Home Career Researchers suggest pathway as potential therapeutic target for gastroesophageal cancer – ScienceDaily

Researchers suggest pathway as potential therapeutic target for gastroesophageal cancer – ScienceDaily


Of the approximately 20,000 people in the U.S. diagnosed with esophageal cancer this year, only 4,000 are likely to be alive in 2027.

Such gruesome data have long led researchers to try to understand the roots of the disease, but they have found little – until now.

A team of researchers from Case Western Reserve University School of Medicine and Case Comprehensive Cancer Center believe they have identified a cellular signaling pathway responsible for the development of esophageal adenocarcinoma, an aggressive form of esophageal cancer that is gradually becoming more common, even in young adults. people.

“The incidence of esophageal cancer has increased severalfold over the past several decades, making it the most common esophageal malignancy in the United States,” said Kishore Hooda, an associate professor at the School of Medicine and member of the Center for Comprehensive Cancer Care. “Like gastric and pancreatic cancers, these are highly aggressive malignancies that can be resistant to treatment, with appalling survival rates and a lack of effective targeted therapies.”

A new study published this month in the Gastroenterologyexplains how an important molecular signal known to scientists as the “Ephrin B2 (EphB2) tyrosine kinase pathway” is activated during the development of esophageal adenocarcinoma and promotes cancer growth. The findings also show that the EphB2 pathway appears to control the growth of cancer cells while regulating the behavior of normal esophageal cells.

“From a molecular perspective, EphB2 induces the level of a well-known pro-cancer gene called c-MYC. One of the mechanisms by which EphB2 appears to affect MYC levels is through its direct interaction with a protein known as MYCBP2, which is a suppressor of MYC activity,” Guda said. “This is the first discovery, to our knowledge, that demonstrates MYC regulation by EphB2 and its physical interaction with MYCBP2.”

By analyzing normal, precancerous and cancerous biopsy samples with RNA sequencing, the researchers found that EphB2 signaling is hyperactivated in almost all cases of esophageal adenocarcinoma, as well as in a disease called Barrett’s esophagus.

Barrett’s esophagus occurs when the lining of the esophagus is damaged by acid reflux, causing the cells in the esophagus to be replaced by intestinal-type cells. According to the National Institutes of Health (NIH), this condition is associated with an increased risk of esophageal cancer.

Scientists believe that the EphB2 pathway is an attractive therapeutic target, and suppressing its activity in cancer may be a useful strategy for treating these cancers.

“Our immediate goal is to study and develop chemical inhibitors of EphB2 and/or immune cell-based strategies targeting EphB2, and to test their efficacy in preclinical models of esophageal and gastric cancer, and then move to human trials,” Guda said. .

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Materials is provided Case Western Reserve University. Note: Content can be edited for style and length.

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