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Scientists find molecular pathway suspected in precancerous stomach lesions

BOSTON--Researchers at Dana-Farber Cancer Institute have identified a chain of molecular signals that generate the specialized lining of the stomach during fetal development a discovery that could lead to better diagnosis, treatment and prevention of stomach and esophageal cancer in adults.

Damage to the stomach lining, such as from acid reflux or helicobacter pylori (H. pylori) infections, might reactivate the newly found signaling pathway but in this situation it would work in the opposite direction. As a result, the lining reverts to a more generic intestinal type of cells that form cancer-prone lesions.

Ramesh Shivdasani, MD, PhD, of Dana-Farber, senior author of a report in the April 4 issue of Developmental Cell, said the finding "opens a window that could help us eventually interfere with these pathways when they become abnormal. It should give us a list of potential therapeutic targets and could even help us to prevent the development of the precancerous lesions."

The lead author is Byeong-Moo Kim, PhD, also of Dana-Farber.

Patients with the increasingly common disorder known as Gastroesophageal Reflux Disease, or GERD, are at risk of developing precancerous lesions in the upper end of the stomach or the adjoining lower end of the esophagus. These lesions require intense frequent monitoring by endoscopy and sometimes prophylactic surgery to decrease the threat of this dangerous form of cancer. Cancer of the "gastroesophageal junction" has increased dramatically in the past two decades, especially in patients younger than 40 years.

Shivdasani's laboratory studies the "rules" according to which body tissues develop their distinctive form and function at the beginning of life, because they may be reactivated, abnormally, when cancer arises later.

"Cancers of the stomach are almost always preceded by the conversion of the stomach type of lining to an intestinal type," says Shivdasani. In the developing f
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Contact: Bill Schaller or Richard Saltus
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
4-Apr-2005


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