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Updated: Sep 27, 2025

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
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Published on: June 27, 2020

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Inhibitor of DNA binding 2 (ID2) regulates the expression of developmental genes and tumorigenesis in ewing sarcoma

Stacia L Koppenhafer1, Kelli L Goss1, Ellen Voigt2

  • 1Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Iowa, Iowa City, IA, 52242, USA.

Oncogene
|April 15, 2022
PubMed

Insights

Inhibitor of DNA Binding 2 (ID2) regulates Ewing sarcoma growth. The FDA-approved drug homoharringtonine targets ID2 and related proteins, offering a potential new therapy for sarcomas.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Sarcomas present significant therapeutic challenges due to limited treatment advancements and severe side effects.
  • Current sarcoma treatment regimens have seen minimal progress over the last two decades.
  • Differentiation-based therapies, while used for other cancers, have faced difficulties in application to sarcomas.

Purpose of the Study:

  • To investigate the role of Inhibitor of DNA Binding 2 (ID2) in Ewing sarcoma development and growth.
  • To explore the therapeutic potential of homoharringtonine in targeting ID2 and related proteins in Ewing sarcoma.

Main Methods:

  • Utilized CRISPR-mediated gene knockout to assess ID2 function in vitro and in vivo.
  • Administered homoharringtonine to an Ewing sarcoma xenograft mouse model.
  • Analyzed protein levels of ID1, ID2, and ID3 family members.

Main Results:

  • ID2 was identified as a critical regulator of developmental genes and tumor growth in Ewing sarcoma.
  • Homoharringtonine significantly reduced tumor growth and improved survival in a mouse model.
  • Homoharringtonine decreased protein levels of ID1, ID2, and ID3 in cancer cells.

Conclusions:

  • ID2 plays a crucial role in the developmental regulation and proliferation of Ewing sarcoma.
  • Homoharringtonine demonstrates potential as a novel therapeutic agent for sarcomas by targeting the ID protein family.
  • This study identifies a promising therapeutic strategy using an FDA-approved drug for difficult-to-treat sarcomas.

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