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Study: Possible new druggable target in Ewing's Sarcoma
Date:1/22/2014

Ewing's Sarcoma is an aggressive pediatric cancer, most commonly caused by the improper fusion of the gene EWS with the gene FLI1. Though the cause has long been known, therapeutic targeting of this fusion has to date proven very difficult. A University of Colorado Cancer Center study, recently published in the journal Oncogene, looked downstream from this fusion to discover other links in the chain of events that leads to cancer this fusion puts in motion microRNA-22, which regulates another gene, KDM3A, and this signaling chain helps ensure that the outcome of the EWS/FLI1 fusion is cancer. Researchers suggest that these new targets may provide more easily druggable alternatives to the EWS/FLI1 fusion itself.

"We started with all the microRNAs downstream from the EWS/FLI1 fusion and narrowed in on microRNA-22. But then we looked even further downstream from there and found that microRNA-22 works through another gene, KDM3A, to cause this cancer. When we turned down this gene (KDM3A) in lab studies, we observed a profound inhibition of the tumorigenic properties of Ewing Sarcoma cells," says Paul Jedlicka, MD, PhD, CU Cancer Center investigator and assistant professor of pathology at the University of Colorado School of Medicine.

This study highlights the complex cascade of events that cause cancer. Even in seemingly "simple" cancers like Ewing Sarcoma with known oncogenic drivers, cancer-causing action tends to depend on a cascade of events the oncogenes initiate. In other words, oncogenes may sit at the head of long, complex strings of cellular events, all of which are needed to cause cancer.

Likewise, genes aren't the only level at which this string of events can be interrupted between a gene and its expression as a (potentially dangerous) protein lies all the mechanics of transcription, including the involvement of chemicals that transport a gene's information to the machinery that makes proteins (RNA), and chemicals tha
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Contact: Garth Sundem
garth.sundem@ucdenver.edu
University of Colorado Denver
Source:Eurekalert

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