Targeted Therapy for EWS-FLI1 in Ewing Sarcoma

被引：7
|
作者：
Gong, Helong [1 ]
Xue, Busheng [2 ]
Ru, Jinlong [3 ]
Pei, Guoqing [4 ]
Li, Yan [1 ]
机构：
[1] China Med Univ, Shengjing Hosp, Dept Orthopaed Surg, 36 Sanhao St, Shenyang 110004, Peoples R China
[2] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Hematol, Xian 710061, Peoples R China
[3] Helmholtz Ctr Munich, German Res Ctr Environm Hlth, Inst Virol, Neuherberg, Germany
[4] Air Force Med Univ, Xijing Hosp, Dept Orthoped, Xian 710032, Peoples R China
来源：
CANCERS | 2023年 / 15卷 / 16期
关键词：
ewing sarcoma; EWS-FLI1; protein complex; targeted therapy; immunotherapy; 6-TRANSMEMBRANE EPITHELIAL ANTIGEN; DIRECT TRANSCRIPTIONAL TARGET; FUSION PROTEIN; TUMOR-GROWTH; IN-VITRO; T-CELLS; HISTONE DEACETYLASE; EWSR1-FLI1; ACTIVITY; GENOMIC LANDSCAPE; BINDING PROTEIN;
D O I：
10.3390/cancers15164035
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Ewing sarcoma (EwS) is a rare and predominantly pediatric malignancy of bone and soft tissue in children and adolescents. Although international collaborations have greatly improved the prognosis of most EwS, the occurrence of macrometastases or relapse remains challenging. The prototypic oncogene EWS-FLI1 acts as an aberrant transcription factor that drives the cellular transformation of EwS. In addition to its involvement in RNA splicing and the DNA damage response, this chimeric protein directly binds to GGAA repeats, thereby modifying the transcriptional profile of EwS. Direct pharmacological targeting of EWS-FLI1 is difficult because of its intrinsically disordered structure. However, targeting the EWS-FLI1 protein complex or downstream pathways provides additional therapeutic options. This review describes the EWS-FLI1 protein partners and downstream pathways, as well as the related target therapies for the treatment of EwS.
引用
收藏
页数：21
相关论文
共 50 条
  • [31] USP19 deubiquitinates EWS-FLI1 to regulate Ewing sarcoma growth
    Gierisch, Maria E.
    Pedot, Gloria
    Walser, Franziska
    Lopez-Garcia, Laura A.
    Jaaks, Patricia
    Niggli, Felix K.
    Schafer, Beat W.
    SCIENTIFIC REPORTS, 2019, 9 (1)
  • [32] USP19 deubiquitinates EWS-FLI1 to regulate Ewing sarcoma growth
    Maria E. Gierisch
    Gloria Pedot
    Franziska Walser
    Laura A. Lopez-Garcia
    Patricia Jaaks
    Felix K. Niggli
    Beat W. Schäfer
    Scientific Reports, 9
  • [33] EWS-FLI1 target genes recovered from Ewing's sarcoma chromatin
    Siligan, C
    Ban, J
    Bachmaier, R
    Spahn, L
    Kreppel, M
    Schaefer, KL
    Poremba, C
    Aryee, DNT
    Kovar, H
    ONCOGENE, 2005, 24 (15) : 2512 - 2524
  • [34] Identification and characterization of EWS-FLI1 binding partners in Ewing sarcoma cell lines
    Rotondi, Matthew L.
    Houghton, Peter J.
    CANCER RESEARCH, 2017, 77
  • [35] EWS-FLI1 target genes recovered from Ewing's sarcoma chromatin
    Christine Siligan
    Jozef Ban
    Radostina Bachmaier
    Laura Spahn
    Michael Kreppel
    Karl-Ludwig Schaefer
    Christopher Poremba
    Dave N T Aryee
    Heinrich Kovar
    Oncogene, 2005, 24 : 2512 - 2524
  • [36] Protein stability screen to identify compounds destabilizing EWS-FLI1 in Ewing sarcoma
    Pedot, Gloria
    Niggli, Felix K.
    Schaefer, Beat W.
    CANCER RESEARCH, 2019, 79 (13)
  • [37] EWS-FLI1 confers exquisite sensitivity to NAMPT inhibition in Ewing sarcoma cells
    Mutz, Cornelia N.
    Schwentner, Raphaela
    Aryee, Dave N. T.
    Bouchard, Eric D. J.
    Mejia, Edgard M.
    Hatch, Grant M.
    Kauer, Maximilian O.
    Katschnig, Anna M.
    Ban, Jozef
    Garten, Antje
    Alonso, Javier
    Banerji, Versha
    Kovar, Heinrich
    ONCOTARGET, 2017, 8 (15) : 24679 - 24693
  • [38] Lurbinectedin Inactivates the Ewing Sarcoma Oncoprotein EWS-FLI1 by Redistributing It within the Nucleus
    Harlow, Matt L.
    Maloney, Nichole
    Roland, Joseph
    Navarro, Maria Jose Guillen
    Easton, MatthewK.
    Kitchen-Goosen, Susan M.
    Boguslawski, Elissa A.
    Madaj, Zachary B.
    Johnson, Ben K.
    Bowman, Megan J.
    D'Incalci, Maurizio
    Winn, Mary E.
    Turner, Lisa
    Hostetter, Galen
    Galmarini, Carlos Mara
    Aviles, Pablo M.
    Grohar, Patrick J.
    CANCER RESEARCH, 2016, 76 (22) : 6657 - 6668
  • [39] Inhibiting EWS-FLI1 function by targeting GGAA microsatellites in Ewing sarcoma cells
    Lai, Xiaoyi
    Kida, Yuki
    Takatori, Atsushi
    CANCER SCIENCE, 2024, 115 : 1897 - 1897
  • [40] EWS-FLI1 and Menin Converge to Regulate ATF4 Activity in Ewing Sarcoma
    Jimenez, Jennifer A.
    Apfelbaum, April A.
    Hawkins, Allegra G.
    Svoboda, Laurie K.
    Kumar, Abhijay
    Ruiz, Ramon Ocadiz
    Garcia, Alessandra X.
    Haarer, Elena
    Nwosu, Zeribe C.
    Bradin, Joshua
    Purohit, Trupta
    Chen, Dong
    Cierpicki, Tomasz
    Grembecka, Jolanta
    Lyssiotis, Costas A.
    Lawlor, Elizabeth R.
    MOLECULAR CANCER RESEARCH, 2021, 19 (07) : 1182 - 1195
12345