchel S, Pappo A, Krailo M, Baker KS, Wu B, Villaluna D, et al. A phase 2 trial of trabectedin in children with recurrent rhabdomyosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft tissue sarcomas: A report from the Children's Oncology Group. Eur J Cancer. 2012 Mar;48(4):579–585. doi:10.1016/j.ejca.2011.09.027. Epub 2011 Nov 14. PMID: 22088484. BaruchelS PappoA KrailoM BakerKS WuB VillalunaD A phase 2 trial of trabectedin in children with recurrent rhabdomyosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft tissue sarcomas: A report from the Children's Oncology Group Eur J Cancer 2012 Mar 48 4 579 585 10.1016/j.ejca.2011.09.027 Epub 2011 Nov 14. PMID: 22088484. 22088484 Open DOISearch in Google Scholar

[90] Romano M, Frapolli R, Zangarini M, Bello E, Porcu L, Galmarini CM, et al. Comparison of in vitro and in vivo biological effects of trabectedin, lurbinectedin (PM01183) and Zalypsis® (PM00104). Int J Cancer. 2013 Nov;133(9):2024–2033. doi:10.1002/ijc.28213. Epub 2013 May 25. PMID: 23588839. RomanoM FrapolliR ZangariniM BelloE PorcuL GalmariniCM Comparison of in vitro and in vivo biological effects of trabectedin, lurbinectedin (PM01183) and Zalypsis® (PM00104) Int J Cancer 2013 Nov 133 9 2024 2033 10.1002/ijc.28213 Epub 2013 May 25. PMID: 23588839. 23588839 Open DOISearch in Google Scholar

[91] Subbiah V, Kumar Sankhala K, Ratan R, Sanz Garcia E, Boni V, Gil T, et al. Efficacy and safety of lurbinectedin (PM1183) in Ewing sarcoma: Final results from a phase 2 study. J Clin Oncol. 2018;36(15_suppl):11519. SubbiahV Kumar SankhalaK RatanR Sanz GarciaE BoniV GilT Efficacy and safety of lurbinectedin (PM1183) in Ewing sarcoma: Final results from a phase 2 study J Clin Oncol 2018 36 15_suppl 11519 10.1200/JCO.2018.36.15_suppl.11519 Search in Google Scholar

[92] Brenner JC, Feng FY, Han S, Patel S, Goyal SV, Bou-Maroun LM, et al. PARP-1 inhibition as a targeted strategy to treat Ewing's sarcoma. Cancer Res. 2012 Apr 1;72(7):1608–1613. doi:10.1158/0008-5472.CAN-11-3648. Epub 2012 Jan 27. PMID: 22287547; PMCID: PMC3319786. BrennerJC FengFY HanS PatelS GoyalSV Bou-MarounLM PARP-1 inhibition as a targeted strategy to treat Ewing's sarcoma Cancer Res 2012 Apr 1 72 7 1608 1613 10.1158/0008-5472.CAN-11-3648 Epub 2012 Jan 27. PMID: 22287547; PMCID: PMC3319786. 331978622287547 Open DOISearch in Google Scholar

[93] Garnett MJ, Edelman EJ, Heidorn SJ, Greenman CD, Dastur A, Lau KW, et al. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature. 2012 Mar 28;483(7391):570–575. doi:10.1038/nature11005. PMID: 22460902; PMCID: PMC3349233. GarnettMJ EdelmanEJ HeidornSJ GreenmanCD DasturA LauKW Systematic identification of genomic markers of drug sensitivity in cancer cells Nature 2012 Mar 28 483 7391 570 575 10.1038/nature11005 PMID: 22460902; PMCID: PMC3349233. 334923322460902 Open DOISearch in Google Scholar

[94] Choy E, Butrynski JE, Harmon DC, Morgan JA, George S, Wagner AJ, et al. Phase II study of olaparib in patients with refractory Ewing sarcoma following failure of standard chemotherapy. BMC Cancer. 2014 Nov 5;14:813. doi:10.1186/1471-2407-14-813. PMID: 25374341; PMCID: PMC4230717. ChoyE ButrynskiJE HarmonDC MorganJA GeorgeS WagnerAJ Phase II study of olaparib in patients with refractory Ewing sarcoma following failure of standard chemotherapy BMC Cancer 2014 Nov 5 14 813 10.1186/1471-2407-14-813 PMID: 25374341; PMCID: PMC4230717. 423071725374341 Open DOISearch in Google Scholar

[95] Vormoor B, Schlosser YT, Blair H, Sharma A, Wilkinson S, Newell DR, Curtin N. Sensitizing Ewing sarcoma to chemo- and radiotherapy by inhibition of the DNA-repair enzymes DNA protein kinase (DNA-PK) and poly-ADP-ribose polymerase (PARP) 1/2. Oncotarget. 2017 Sep 28;8(69):113418–113430. doi:10.18632/oncotarget.21300. PMID: 29371919; PMCID: PMC5768336. VormoorB SchlosserYT BlairH SharmaA WilkinsonS NewellDR CurtinN Sensitizing Ewing sarcoma to chemo- and radiotherapy by inhibition of the DNA-repair enzymes DNA protein kinase (DNA-PK) and poly-ADP-ribose polymerase (PARP) 1/2 Oncotarget 2017 Sep 28 8 69 113418 113430 10.18632/oncotarget.21300 PMID: 29371919; PMCID: PMC5768336. 576833629371919 Open DOISearch in Google Scholar

[96] Stewart E, Goshorn R, Bradley C, Griffiths LM, Benavente C, Twarog NR, et al. Targeting the DNA repair pathway in Ewing sarcoma. Cell Rep. 2014 Nov 6;9(3):829–841. doi:10.1016/j.celrep.2014.09.028. Epub 2014 Oct 23. PMID: 25437539; PMCID: PMC4386669. StewartE GoshornR BradleyC GriffithsLM BenaventeC TwarogNR Targeting the DNA repair pathway in Ewing sarcoma Cell Rep 2014 Nov 6 9 3 829 841 10.1016/j.celrep.2014.09.028 Epub 2014 Oct 23. PMID: 25437539; PMCID: PMC4386669. 438666925437539 Open DOISearch in Google Scholar

[97] Smith MA, Reynolds CP, Kang MH, Kolb EA, Gorlick R, Carol H, et al. Synergistic activity of PARP inhibition by talazoparib (BMN 673) with temozolomide in pediatric cancer models in the pediatric preclinical testing program. Clin Cancer Res. 2015 Feb 15;21(4):819–832. doi:10.1158/1078-0432.CCR-14-2572. Epub 2014 Dec 10. Erratum in: Clin Cancer Res. 2017 Feb 15;23 (4):1118–1119. PMID: 25500058; PMCID: PMC4587665. SmithMA ReynoldsCP KangMH KolbEA GorlickR CarolH Synergistic activity of PARP inhibition by talazoparib (BMN 673) with temozolomide in pediatric cancer models in the pediatric preclinical testing program Clin Cancer Res 2015 Feb 15 21 4 819 832 10.1158/1078-0432.CCR-14-2572 Epub 2014 Dec 10. Erratum in: Clin Cancer Res. 2017 Feb 15;23 (4):1118–1119. PMID: 25500058; PMCID: PMC4587665. 458766525500058 Open DOISearch in Google Scholar

[98] Wilcoxen KM, Brooks DG, Tiruchinapalli D, Anderson N, Donaldson R, McIver Nivens, et al. The PARP inhibitor niraparib demonstrates synergy with chemotherapy in treatment of patient derived Ewing's sarcoma tumorGraft models [abstract]. In Proceedings of the AACR-NCI-EORTC International Conference: Molecular targets and cancer therapeutics; 2013 Oct 19–23; Boston, MA: AACR; Mol Cancer Ther. 2013;12(11 Suppl):Abstract nr A258. WilcoxenKM BrooksDG TiruchinapalliD AndersonN DonaldsonR McIverNivens The PARP inhibitor niraparib demonstrates synergy with chemotherapy in treatment of patient derived Ewing's sarcoma tumorGraft models [abstract]. In Proceedings of the AACR-NCI-EORTC International Conference: Molecular targets and cancer therapeutics; 2013 Oct 19–23; Boston, MA: AACR Mol Cancer Ther 2013 12 11 Suppl Abstract nr A258. 10.1158/1535-7163.TARG-13-A258 Search in Google Scholar

[99] Gill SJ, Travers J, Pshenichnaya I, Kogera FA, Barthorpe S, Mironenko T, et al. Combinations of PARP inhibitors with temozolomide drive PARP1 trapping and apoptosis in Ewing's sarcoma. PLoS One. 2015 Oct 27;10(10):e0140988. doi:10.1371/journal.pone.0140988. PMID: 26505995; PMCID: PMC4624427. GillSJ TraversJ PshenichnayaI KogeraFA BarthorpeS MironenkoT Combinations of PARP inhibitors with temozolomide drive PARP1 trapping and apoptosis in Ewing's sarcoma PLoS One 2015 Oct 27 10 10 e0140988. 10.1371/journal.pone.0140988 PMID: 26505995; PMCID: PMC4624427. 462442726505995 Open DOISearch in Google Scholar

