Of the few 20 000 people in the United States diagnosed with most esophageal cancers this year, only 4 000 are likely to still be alive in 2027.
These dire data have long prompted researchers to try to understand the roots of the disease, but they have found little, until ‘now.
A team of researchers from Circumstance Western Reserve College University of Drugs and the Situation Extensive Cancer Center believe they have identified a cell signaling pathway responsible for the development of adenocarcinomas of esophagus, an aggressive form of esophageal cancer that has gradually become more common, even in younger people. people.
“The incidence of esophageal cancers has increased several-fold over the past few decades, making it the most common esophageal malignancy in the States States,” said Kishore Guda, an associate professor at the medical school and a member of the Situation In Depth Cancer Heart. “Like gastric and pancreatic cancers, they are very aggressive malignancies that can be resistant to treatment, with dismal survival rates and with a lack of effective targeted therapies.”
New research published this month in Gastroenterology explains how a vital molecular signal, known to scientists as the “Ephrin B2 (EphB2) Tyrosine kinase pathway,” is activated during the development of esophageal adenocarcinomas and contributes to the growth of the most cancers. The results also show that the EphB2 pathway appears to control cancer cell growth while regulating the behavior of normal esophageal cells.
“From a molecular perspective, EphB2 induces the levels of a well-known pro-cancer gene called c-MYC. One mechanism 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 finding to our knowledge that demonstrates EphB2 regulation of MYC and its physical conversation with MYCBP2.”
By analyzing normal, precancerous, and cancer with RNA sequencing, researchers have found that EphB2 signaling is hyperactivated in almost all cases of esophageal adenocarcinomas as well as in a condition called Barrett’s esophagus.
Barrett’s esophagus occurs when the lining of the esophagus is damaged by acid reflux, resulting in the replacement of esophageal cells with gut-like cells . This condition is linked to an increased risk of developing esophageal cancer, according to the Nationwide Institutes of Overall health (NIH).
Scientists believe that the EphB2 pathway is a interesting therapeutic target and that the suppression of its activity in cancer could be a beneficial treatment strategy for these cancers.
“Our immediate objective is to explore and develop inhibitors chemicals of EphB2 and/or immune cell-based strategies targeting EphB2, and to test their efficacy in preclinical models of most esophageal and gastric cancers, followed by a transition to clinical trials. man,” Guda said.