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Positive Preclinical Results for Smo Inhibitor in Esophageal CA

Last Updated: December 26, 2012.

 

Blockade of Hh pathway cuts risk of Barrett's esophagus, esophageal cancer in rat study

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In rats with induced gastroduodenoesophageal reflux, a small molecular inhibitor of smoothened can reduce the risk of developing Barrett's esophagus and esophageal adenocarcinoma, according to a study published online Oct. 26 in the Annals of Surgery.

WEDNESDAY, Dec. 26 (HealthDay News) -- In rats with induced gastroduodenoesophageal reflux, a small molecular inhibitor of smoothened (Smo) can reduce the risk of developing Barrett's esophagus and esophageal adenocarcinoma, according to a study published online Oct. 26 in the Annals of Surgery.

Noting that activated hedgehog (Hh) pathway correlates with development of Barrett's esophagus and esophageal adenocarcinoma, Michael K. Gibson, M.D., Ph.D., from the University of Pittsburgh, and colleagues examined whether blocking the Hh pathway with the Smo inhibitor could block the development of Barrett's esophagus and esophageal adenocarcinoma in rats with induced gastroduodenoesophageal reflux.

The researchers found that, compared with normal esophageal tissue, mRNA Hh expression was 184 times higher in Barrett's esophagus and 99 times higher in esophageal adenocarcinoma. After 28 weeks, rats treated with an oral Smo inhibitor had relative risk reductions of 36 percent for Barrett's esophagus and 62 percent for esophageal adenocarcinoma. Ki-67 was downregulated in treated versus untreated esophageal adenocarcinoma but there was no difference in cleaved caspase-3.

"In conclusion, we demonstrated that the activated Hh pathway may play an important role in the development of Barrett esophagus and esophageal adenocarcinoma, and the Smo inhibitor has the potential to prevent the development of Barrett esophagus and esophageal adenocarcinoma in the preclinical setting," Gibson and colleagues write. "These preliminary results support the need for a detailed downstream evaluation of the Hh pathway in this model so that we may definitively prove the preventative effect of Smo inhibition and understand the precise mechanism of action."

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Copyright © 2012 HealthDay. All rights reserved.


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