[100] Iniguez AB, Stolte B, Wang EJ, Conway AS, Alexe G, Dharia NV, et al. EWS/FLI confers tumor cell synthetic lethality to CDK12 inhibition in Ewing sarcoma. Cancer Cell. 2018 Feb 12;33(2):202–216.e6. doi:10.1016/j.ccell.2017.12.009. Epub 2018 Jan 18. PMID: 29358035; PMCID: PMC5846483. IniguezAB StolteB WangEJ ConwayAS AlexeG DhariaNV EWS/FLI confers tumor cell synthetic lethality to CDK12 inhibition in Ewing sarcoma Cancer Cell 2018 Feb 12 33 2 202 216 e6 10.1016/j.ccell.2017.12.009 Epub 2018 Jan 18. PMID: 29358035; PMCID: PMC5846483. 584648329358035 Open DOISearch in Google Scholar

[101] Tang F, Choy E, Tu C, Hornicek F, Duan Z. Therapeutic applications of histone deacetylase inhibitors in sarcoma. Cancer Treat Rev. 2017 Sep;59:33–45. doi:10.1016/j.ctrv.2017.06.006. Epub 2017 Jul 6. PMID: 28732326; PMCID: PMC5581728. TangF ChoyE TuC HornicekF DuanZ Therapeutic applications of histone deacetylase inhibitors in sarcoma Cancer Treat Rev 2017 Sep 59 33 45 10.1016/j.ctrv.2017.06.006 Epub 2017 Jul 6. PMID: 28732326; PMCID: PMC5581728. 558172828732326 Open DOISearch in Google Scholar

[102] Sampson ER, Amin V, Schwarz EM, O’Keefe RJ, Rosier RN. The histone deacetylase inhibitor vorinostat selectively sensitizes fibrosarcoma cells to chemotherapy. J Orthop Res. 2011 Apr;29(4):623–32. doi:10.1002/jor.21274. Epub 2010 Oct 18. PMID: 20957741. SampsonER AminV SchwarzEM O’KeefeRJ RosierRN The histone deacetylase inhibitor vorinostat selectively sensitizes fibrosarcoma cells to chemotherapy J Orthop Res 2011 Apr 29 4 623 32 10.1002/jor.21274 Epub 2010 Oct 18. PMID: 20957741. 20957741 Open DOISearch in Google Scholar

[103] Heinicke U, Kupka J, Fulda S. JNJ-26481585 primes rhabdomyosarcoma cells for chemotherapeutics by engaging the mitochondrial pathway of apoptosis. Oncotarget. 2015 Nov 10;6(35):37836–37851. doi:10.18632/oncotarget.6097. PMID: 26473375; PMCID: PMC4741969. HeinickeU KupkaJ FuldaS JNJ-26481585 primes rhabdomyosarcoma cells for chemotherapeutics by engaging the mitochondrial pathway of apoptosis Oncotarget 2015 Nov 10 6 35 37836 37851 10.18632/oncotarget.6097 PMID: 26473375; PMCID: PMC4741969. 474196926473375 Open DOISearch in Google Scholar

[104] Heinicke U, Fulda S. Chemosensitization of rhabdomyosarcoma cells by the histone deacetylase inhibitor SAHA. Cancer Lett. 2014 Aug 28;351(1):50–58. doi:10.1016/j.canlet.2014.04.021. Epub 2014 May 6. PMID: 24814395. HeinickeU FuldaS Chemosensitization of rhabdomyosarcoma cells by the histone deacetylase inhibitor SAHA Cancer Lett 2014 Aug 28 351 1 50 58 10.1016/j.canlet.2014.04.021 Epub 2014 May 6. PMID: 24814395. 24814395 Open DOISearch in Google Scholar

[105] Sampson VB, Vetter NS, Kamara DF, Collier AB, Gresh RC, Kolb EA. Vorinostat enhances cytotoxicity of SN-38 and temozolomide in Ewing sarcoma cells and activates STAT3/AKT/MAPK pathways. PLoS One. 2015 Nov 16;10(11):e0142704. doi:10.1371/journal.pone.0142704. PMID: 26571493; PMCID: PMC4646493. SampsonVB VetterNS KamaraDF CollierAB GreshRC KolbEA Vorinostat enhances cytotoxicity of SN-38 and temozolomide in Ewing sarcoma cells and activates STAT3/AKT/MAPK pathways PLoS One 2015 Nov 16 10 11 e0142704 10.1371/journal.pone.0142704 PMID: 26571493; PMCID: PMC4646493. 464649326571493 Open DOISearch in Google Scholar

[106] Unland R, Clemens D, Heinicke U, Potratz JC, Hotfilder M, Fulda S, et al. Suberoylanilide hydroxamic acid synergistically enhances the antitumor activity of etoposide in Ewing sarcoma cell lines. Anticancer Drugs. 2015 Sep;26(8):843–851. doi:10.1097/CAD.0000000000000256. PMID: 26053276. UnlandR ClemensD HeinickeU PotratzJC HotfilderM FuldaS Suberoylanilide hydroxamic acid synergistically enhances the antitumor activity of etoposide in Ewing sarcoma cell lines Anticancer Drugs 2015 Sep 26 8 843 851 10.1097/CAD.0000000000000256 PMID: 26053276. 26053276 Open DOISearch in Google Scholar

[107] Schonn I, Hennesen J, Dartsch DC. Ku70 and Rad51 vary in their importance for the repair of doxorubicin-versus etoposide-induced DNA damage. Apoptosis. 2011 Apr;16(4):359–369. doi:10.1007/s10495-010-0564-y. PMID: 21107697. SchonnI HennesenJ DartschDC Ku70 and Rad51 vary in their importance for the repair of doxorubicin-versus etoposide-induced DNA damage Apoptosis 2011 Apr 16 4 359 369 10.1007/s10495-010-0564-y PMID: 21107697. 21107697 Open DOISearch in Google Scholar

[108] Lopez G, Liu J, Ren W, Wei W, Wang S, Lahat G, et al. Combining PCI-24781, a novel histone deacetylase inhibitor, with chemotherapy for the treatment of soft tissue sarcoma. Clin Cancer Res. 2009 May 15;15(10):3472–83. doi:10.1158/1078-0432.CCR-08-2714. Epub 2009 May 5. Erratum in Clin Cancer Res. 2015 Apr 1;21(7):1774–1775. PMID: 19417021. LopezG LiuJ RenW WeiW WangS LahatG Combining PCI-24781, a novel histone deacetylase inhibitor, with chemotherapy for the treatment of soft tissue sarcoma Clin Cancer Res 2009 May 15 15 10 3472 83 10.1158/1078-0432.CCR-08-2714 Epub 2009 May 5. Erratum in Clin Cancer Res. 2015 Apr 1;21(7):1774–1775. PMID: 19417021. 19417021 Open DOISearch in Google Scholar

[109] Becker M, Graf C, Tonak M, Radsak MP, Bopp T, Bals R, et al. Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents. Oncol Lett. 2016 Aug;12(2):1257–1264. doi:10.3892/ol.2016.4784. Epub 2016 Jun 24. PMID: 27446424; PMCID: PMC4950181. BeckerM GrafC TonakM RadsakMP BoppT BalsR Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents Oncol Lett 2016 Aug 12 2 1257 1264 10.3892/ol.2016.4784 Epub 2016 Jun 24. PMID: 27446424; PMCID: PMC4950181. 495018127446424 Open DOISearch in Google Scholar

[110] Yang C, Choy E, Hornicek FJ, Wood KB, Schwab JH, Liu X, et al. Histone deacetylase inhibitor (HDACI) PCI-24781 potentiates cytotoxic effects of doxorubicin in bone sarcoma cells. Cancer Chemother Pharmacol. 2011 Feb;67(2):439–446. doi:10.1007/s00280-010-1344-7. Epub 2010 May 12. PMID: 20461381. YangC ChoyE HornicekFJ WoodKB SchwabJH LiuX Histone deacetylase inhibitor (HDACI) PCI-24781 potentiates cytotoxic effects of doxorubicin in bone sarcoma cells Cancer Chemother Pharmacol 2011 Feb 67 2 439 446 10.1007/s00280-010-1344-7 Epub 2010 May 12. PMID: 20461381. 20461381 Open DOISearch in Google Scholar

[111] Capobianco E, Mora A, La Sala D, Roberti A, Zaki N, et al. Separate and combined effects of DNMT and HDAC inhibitors in treating human multi-drug resistant osteosarcoma HosDXR150 cell line. PLoS One. 2014 Apr 22;9(4):e95596. doi:10.1371/journal.pone.0095596. PMID: 24756038; PMCID: PMC3995708. CapobiancoE MoraA La SalaD RobertiA ZakiN Separate and combined effects of DNMT and HDAC inhibitors in treating human multi-drug resistant osteosarcoma HosDXR150 cell line PLoS One 2014 Apr 22 9 4 e95596 10.1371/journal.pone.0095596 PMID: 24756038; PMCID: PMC3995708. 399570824756038 Open DOISearch in Google Scholar

