Polyamine Depletion by D,L-α-Difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis
DFMO slows the growth of Ewing sarcoma cells in vitro, with a profound impact on sphere formation and clonogenic growth, and affects all aspects of Ewing sarcoma tumorigenesis, including tumor initiation, tumor growth, and metastasis, probably through induction of ferroptosis mediated by polyamine depletion. Our results provide preclinical justification to test the ability of DFMO to prevent metastatic recurrence in patients with Ewing sarcoma.
Authors
- Kyle W. Jackson (ORCID: https://orcid.org/0000-0002-3398-7548)
- Patrick Cahan (ORCID: https://orcid.org/0000-0003-3652-2540)
- Rachel Offenbacher (ORCID: https://orcid.org/0000-0002-5211-6457)
- Da Peng (ORCID: https://orcid.org/0000-0001-5782-8405)
- Paul Ciero (ORCID: https://orcid.org/0009-0000-5199-9270)
- Jinghang Zhang (ORCID: https://orcid.org/0000-0003-1436-6460)
- David M. Loeb (ORCID: https://orcid.org/0000-0002-7319-5000)
- Yuqi Tan (ORCID: https://orcid.org/0000-0002-7200-3222)
- Masanori Hayashi (ORCID: https://orcid.org/0000-0002-9508-0159)
- Tracy Murray Stewart (ORCID: https://orcid.org/0000-0001-8679-6414)
- Robert A. Casero (ORCID: https://orcid.org/0000-0001-5653-3306)
- Jackson R. Foley (ORCID: https://orcid.org/0000-0002-4383-9522)
Institutions
- Albert Einstein College of Medicine (US)
- Johns Hopkins University (US)
- Palo Alto University (US)
- Johns Hopkins Medicine (US)
- Johns Hopkins Hospital (US)
- Sidney Kimmel Comprehensive Cancer Center (US)
- Indiana University School of Medicine
- University of Colorado Anschutz Medical Campus (US)
- Indiana University – Purdue University Indianapolis (US)
- University of Colorado Denver (US)
- Stanford University (US)
Publication Details
- Journal
- Clinical Cancer Research
- Published
- 2025-07-24
- DOI
- https://doi.org/10.1158/1078-0432.ccr-24-1778
- Citations
- 3
- Primary Topic
- Sarcoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 4.56
Funders
- National Institutes of Health
- Albert Einstein College of Medicine, Yeshiva University
- National Cancer Institute
- National Institute of General Medical Sciences