Signature-Based Small Molecule Screening Identifies Cytosine Arabinoside as an EWS/FLI Modulator in Ewing Sarcoma
2007

Cytosine Arabinoside as a Modulator in Ewing Sarcoma

publication Evidence: moderate

Author Information

Author(s): Kimberly Stegmaier, Jenny S. Wong, Kenneth N. Ross, Kwan T. Chow, David Peck, Renee D. Wright, Stephen L. Lessnick, Andrew L. Kung, Todd R. Golub

Primary Institution: Dana-Farber Cancer Institute and Children's Hospital Boston, Harvard Medical School

Hypothesis

Screening small-molecule libraries highly enriched for FDA-approved drugs will provide a more rapid path to clinical application for Ewing sarcoma treatment.

Conclusion

The study identifies cytosine arabinoside (ARA-C) as a potent modulator of the EWS/FLI oncoprotein in Ewing sarcoma, warranting clinical trials.

Supporting Evidence

  • ARA-C reduced EWS/FLI protein abundance and diminished cell viability.
  • ARA-C abrogated tumor growth in a xenograft model.
  • Clinical trials testing ARA-C are warranted due to its safety profile.

Takeaway

Researchers found that a drug called ARA-C can help treat a type of cancer called Ewing sarcoma by targeting a specific protein that helps the cancer grow.

Methodology

A gene expression signature for the EWS/FLI off state was determined using microarray profiling, followed by screening a small-molecule library enriched for FDA-approved drugs.

Limitations

The study primarily focuses on in vitro and xenograft models, which may not fully replicate human responses.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pmed.0040122

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