[112] Nakamura T, Matsumine A, Kawai A, Araki N, Goto T, Yonemoto T, et al. The clinical outcome of pazopanib treatment in Japanese patients with relapsed soft tissue sarcoma: A Japanese Musculoskeletal Oncology Group (JMOG) study. Cancer. 2016 May 1;122(9):1408–1416. doi:10.1002/cncr.29961. Epub 2016 Mar 11. PMID: 26970174; PMCID: PMC5069581. NakamuraT MatsumineA KawaiA ArakiN GotoT YonemotoT The clinical outcome of pazopanib treatment in Japanese patients with relapsed soft tissue sarcoma: A Japanese Musculoskeletal Oncology Group (JMOG) study Cancer 2016 May 1 122 9 1408 1416 10.1002/cncr.29961 Epub 2016 Mar 11. PMID: 26970174; PMCID: PMC5069581. 506958126970174 Open DOISearch in Google Scholar

[113] Loganathan SN, Tang N, Fleming JT, Ma Y, Guo Y, Borinstein SC, et al. BET bromodomain inhibitors suppress EWS-FLI1-dependent transcription and the IGF1 autocrine mechanism in Ewing sarcoma. Oncotarget. 2016 Jul 12;7(28):43504–43517. doi:10.18632/oncotarget.9762. PMID: 27259270; PMCID: PMC5190040. LoganathanSN TangN FlemingJT MaY GuoY BorinsteinSC BET bromodomain inhibitors suppress EWS-FLI1-dependent transcription and the IGF1 autocrine mechanism in Ewing sarcoma Oncotarget 2016 Jul 12 7 28 43504 43517 10.18632/oncotarget.9762 PMID: 27259270; PMCID: PMC5190040. 519004027259270 Open DOISearch in Google Scholar

[114] Hensel T, Giorgi C, Schmidt O, Calzada-Wack J, Neff F, Buch T, Niggli FK, et al. Targeting the EWS-ETS transcriptional program by BET bromodomain inhibition in Ewing sarcoma. Oncotarget. 2016 Jan 12;7(2):1451–1463. doi:10.18632/oncotarget.6385. PMID: 26623725; PMCID: PMC4811472. HenselT GiorgiC SchmidtO Calzada-WackJ NeffF BuchT NiggliFK Targeting the EWS-ETS transcriptional program by BET bromodomain inhibition in Ewing sarcoma Oncotarget 2016 Jan 12 7 2 1451 1463 10.18632/oncotarget.6385 PMID: 26623725; PMCID: PMC4811472. 481147226623725 Open DOISearch in Google Scholar

[115] Pedersen MT, Helin K. Histone demethylases in development and disease. Trends Cell Biol. 2010 Nov;20(11):662–671. doi:10.1016/j.tcb.2010.08.011. Epub 2010 Sep 20. PMID: 20863703. PedersenMT HelinK Histone demethylases in development and disease Trends Cell Biol 2010 Nov 20 11 662 671 10.1016/j.tcb.2010.08.011 Epub 2010 Sep 20. PMID: 20863703. 20863703 Open DOISearch in Google Scholar

[116] Chen Y, Jie W, Yan W, Zhou K, Xiao Y. Lysine-specific histone demethylase 1 (LSD1): A potential molecular target for tumor therapy. Crit Rev Eukaryot Gene Expr. 2012;22(1):53–59. doi:10.1615/critreveukargeneexpr.v22.i1.40. PMID: 22339659. ChenY JieW YanW ZhouK XiaoY Lysine-specific histone demethylase 1 (LSD1): A potential molecular target for tumor therapy Crit Rev Eukaryot Gene Expr 2012 22 1 53 59 10.1615/critreveukargeneexpr.v22.i1.40 PMID: 22339659. 22339659 Open DOISearch in Google Scholar

[117] Theisen ER, Pishas KI, Saund RS, Lessnick SL. Therapeutic opportunities in Ewing sarcoma: EWS-FLI inhibition via LSD1 targeting. Oncotarget. 2016 Apr 5;7(14):17616–17630. doi:10.18632/oncotarget.7124. PMID: 26848860; PMCID: PMC4951237. TheisenER PishasKI SaundRS LessnickSL Therapeutic opportunities in Ewing sarcoma: EWS-FLI inhibition via LSD1 targeting Oncotarget 2016 Apr 5 7 14 17616 17630 10.18632/oncotarget.7124 PMID: 26848860; PMCID: PMC4951237. 495123726848860 Open DOISearch in Google Scholar

[118] Spriano F, Chung EYL, Gaudio E, Tarantelli C, Cascione L, Napoli S, et al. The ETS inhibitors YK-4-279 and TK-216 are novel antilymphoma agents. Clin Cancer Res. 2019 Aug 15;25(16):5167–5176. doi:10.1158/1078-0432.CCR-18-2718. Epub 2019 Jun 10. PMID: 31182435. SprianoF ChungEYL GaudioE TarantelliC CascioneL NapoliS The ETS inhibitors YK-4-279 and TK-216 are novel antilymphoma agents Clin Cancer Res 2019 Aug 15 25 16 5167 5176 10.1158/1078-0432.CCR-18-2718 Epub 2019 Jun 10. PMID: 31182435. 31182435 Open DOISearch in Google Scholar

[119] Stega J, Noel MS, Vandell AG, Stega D, Del Priore G, Hoffman S. A first-in-human study of the novel metabolism-based anti-cancer agent SM-88 in subjects with advanced metastatic cancer. Invest New Drugs. 2020 Apr;38(2):392–401. doi:10.1007/s10637-019-00758-8. Epub 2019 Mar 30. PMID: 30929156; PMCID: PMC7066285. StegaJ NoelMS VandellAG StegaD Del PrioreG HoffmanS A first-in-human study of the novel metabolism-based anti-cancer agent SM-88 in subjects with advanced metastatic cancer Invest New Drugs 2020 Apr 38 2 392 401 10.1007/s10637-019-00758-8 Epub 2019 Mar 30. PMID: 30929156; PMCID: PMC7066285. 706628530929156 Open DOISearch in Google Scholar

[120] Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993 Dec 16;366(6456):704–707. doi:10.1038/366704a0. PMID: 8259215. SerranoM HannonGJ BeachD A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4 Nature 1993 Dec 16 366 6456 704 707 10.1038/366704a0 PMID: 8259215. 8259215 Open DOISearch in Google Scholar

[121] Kennedy AL, Vallurupalli M, Chen L, Crompton B, Cowley G, Vazquez F, et al. Functional, chemical genomic, and super-enhancer screening identify sensitivity to cyclin D1/CDK4 pathway inhibition in Ewing sarcoma. Oncotarget. 2015 Oct 6;6(30):30178–30193. doi:10.18632/oncotarget.4903. PMID: 26337082; PMCID: PMC4745789. KennedyAL VallurupalliM ChenL CromptonB CowleyG VazquezF Functional, chemical genomic, and super-enhancer screening identify sensitivity to cyclin D1/CDK4 pathway inhibition in Ewing sarcoma Oncotarget 2015 Oct 6 6 30 30178 30193 10.18632/oncotarget.4903 PMID: 26337082; PMCID: PMC4745789. 474578926337082 Open DOISearch in Google Scholar

[122] Dowless M, Lowery CD, Shackleford T, Renschler M, Stephens J, Flack R, et al. Abemaciclib is active in preclinical models of Ewing sarcoma via multipronged regulation of cell cycle, DNA methylation, and interferon pathway signaling. Clin Cancer Res. 2018 Dec 1;24(23):6028–6039. doi:10.1158/1078-0432.CCR-18-1256. Epub 2018 Aug 21. PMID: 30131386; PMCID: PMC6279561. DowlessM LoweryCD ShacklefordT RenschlerM StephensJ FlackR Abemaciclib is active in preclinical models of Ewing sarcoma via multipronged regulation of cell cycle, DNA methylation, and interferon pathway signaling Clin Cancer Res 2018 Dec 1 24 23 6028 6039 10.1158/1078-0432.CCR-18-1256 Epub 2018 Aug 21. PMID: 30131386; PMCID: PMC6279561. 627956130131386 Open DOISearch in Google Scholar

[123] Oliner JD, Pietenpol JA, Thiagalingam S, Gyuris J, Kinzler KW, Vogelstein B. Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature. 1993 Apr 29;362(6423):857–860. doi:10.1038/362857a0. PMID: 8479525. OlinerJD PietenpolJA ThiagalingamS GyurisJ KinzlerKW VogelsteinB Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53 Nature 1993 Apr 29 362 6423 857 860 10.1038/362857a0 PMID: 8479525. 8479525 Open DOISearch in Google Scholar

[124] Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC, et al. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell. 2004 Nov 24;119(5):591–602. doi:10.1016/j.cell.2004.11.022. PMID: 15550242. BondGL HuW BondEE RobinsH LutzkerSG ArvaNC A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans Cell 2004 Nov 24 119 5 591 602 10.1016/j.cell.2004.11.022 PMID: 15550242. 15550242 Open DOISearch in Google Scholar

