Clin Pediatr Hematol Oncol.  2012 Apr;19(1):17-25.

Recent Advances in the Molecular Mechanisms and Therapeutic Strategies Targeting EWS/ETS in Ewing Sarcoma Family of Tumors

Affiliations
  • 1Department of Pediatrics, Graduate School of Medicine, Gachon University, Incheon, Korea. isjeon@gilhospital.com

Abstract

Most cases of Ewing sarcoma family of tumors (ESFT) display a characteristic chromosomal translocation resulting in the formation of the chimeric gene, EWS/ETS. During the past two decades, the understanding of the molecular biology of the EWS/ETS gene and its role in ESFT cases has increased remarkably, and has led to the development of new therapeutic strategies. EWS/ETS is a transcription factor composed of the EWS transactivation domain and the ETS DNA binding domain. The resulting de novo chimera, EWS/ETS, disturbs the transcription of target genes. Initially known to activate its target genes, EWS/ETS has been found to represses their transcription as well. The aberrant regulation of the transcription of this gene contributes to the cellular transformation, growth, proliferation and metastasis of ESFT. Additionally, the disordered EWS/ETS protein interacts with other protein partners in transcription or splicing, and these abnormal interactions could affect gene transcription and splicing related to ESFT formation. However, the molecular mechanism underlying the oncogenesis of EWS/ETS in ESFT cases is complex and requires additional research in order to clarify its underlying mechanisms. Drugs that target the molecular mechanisms of EWS/ETS in the manifestation of ESFT have been developed and clinical studies using these drugs have recently been performed. Encouraging results were reported and new therapies may be available for use in the near future.

Keyword

Ewing sarcoma; EWS/ETS; Transcription

MeSH Terms

Cell Transformation, Neoplastic
Chimera
DNA
Humans
Molecular Biology
Neoplasm Metastasis
Sarcoma, Ewing
Transcription Factors
Transcriptional Activation
Translocation, Genetic
DNA
Transcription Factors
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