[125] Shi D, Gu W. Dual roles of MDM2 in the regulation of p53: Ubiquitination dependent and ubiquitination independent mechanisms of MDM2 repression of p53 activity. Genes Cancer. 2012 Mar;3(3–4):240–248. doi:10.1177/1947601912455199. PMID: 23150757; PMCID: PMC3494363. ShiD GuW Dual roles of MDM2 in the regulation of p53: Ubiquitination dependent and ubiquitination independent mechanisms of MDM2 repression of p53 activity Genes Cancer 2012 Mar 3 3–4 240 248 10.1177/1947601912455199 PMID: 23150757; PMCID: PMC3494363. 349436323150757 Open DOISearch in Google Scholar

[126] Pishas KI, Al-Ejeh F, Zinonos I, Kumar R, Evdokiou A, Brown MP, et al. Nutlin-3a is a potential therapeutic for Ewing sarcoma. Clin Cancer Res. 2011 Feb 1;17(3):494–504. doi:10.1158/1078-0432.CCR-10-1587. Epub 2010 Nov 23. PMID: 21098696. PishasKI Al-EjehF ZinonosI KumarR EvdokiouA BrownMP Nutlin-3a is a potential therapeutic for Ewing sarcoma Clin Cancer Res 2011 Feb 1 17 3 494 504 10.1158/1078-0432.CCR-10-1587 Epub 2010 Nov 23. PMID: 21098696. 21098696 Open DOISearch in Google Scholar

[127] Wang H, Ma X, Ren S, Buolamwini JK, Yan C. A small-molecule inhibitor of MDMX activates p53 and induces apoptosis. Mol Cancer Ther. 2011 Jan;10(1):69–79. doi:10.1158/1535-7163.MCT-10-0581. Epub 2010 Nov 12. PMID: 21075910; PMCID: PMC3058295. WangH MaX RenS BuolamwiniJK YanC A small-molecule inhibitor of MDMX activates p53 and induces apoptosis Mol Cancer Ther 2011 Jan 10 1 69 79 10.1158/1535-7163.MCT-10-0581 Epub 2010 Nov 12. PMID: 21075910; PMCID: PMC3058295. 305829521075910 Open DOISearch in Google Scholar

[128] Depping R, von Fallois M, Landesman Y, Kosyna FK. The nuclear export inhibitor selinexor inhibits hypoxia signaling pathways and 3D spheroid growth of cancer cells. Onco Targets Ther. 2019 Oct 11;12:8387–8399. doi:10.2147/OTT.S213208. PMID: 31632086; PMCID: PMC6793465. DeppingR von FalloisM LandesmanY KosynaFK The nuclear export inhibitor selinexor inhibits hypoxia signaling pathways and 3D spheroid growth of cancer cells Onco Targets Ther 2019 Oct 11 12 8387 8399 10.2147/OTT.S213208 PMID: 31632086; PMCID: PMC6793465. 679346531632086 Open DOISearch in Google Scholar

[129] Gounder MM, Zer A, Tap WD, Salah S, Dickson MA, Gupta AA, et al. Phase IB study of selinexor, a first-in-class inhibitor of nuclear export, in patients with advanced refractory bone or soft tissue sarcoma. J Clin Oncol. 2016 Sep 10;34(26):3166–3174. doi:10.1200/JCO.2016.67.6346. Epub 2016 Jul 25. Erratum in J Clin Oncol. 2017 Mar;35(7):812. PMID: 27458288; PMCID: PMC5321073. GounderMM ZerA TapWD SalahS DicksonMA GuptaAA Phase IB study of selinexor, a first-in-class inhibitor of nuclear export, in patients with advanced refractory bone or soft tissue sarcoma J Clin Oncol 2016 Sep 10 34 26 3166 3174 10.1200/JCO.2016.67.6346 Epub 2016 Jul 25. Erratum in J Clin Oncol. 2017 Mar;35(7):812. PMID: 27458288; PMCID: PMC5321073. 532107327458288 Open DOISearch in Google Scholar

[130] Taylor-Kashton C, Lichtensztejn D, Baloglu E, Senapedis W, Shacham S, Kauffman MG, et al. XPO1 inhibition preferentially disrupts the 3D nuclear organization of telomeres in tumor cells. J Cell Physiol. 2016 Dec;231(12):2711–2719. doi:10.1002/jcp.25378. Epub 2016 Apr 8. PMID: 26991404; PMCID: PMC5111786. Taylor-KashtonC LichtensztejnD BalogluE SenapedisW ShachamS KauffmanMG XPO1 inhibition preferentially disrupts the 3D nuclear organization of telomeres in tumor cells J Cell Physiol 2016 Dec 231 12 2711 2719 10.1002/jcp.25378 Epub 2016 Apr 8. PMID: 26991404; PMCID: PMC5111786. 511178626991404 Open DOISearch in Google Scholar

[131] Nakayama R, Zhang YX, Czaplinski JT, Anatone AJ, Sicinska ET, Fletcher JA, et al. Preclinical activity of selinexor, an inhibitor of XPO1, in sarcoma. Oncotarget. 2016 Mar 29;7(13):16581–16592. doi:10.18632/oncotarget.7667. PMID: 26918731; PMCID: PMC4941336. NakayamaR ZhangYX CzaplinskiJT AnatoneAJ SicinskaET FletcherJA Preclinical activity of selinexor, an inhibitor of XPO1, in sarcoma Oncotarget 2016 Mar 29 7 13 16581 16592 10.18632/oncotarget.7667 PMID: 26918731; PMCID: PMC4941336. 494133626918731 Open DOISearch in Google Scholar

[132] Nair JS, Musi E, Schwartz GK. Selinexor (KPT-330) induces tumor suppression through nuclear sequestration of IκB and downregulation of survivin. Clin Cancer Res. 2017 Aug 1;23(15):4301–4311. doi:10.1158/1078-0432.CCR-16-2632. Epub 2017 Mar 17. PMID: 28314790. NairJS MusiE SchwartzGK Selinexor (KPT-330) induces tumor suppression through nuclear sequestration of IκB and downregulation of survivin Clin Cancer Res 2017 Aug 1 23 15 4301 4311 10.1158/1078-0432.CCR-16-2632 Epub 2017 Mar 17. PMID: 28314790. 28314790 Open DOISearch in Google Scholar

[133] Kashyap T, Argueta C, Aboukameel A, Unger TJ, Klebanov B, Mohammad RM, et al. Selinexor, a selective inhibitor of nuclear export (SINE) compound, acts through NF-κB deactivation and combines with proteasome inhibitors to synergistically induce tumor cell death. Oncotarget. 2016 Nov 29;7(48):78883–78895. doi:10.18632/oncotarget.12428. PMID: 27713151; PMCID: PMC5346685. KashyapT ArguetaC AboukameelA UngerTJ KlebanovB MohammadRM Selinexor, a selective inhibitor of nuclear export (SINE) compound, acts through NF-κB deactivation and combines with proteasome inhibitors to synergistically induce tumor cell death Oncotarget 2016 Nov 29 7 48 78883 78895 10.18632/oncotarget.12428 PMID: 27713151; PMCID: PMC5346685. 534668527713151 Open DOISearch in Google Scholar

[134] Ahmed AA, Sherman AK, Pawel BR. Expression of therapeutic targets in Ewing sarcoma family tumors. Hum Pathol. 2012 Jul;43(7):1077–1083. doi:10.1016/j.humpath.2011.09.001. Epub 2011 Dec 21. PMID: 22196127. AhmedAA ShermanAK PawelBR Expression of therapeutic targets in Ewing sarcoma family tumors Hum Pathol 2012 Jul 43 7 1077 1083 10.1016/j.humpath.2011.09.001 Epub 2011 Dec 21. PMID: 22196127. 22196127 Open DOISearch in Google Scholar

[135] Mita MM, Mita AC, Chu QS, Rowinsky EK, Fetterly GJ, Goldston M, et al. Phase I trial of the novel mammalian target of rapamycin inhibitor deforolimus (AP23573; MK-8669) administered intravenously daily for 5 days every 2 weeks to patients with advanced malignancies. J Clin Oncol. 2008 Jan 20;26(3):361–67. doi:10.1200/JCO.2007.12.0345. PMID: 18202410. MitaMM MitaAC ChuQS RowinskyEK FetterlyGJ GoldstonM Phase I trial of the novel mammalian target of rapamycin inhibitor deforolimus (AP23573; MK-8669) administered intravenously daily for 5 days every 2 weeks to patients with advanced malignancies J Clin Oncol 2008 Jan 20 26 3 361 67 10.1200/JCO.2007.12.0345 PMID: 18202410. 18202410 Open DOISearch in Google Scholar

[136] Bagatell R, Norris R, Ingle AM, Ahern C, Voss S, Fox E, et al. Phase 1 trial of temsirolimus in combination with irinotecan and temozolomide in children, adolescents and young adults with relapsed or refractory solid tumors: A Children's Oncology Group Study. Pediatr Blood Cancer. 2014 May;61(5):833–839. doi:10.1002/pbc.24874. Epub 2013 Nov 19. PMID: 24249672; PMCID: PMC4196713. BagatellR NorrisR IngleAM AhernC VossS FoxE Phase 1 trial of temsirolimus in combination with irinotecan and temozolomide in children, adolescents and young adults with relapsed or refractory solid tumors: A Children's Oncology Group Study Pediatr Blood Cancer 2014 May 61 5 833 839 10.1002/pbc.24874 Epub 2013 Nov 19. PMID: 24249672; PMCID: PMC4196713. 419671324249672 Open DOISearch in Google Scholar

[137] Trucco MM, Meyer CF, Thornton KA, Shah P, Chen AR, Wilky BA, et al. A phase II study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcomas. Clin Sarcoma Res. 2018 Nov 5;8:21. doi:10.1186/s13569-018-0107-9. PMID: 30410720; PMCID: PMC6217787. TruccoMM MeyerCF ThorntonKA ShahP ChenAR WilkyBA A phase II study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcomas Clin Sarcoma Res 2018 Nov 5 8 21 10.1186/s13569-018-0107-9 PMID: 30410720; PMCID: PMC6217787. 621778730410720 Open DOISearch in Google Scholar

[138] Prieur A, Tirode F, Cohen P, Delattre O. EWS/FLI-1 silencing and gene profiling of Ewing cells reveal downstream oncogenic pathways and a crucial role for repression of insulin-like growth factor binding protein 3. Mol Cell Biol. 2004 Aug;24(16):7275–7283. doi:10.1128/MCB.24.16.7275-7283.2004. PMID: 15282325; PMCID: PMC479730. PrieurA TirodeF CohenP DelattreO EWS/FLI-1 silencing and gene profiling of Ewing cells reveal downstream oncogenic pathways and a crucial role for repression of insulin-like growth factor binding protein 3 Mol Cell Biol 2004 Aug 24 16 7275 7283 10.1128/MCB.24.16.7275-7283.2004 PMID: 15282325; PMCID: PMC479730. 47973015282325 Open DOISearch in Google Scholar

[139] Scotlandi K, Benini S, Sarti M, Serra M, Lollini PL, Maurici D, et al. Insulin-like growth factor I receptor-mediated circuit in Ewing's sarcoma/peripheral neuroectodermal tumor: A possible therapeutic target. Cancer Res. 1996 Oct 15;56(20):4570–4574. PMID: 8840962. ScotlandiK BeniniS SartiM SerraM LolliniPL MauriciD Insulin-like growth factor I receptor-mediated circuit in Ewing's sarcoma/peripheral neuroectodermal tumor: A possible therapeutic target Cancer Res 1996 Oct 15 56 20 4570 4574 PMID: 8840962. Search in Google Scholar

[140] Kang HG, Jenabi JM, Liu XF, Reynolds CP, Triche TJ, Sorensen PH. Inhibition of the insulin-like growth factor I receptor by epigallocatechin gallate blocks proliferation and induces the death of Ewing tumor cells. Mol Cancer Ther. 2010 May;9(5):1396–1407. doi:10.1158/1535-7163.MCT-09-0604. Epub 2010 Apr 27. PMID: 20423994. KangHG JenabiJM LiuXF ReynoldsCP TricheTJ SorensenPH Inhibition of the insulin-like growth factor I receptor by epigallocatechin gallate blocks proliferation and induces the death of Ewing tumor cells Mol Cancer Ther 2010 May 9 5 1396 1407 10.1158/1535-7163.MCT-09-0604 Epub 2010 Apr 27. PMID: 20423994. 20423994 Open DOISearch in Google Scholar

[141] Manara MC, Landuzzi L, Nanni P, Nicoletti G, Zambelli D, Lollini PL, et al. Preclinical in vivo study of new insulin-like growth factor-I receptor-specific inhibitor in Ewing's sarcoma. Clin Cancer Res. 2007 Feb 15;13(4):1322–1330. doi:10.1158/1078-0432.CCR-06-1518. PMID: 17317844 ManaraMC LanduzziL NanniP NicolettiG ZambelliD LolliniPL Preclinical in vivo study of new insulin-like growth factor-I receptor-specific inhibitor in Ewing's sarcoma Clin Cancer Res 2007 Feb 15 13 4 1322 1330 10.1158/1078-0432.CCR-06-1518 PMID: 17317844 17317844 Open DOISearch in Google Scholar

[142] Scotlandi K, Benini S, Nanni P, Lollini PL, Nicoletti G, Landuzzi L, et al. Blockage of insulin-like growth factor-I receptor inhibits the growth of Ewing's sarcoma in athymic mice. Cancer Res. 1998 Sep 15;58(18):4127–4131. PMID: 9751624. ScotlandiK BeniniS NanniP LolliniPL NicolettiG LanduzziL Blockage of insulin-like growth factor-I receptor inhibits the growth of Ewing's sarcoma in athymic mice Cancer Res 1998 Sep 15 58 18 4127 4131 PMID: 9751624. Search in Google Scholar

[143] Tolcher AW, Sarantopoulos J, Patnaik A, Papadopoulos K, Lin CC, Rodon J, et al. Phase I, pharmacokinetic, and pharmacodynamic study of AMG 479, a fully human monoclonal antibody to insulin-like growth factor receptor 1. J Clin Oncol. 2009 Dec 1;27(34):5800–5807. doi:10.1200/JCO.2009.23.6745. Epub 2009 Sep 28. PMID: 19786654. TolcherAW SarantopoulosJ PatnaikA PapadopoulosK LinCC RodonJ Phase I, pharmacokinetic, and pharmacodynamic study of AMG 479, a fully human monoclonal antibody to insulin-like growth factor receptor 1 J Clin Oncol 2009 Dec 1 27 34 5800 5807 10.1200/JCO.2009.23.6745 Epub 2009 Sep 28. PMID: 19786654. 19786654 Open DOISearch in Google Scholar

[144] Tap WD, Demetri G, Barnette P, Desai J, Kavan P, Tozer R, et al. Phase II study of ganitumab, a fully human anti-type-1 insulin-like growth factor receptor antibody, in patients with metastatic Ewing family tumors or desmoplastic small round cell tumors. J Clin Oncol. 2012 May 20;30(15):1849–1856. doi:10.1200/JCO.2011.37.2359. Epub 2012 Apr 16. PMID: 22508822. TapWD DemetriG BarnetteP DesaiJ KavanP TozerR Phase II study of ganitumab, a fully human anti-type-1 insulin-like growth factor receptor antibody, in patients with metastatic Ewing family tumors or desmoplastic small round cell tumors J Clin Oncol 2012 May 20 30 15 1849 1856 10.1200/JCO.2011.37.2359 Epub 2012 Apr 16. PMID: 22508822. 22508822 Open DOISearch in Google Scholar

[145] Rajabi M, Mousa SA. The role of angiogenesis in cancer treatment. Biomedicines. 2017 Jun 21;5(2):34. doi:10.3390/biomedicines5020034. PMID: 28635679; PMCID: PMC5489820. RajabiM MousaSA The role of angiogenesis in cancer treatment Biomedicines 2017 Jun 21 5 2 34 10.3390/biomedicines5020034 PMID: 28635679; PMCID: PMC5489820. 548982028635679 Open DOISearch in Google Scholar

[146] DuBois SG, Marina N, Glade-Bender J. Angiogenesis and vascular targeting in Ewing sarcoma: A review of preclinical and clinical data. Cancer. 2010 Feb 1;116(3):749–757. doi:10.1002/cncr.24844. PMID: 20029966; PMCID: PMC2815027. DuBoisSG MarinaN Glade-BenderJ Angiogenesis and vascular targeting in Ewing sarcoma: A review of preclinical and clinical data Cancer 2010 Feb 1 116 3 749 757 10.1002/cncr.24844 PMID: 20029966; PMCID: PMC2815027. 281502720029966 Open DOISearch in Google Scholar

[147] Zhou Z, Bolontrade MF, Reddy K, Duan X, Guan H, Yu L, et al. Suppression of Ewing's sarcoma tumor growth, tumor vessel formation, and vasculogenesis following anti vascular endothelial growth factor receptor-2 therapy. Clin Cancer Res. 2007 Aug 15;13(16):4867–4873. doi:10.1158/1078-0432.CCR-07-0133. PMID: 17699866. ZhouZ BolontradeMF ReddyK DuanX GuanH YuL Suppression of Ewing's sarcoma tumor growth, tumor vessel formation, and vasculogenesis following anti vascular endothelial growth factor receptor-2 therapy Clin Cancer Res 2007 Aug 15 13 16 4867 4873 10.1158/1078-0432.CCR-07-0133 PMID: 17699866. 17699866 Open DOISearch in Google Scholar

[148] Reddy K, Zhou Z, Schadler K, Jia SF, Kleinerman ES. Bone marrow subsets differentiate into endothelial cells and pericytes contributing to Ewing's tumor vessels. Mol Cancer Res. 2008 Jun;6(6):929–936. doi:10.1158/1541-7786.MCR-07-2189. PMID: 18567797; PMCID: PMC2441901. ReddyK ZhouZ SchadlerK JiaSF KleinermanES Bone marrow subsets differentiate into endothelial cells and pericytes contributing to Ewing's tumor vessels Mol Cancer Res 2008 Jun 6 6 929 936 10.1158/1541-7786.MCR-07-2189 PMID: 18567797; PMCID: PMC2441901. 244190118567797 Open DOISearch in Google Scholar

[149] Potikyan G, Savene RO, Gaulden JM, France KA, Zhou Z, Kleinerman ES, et al. EWS/FLI1 regulates tumor angiogenesis in Ewing's sarcoma via suppression of thrombospondins. Cancer Res. 2007 Jul 15;67(14):6675–6684. doi:10.1158/0008-5472.CAN-06-4140. PMID: 17638877. PotikyanG SaveneRO GauldenJM FranceKA ZhouZ KleinermanES EWS/FLI1 regulates tumor angiogenesis in Ewing's sarcoma via suppression of thrombospondins Cancer Res 2007 Jul 15 67 14 6675 6684 10.1158/0008-5472.CAN-06-4140 PMID: 17638877. 17638877 Open DOISearch in Google Scholar

[150] Bukowski RM, Yasothan U, Kirkpatrick P, Pazopanib. Nat Rev Drug Discov. 2010 Jan;9(1):17–18. doi:10.1038/nrd3073. PMID: 20043026. BukowskiRM YasothanU KirkpatrickP Pazopanib Nat Rev Drug Discov 2010 Jan 9 1 17 18 10.1038/nrd3073 PMID: 20043026. 20043026 Open DOISearch in Google Scholar

[151] van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, et al., EORTC Soft Tissue and Bone Sarcoma Group, PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879–1886. doi:10.1016/S0140-6736(12)60651-5. Epub 2012 May 16. PMID: 22595799. van der GraafWT BlayJY ChawlaSP KimDW Bui-NguyenB CasaliPG EORTC Soft Tissue and Bone Sarcoma Group PALETTE study group Pazopanib for metastatic soft-tissue sarcoma (PALETTE): A randomised, double-blind, placebo-controlled phase 3 trial Lancet 2012 May 19 379 9829 1879 1886 10.1016/S0140-6736(12)60651-5 Epub 2012 May 16. PMID: 22595799. 22595799 Open DOISearch in Google Scholar

[152] Alcindor T. Response of refractory Ewing sarcoma to pazopanib. Acta Oncol. 2015 Jul;54(7):1063–1064. doi:10.3109/0284186X.2014.971938. Epub 2014 Oct 27. PMID: 25345493. AlcindorT Response of refractory Ewing sarcoma to pazopanib Acta Oncol 2015 Jul 54 7 1063 1064 10.3109/0284186X.2014.971938 Epub 2014 Oct 27. PMID: 25345493. 25345493 Open DOISearch in Google Scholar

[153] Attia S, Okuno SH, Robinson SI, Webber NP, Indelicato DJ, Jones RL, et al. Clinical activity of pazopanib in metastatic extraosseous Ewing sarcoma. Rare Tumors. 2015 May 21;7(2):5992. doi:10.4081/rt.2015.5992. PMID: 26266019; PMCID: PMC4508650. AttiaS OkunoSH RobinsonSI WebberNP IndelicatoDJ JonesRL Clinical activity of pazopanib in metastatic extraosseous Ewing sarcoma Rare Tumors 2015 May 21 7 2 5992 10.4081/rt.2015.5992 PMID: 26266019; PMCID: PMC4508650. 450865026266019 Open DOISearch in Google Scholar

[154] Yamamoto Y, Nozawa M, Shimizu N, Minami T, Yoshimura K, Uemura H. Pazopanib for recurrent extraosseous Ewing's sarcoma of the retroperitoneum. Int J Urol. 2014 Nov;21(11):1183–1184. doi:10.1111/iju.12546. Epub 2014 Jul 8. PMID: 25040171. YamamotoY NozawaM ShimizuN MinamiT YoshimuraK UemuraH Pazopanib for recurrent extraosseous Ewing's sarcoma of the retroperitoneum Int J Urol 2014 Nov 21 11 1183 1184 10.1111/iju.12546 Epub 2014 Jul 8. PMID: 25040171. 25040171 Open DOISearch in Google Scholar

[155] Dembla V, Groisberg R, Hess K, Fu S, Wheler J, Hong DS, et al. Outcomes of patients with sarcoma enrolled in clinical trials of pazopanib combined with histone deacetylase, mTOR, Her2, or MEK inhibitors. Sci Rep. 2017 Nov 21;7(1):15963. doi:10.1038/s41598-017-13114-8. PMID: 29162825; PMCID: PMC5698336. DemblaV GroisbergR HessK FuS WhelerJ HongDS Outcomes of patients with sarcoma enrolled in clinical trials of pazopanib combined with histone deacetylase, mTOR, Her2, or MEK inhibitors Sci Rep 2017 Nov 21 7 1 15963 10.1038/s41598-017-13114-8 PMID: 29162825; PMCID: PMC5698336. 569833629162825 Open DOISearch in Google Scholar

[156] Keir ST, Morton CL, Wu J, Kurmasheva RT, Houghton PJ, Smith MA. Initial testing of the multitargeted kinase inhibitor pazopanib by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer. 2012 Sep;59(3):586–588. doi:10.1002/pbc.24016. Epub 2011 Dec 20. PMID: 22190407; PMCID: PMC4245051. KeirST MortonCL WuJ KurmashevaRT HoughtonPJ SmithMA Initial testing of the multitargeted kinase inhibitor pazopanib by the Pediatric Preclinical Testing Program Pediatr Blood Cancer 2012 Sep 59 3 586 588 10.1002/pbc.24016 Epub 2011 Dec 20. PMID: 22190407; PMCID: PMC4245051. 424505122190407 Open DOISearch in Google Scholar

[157] Smith M, Kang M, Reynolds P, Gorlick R, Kolb A, Maris J, et al. Abstract LB-353: Pediatric Preclinical Testing Program (PPTP) stage 1 evaluation of cabozantinib. Cancer Res. 2013 Apr 15; 73(8 Suppl.):LB-353. doi:10.1158/1538-7445.AM2013-LB-353. SmithM KangM ReynoldsP GorlickR KolbA MarisJ Abstract LB-353: Pediatric Preclinical Testing Program (PPTP) stage 1 evaluation of cabozantinib Cancer Res 2013 Apr 15 73 8 Suppl. LB-353 10.1158/1538-7445.AM2013-LB-353 Open DOISearch in Google Scholar

[158] Italiano A, Mir O, Mathoulin-Pelissier S, Penel N, Piperno-Neumann S, Bompas E, et al. Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): A multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020 Mar;21(3):446–455. doi:10.1016/S1470-2045(19)30825-3. Epub 2020 Feb 17. PMID: 32078813. ItalianoA MirO Mathoulin-PelissierS PenelN Piperno-NeumannS BompasE Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): A multicentre, single-arm, phase 2 trial Lancet Oncol 2020 Mar 21 3 446 455 10.1016/S1470-2045(19)30825-3 Epub 2020 Feb 17. PMID: 32078813. 876361632078813 Open DOISearch in Google Scholar

[159] Davis LE, Bolejack V, Ryan CW, Ganjoo KN, Loggers ET, Chawla S, et al. Randomized double-blind phase II study of regorafenib in patients with metastatic osteosarcoma. J Clin Oncol. 2019 Jun 1;37(16):1424–1431. doi:10.1200/JCO.18.02374. Epub 2019 Apr 23. PMID: 31013172. DavisLE BolejackV RyanCW GanjooKN LoggersET ChawlaS Randomized double-blind phase II study of regorafenib in patients with metastatic osteosarcoma J Clin Oncol 2019 Jun 1 37 16 1424 1431 10.1200/JCO.18.02374 Epub 2019 Apr 23. PMID: 31013172. 779944331013172 Open DOISearch in Google Scholar

[160] Duffaud F, Mir O, Boudou-Rouquette P, Piperno-Neumann S, Penel N, Bompas E, et al., French Sarcoma Group. Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: A non-comparative, randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. 2019 Jan;20(1):120–133. doi:10.1016/S1470-2045(18)30742-3. Epub 2018 Nov 23. PMID: 30477937. DuffaudF MirO Boudou-RouquetteP Piperno-NeumannS PenelN BompasE French Sarcoma Group Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: A non-comparative, randomised, double-blind, placebo-controlled, phase 2 study Lancet Oncol 2019 Jan 20 1 120 133 10.1016/S1470-2045(18)30742-3 Epub 2018 Nov 23. PMID: 30477937. 30477937 Open DOISearch in Google Scholar

[161] Attia A, Bolejack V, Ganjoo KN, George S, Agulnik M, Rushing DA, et al. A phase II trial of regorafenib (REGO) in patients (pts) with advanced Ewing sarcoma and related tumors (EWS) of soft tissue and bone: SARC024 trial results. J Clin Oncol. 2017; 35(15_suppl):11005. AttiaA BolejackV GanjooKN GeorgeS AgulnikM RushingDA A phase II trial of regorafenib (REGO) in patients (pts) with advanced Ewing sarcoma and related tumors (EWS) of soft tissue and bone: SARC024 trial results J Clin Oncol 2017 35 15_suppl 11005 10.1200/JCO.2017.35.15_suppl.11005 Search in Google Scholar

[162] Wang HY, Chu JF, Zhang P, Wang JQ, Yan Z, Yao SN, et al. Safety and efficacy of chemotherapy combined with anlotinib plus anlotinib maintenance in Chinese patients with advanced/metastatic soft tissue sarcoma. Onco Targets Ther. 2020 Feb 19;13:1561–1568. doi:10.2147/OTT.S235349. PMID: 32110053; PMCID: PMC7038775. WangHY ChuJF ZhangP WangJQ YanZ YaoSN Safety and efficacy of chemotherapy combined with anlotinib plus anlotinib maintenance in Chinese patients with advanced/metastatic soft tissue sarcoma Onco Targets Ther 2020 Feb 19 13 1561 1568 10.2147/OTT.S235349 PMID: 32110053; PMCID: PMC7038775. 703877532110053 Open DOISearch in Google Scholar

[163] Xu J, Xie L, Guo W, Tang X, Yang R, Yan T, et al. Anlotinib and irinotecan for advanced Ewing sarcoma after failure of standard therapy: A multicenter, two-cohort, single-arm, open label, phase Ib/II trial (NCT03416517). J Clin Oncol. 2019; 37(15_suppl):11012. XuJ XieL GuoW TangX YangR YanT Anlotinib and irinotecan for advanced Ewing sarcoma after failure of standard therapy: A multicenter, two-cohort, single-arm, open label, phase Ib/II trial (NCT03416517) J Clin Oncol 2019 37 15_suppl 11012 10.1200/JCO.2019.37.15_suppl.11012 Search in Google Scholar

[164] Das SK, Menezes ME, Bhatia S, Wang XY, Emdad L, Sarkar D, Fisher PB. Gene therapies for cancer: Strategies, challenges and successes. J Cell Physiol. 2015 Feb;230(2):259–271. doi:10.1002/jcp.24791. PMID: 25196387; PMCID: PMC4363073. DasSK MenezesME BhatiaS WangXY EmdadL SarkarD FisherPB Gene therapies for cancer: Strategies, challenges and successes J Cell Physiol 2015 Feb 230 2 259 271 10.1002/jcp.24791 PMID: 25196387; PMCID: PMC4363073. 436307325196387 Open DOISearch in Google Scholar

[165] Rao DD, Jay C, Wang Z, Luo X, Kumar P, Eysenbach H, et al. Preclinical justification of pbi-shRNA EWS/FLI1 lipoplex (LPX) treatment for Ewing's sarcoma. Mol Ther. 2016 Aug;24(8):1412–1422. doi:10.1038/mt.2016.93. Epub 2016 May 11. PMID: 27166877; PMCID: PMC5023384. RaoDD JayC WangZ LuoX KumarP EysenbachH Preclinical justification of pbi-shRNA EWS/FLI1 lipoplex (LPX) treatment for Ewing's sarcoma Mol Ther 2016 Aug 24 8 1412 1422 10.1038/mt.2016.93 Epub 2016 May 11. PMID: 27166877; PMCID: PMC5023384. 502338427166877 Open DOISearch in Google Scholar

[166] Brohl AS, Solomon DA, Chang W, Wang J, Song Y, Sindiri S, et al. The genomic landscape of the Ewing sarcoma family of tumors reveals recurrent STAG2 mutation. PLoS Genet. 2014 Jul 10;10(7):e1004475. doi:10.1371/journal.pgen.1004475. Erratum in PLoS Genet. 2014 Aug;10(8):e1004629. PMID: 25010205; PMCID: PMC4091782. BrohlAS SolomonDA ChangW WangJ SongY SindiriS The genomic landscape of the Ewing sarcoma family of tumors reveals recurrent STAG2 mutation PLoS Genet 2014 Jul 10 10 7 e1004475 10.1371/journal.pgen.1004475 Erratum in PLoS Genet. 2014 Aug;10(8):e1004629. PMID: 25010205; PMCID: PMC4091782. 409178225010205 Open DOISearch in Google Scholar

[167] Liu J, Zheng X, Pang X, Li L, Wang J, Yang C, Du G. Ganglioside GD3 synthase (GD3S), a novel cancer drug target. Acta Pharm Sin B. 2018 Sep;8(5):713–720. doi:10.1016/j.apsb.2018.07.009. Epub 2018 Jul 25. PMID: 30245960; PMCID: PMC6147802. LiuJ ZhengX PangX LiL WangJ YangC DuG Ganglioside GD3 synthase (GD3S), a novel cancer drug target Acta Pharm Sin B 2018 Sep 8 5 713 720 10.1016/j.apsb.2018.07.009 Epub 2018 Jul 25. PMID: 30245960; PMCID: PMC6147802. 614780230245960 Open DOISearch in Google Scholar

[168] Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: Results from the phase II KEYNOTE-158 study. J Clin Oncol. 2020 Jan 1;38(1):1–10. doi:10.1200/JCO.19.02105. Epub 2019 Nov 4. PMID: 31682550. MarabelleA LeDT AsciertoPA Di GiacomoAM De Jesus-AcostaA DelordJP Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: Results from the phase II KEYNOTE-158 study J Clin Oncol 2020 Jan 1 38 1 1 10 10.1200/JCO.19.02105 Epub 2019 Nov 4. PMID: 31682550. 818406031682550 Open DOISearch in Google Scholar

[169] Tawbi HA, Burgess M, Bolejack V, Van Tine BA, Schuetze SM, Hu J, et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): A multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017 Nov;18(11):1493–1501. doi:10.1016/S1470-2045(17)30624-1. Epub 2017 Oct 4. Erratum in Lancet Oncol. 2017 Dec;18(12):e711. Erratum in Lancet Oncol. 2018 Jan;19(1):e8. PMID: 28988646. TawbiHA BurgessM BolejackV Van TineBA SchuetzeSM HuJ Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): A multicentre, two-cohort, single-arm, open-label, phase 2 trial Lancet Oncol 2017 Nov 18 11 1493 1501 10.1016/S1470-2045(17)30624-1 Epub 2017 Oct 4. Erratum in Lancet Oncol. 2017 Dec;18(12):e711. Erratum in Lancet Oncol. 2018 Jan;19(1):e8. PMID: 28988646. 793902928988646 Open DOISearch in Google Scholar

[170] Raj S, Bui M, Gonzales R, Letson D, Antonia SJ. Impact of PDL1 expression on clinical outcomes in subtypes of sarcoma. Ann Oncol. 2014;25:iv494–iv510. RajS BuiM GonzalesR LetsonD AntoniaSJ Impact of PDL1 expression on clinical outcomes in subtypes of sarcoma Ann Oncol 2014 25 iv494 iv510 10.1093/annonc/mdu354.10 Search in Google Scholar

[171] Machado I, López-Guerrero JA, Scotlandi K, Picci P, Llombart-Bosch A. Immunohistochemical analysis and prognostic significance of PD-L1, PD-1, and CD8+ tumor-infiltrating lymphocytes in Ewing's sarcoma family of tumors (ESFT). Virchows Arch. 2018 May;472(5):815–824. doi:10.1007/s00428-018-2316-2. Epub 2018 Feb 14. PMID: 29445891. MachadoI López-GuerreroJA ScotlandiK PicciP Llombart-BoschA Immunohistochemical analysis and prognostic significance of PD-L1, PD-1, and CD8+ tumor-infiltrating lymphocytes in Ewing's sarcoma family of tumors (ESFT) Virchows Arch 2018 May 472 5 815 824 10.1007/s00428-018-2316-2 Epub 2018 Feb 14. PMID: 29445891. 29445891 Open DOISearch in Google Scholar

[172] Crompton BD, Stewart C, Taylor-Weiner A, Alexe G, Kurek KC, Calicchio ML, et al. The genomic landscape of pediatric Ewing sarcoma. Cancer Discov. 2014 Nov;4(11):1326–1341. doi:10.1158/2159-8290.CD-13-1037. Epub 2014 Sep 3. PMID: 25186949. CromptonBD StewartC Taylor-WeinerA AlexeG KurekKC CalicchioML The genomic landscape of pediatric Ewing sarcoma Cancer Discov 2014 Nov 4 11 1326 1341 10.1158/2159-8290.CD-13-1037 Epub 2014 Sep 3. PMID: 25186949. 25186949 Open DOISearch in Google Scholar

[173] Tirode F, Surdez D, Ma X, Parker M, Le Deley MC, Bahrami A, et al., St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project and the International Cancer Genome Consortium. Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations. Cancer Discov. 2014 Nov;4(11):1342–1353. doi:10.1158/2159-8290.CD-14-0622. Epub 2014 Sep 15. PMID: 25223734; PMCID: PMC4264969. TirodeF SurdezD MaX ParkerM Le DeleyMC BahramiA St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project and the International Cancer Genome Consortium. Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations Cancer Discov 2014 Nov 4 11 1342 1353 10.1158/2159-8290.CD-14-0622 Epub 2014 Sep 15. PMID: 25223734; PMCID: PMC4264969. 426496925223734 Open DOISearch in Google Scholar

[174] Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. Cancer genome landscapes. Science. 2013 Mar 29;339(6127):1546–1558. doi:10.1126/science.1235122. PMID: 23539594; PMCID: PMC3749880. VogelsteinB PapadopoulosN VelculescuVE ZhouS DiazLAJr KinzlerKW Cancer genome landscapes Science 2013 Mar 29 339 6127 1546 1558 10.1126/science.1235122 PMID: 23539594; PMCID: PMC3749880. 374988023539594 Open DOISearch in Google Scholar

[175] Davis KL, Fox E, Reid JM, Liu X, Minard CG, Weigel B, Mackall, C. ADVL1412: Initial results of a phase I/II study of nivolumab and ipilimumab in pediatric patients with relapsed/refractory solid tumors—A COG study. J Clin Oncol. 2017 35(15_suppl):10526. DavisKL FoxE ReidJM LiuX MinardCG WeigelB MackallC ADVL1412: Initial results of a phase I/II study of nivolumab and ipilimumab in pediatric patients with relapsed/refractory solid tumors—A COG study J Clin Oncol 2017 35 15_suppl 10526 10.1200/JCO.2017.35.15_suppl.10526 Search in Google Scholar

[176] D’Angelo SP, Mahoney MR, Van Tine BA, Atkins J, Milhem MM, Jahagirdar BN, et al. Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): Two open-label, non-comparative, randomised, phase 2 trials. Lancet Oncol. 2018 Mar;19(3):416–426. doi:10.1016/S1470-2045(18)30006-8. Epub 2018 Jan 19. PMID: 29370992; PMCID: PMC6126546. D’AngeloSP MahoneyMR Van TineBA AtkinsJ MilhemMM JahagirdarBN Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): Two open-label, non-comparative, randomised, phase 2 trials Lancet Oncol 2018 Mar 19 3 416 426 10.1016/S1470-2045(18)30006-8 Epub 2018 Jan 19. PMID: 29370992; PMCID: PMC6126546. 612654629370992 Open DOISearch in Google Scholar

[177] Rocchi A, Manara MC, Sciandra M, Zambelli D, Nardi F, Nicoletti G, et al. CD99 inhibits neural differentiation of human Ewing sarcoma cells and thereby contributes to oncogenesis. J Clin Invest. 2010 Mar;120(3):668–680. doi:10.1172/JCI36667. Epub 2010 Feb 8. PMID: 20197622; PMCID: PMC2827943. RocchiA ManaraMC SciandraM ZambelliD NardiF NicolettiG CD99 inhibits neural differentiation of human Ewing sarcoma cells and thereby contributes to oncogenesis J Clin Invest 2010 Mar 120 3 668 680 10.1172/JCI36667 Epub 2010 Feb 8. PMID: 20197622; PMCID: PMC2827943. 282794320197622 Open DOISearch in Google Scholar

[178] O’Neill AF, Dearling JL, Wang Y, Tupper T, Sun Y, Aster JC, et al. Targeted imaging of Ewing sarcoma in preclinical models using a 64Cu-labeled anti-CD99 antibody. Clin Cancer Res. 2014 Feb 1;20(3):678–687. doi:10.1158/1078-0432.CCR-13-1660. Epub 2013 Nov 11. PMID: 24218512; PMCID: PMC3946397. O’NeillAF DearlingJL WangY TupperT SunY AsterJC Targeted imaging of Ewing sarcoma in preclinical models using a 64Cu-labeled anti-CD99 antibody Clin Cancer Res 2014 Feb 1 20 3 678 687 10.1158/1078-0432.CCR-13-1660 Epub 2013 Nov 11. PMID: 24218512; PMCID: PMC3946397. 394639724218512 Open DOISearch in Google Scholar

[179] Dobrenkov K, Ostrovnaya I, Gu J, Cheung IY, Cheung NK. Oncotargets GD2 and GD3 are highly expressed in sarcomas of children, adolescents, and young adults. Pediatr Blood Cancer. 2016 Oct;63(10):1780–1785. doi:10.1002/pbc.26097. Epub 2016 Jun 15. PMID: 27304202; PMCID: PMC5215083. DobrenkovK OstrovnayaI GuJ CheungIY CheungNK Oncotargets GD2 and GD3 are highly expressed in sarcomas of children, adolescents, and young adults Pediatr Blood Cancer 2016 Oct 63 10 1780 1785 10.1002/pbc.26097 Epub 2016 Jun 15. PMID: 27304202; PMCID: PMC5215083. 521508327304202 Open DOISearch in Google Scholar

[180] Kailayangiri S, Altvater B, Meltzer J, Pscherer S, Luecke A, Dierkes C, et al. The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting. Br J Cancer. 2012 Mar 13;106(6):1123–1133. doi:10.1038/bjc.2012.57. Epub 2012 Feb 28. PMID: 22374462; PMCID: PMC3304425. KailayangiriS AltvaterB MeltzerJ PschererS LueckeA DierkesC The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting Br J Cancer 2012 Mar 13 106 6 1123 1133 10.1038/bjc.2012.57 Epub 2012 Feb 28. PMID: 22374462; PMCID: PMC3304425. 330442522374462 Open DOISearch in Google Scholar

[181] Fisher JP, Flutter B, Wesemann F, Frosch J, Rossig C, Gustafsson K, Anderson J. Effective combination treatment of GD2-expressing neuroblastoma and Ewing's sarcoma using anti-GD2 ch14.18/CHO antibody with Vγ9Vδ2+ γδT cells. Oncoimmunology. 2015 Apr 27;5(1):e1025194. doi:10.1080/2162402X.2015.1025194. PMID: 26942051; PMCID: PMC4760299. FisherJP FlutterB WesemannF FroschJ RossigC GustafssonK AndersonJ Effective combination treatment of GD2-expressing neuroblastoma and Ewing's sarcoma using anti-GD2 ch14.18/CHO antibody with Vγ9Vδ2+ γδT cells Oncoimmunology 2015 Apr 27 5 1 e1025194 10.1080/2162402X.2015.1025194 PMID: 26942051; PMCID: PMC4760299. 476029926942051 Open DOISearch in Google Scholar

[182] Lipinski M, Hirsch MR, Deagostini-Bazin H, Yamada O, Tursz T, Goridis C. Characterization of neural cell adhesion molecules (NCAM) expressed by Ewing and neuroblastoma cell lines. Int J Cancer. 1987 Jul 15;40(1):81–86. doi:10.1002/ijc.2910400115. PMID: 3036723. LipinskiM HirschMR Deagostini-BazinH YamadaO TurszT GoridisC Characterization of neural cell adhesion molecules (NCAM) expressed by Ewing and neuroblastoma cell lines Int J Cancer 1987 Jul 15 40 1 81 86 10.1002/ijc.2910400115 PMID: 3036723. 3036723 Open DOISearch in Google Scholar

[183] Kailayangiri S, Altvater B, Meltzer J, Pscherer S, Luecke A, Dierkes C, et al. The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting. Br J Cancer. 2012 Mar 13;106(6):1123–1133. doi:10.1038/bjc.2012.57. Epub 2012 Feb 28. PMID: 22374462; PMCID: PMC3304425. KailayangiriS AltvaterB MeltzerJ PschererS LueckeA DierkesC The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting Br J Cancer 2012 Mar 13 106 6 1123 1133 10.1038/bjc.2012.57 Epub 2012 Feb 28. PMID: 22374462; PMCID: PMC3304425. Open DOISearch in Google Scholar

[184] Ghisoli M, Barve M, Mennel R, Lenarsky C, Horvath S, Wallraven G, et al. Three-year follow up of GMCSF/bi-shRNA(furin) DNA-transfected autologous tumor immunotherapy (Vigil) in metastatic advanced Ewing's sarcoma. Mol Ther. 2016 Aug;24(8):1478–1483. doi:10.1038/mt.2016.86. Epub 2016 Apr 25. PMID: 27109631; PMCID: PMC5023386. GhisoliM BarveM MennelR LenarskyC HorvathS WallravenG Three-year follow up of GMCSF/bi-shRNA(furin) DNA-transfected autologous tumor immunotherapy (Vigil) in metastatic advanced Ewing's sarcoma Mol Ther 2016 Aug 24 8 1478 1483 10.1038/mt.2016.86 Epub 2016 Apr 25. PMID: 27109631; PMCID: PMC5023386. 502338627109631 Open DOISearch in Google Scholar