A team of researchers believe they have identified a cell-signaling pathway responsible for the development of esophageal adenocarcinomas, an aggressive type of esophageal cancer that has gradually become more common, even in younger people. Research published by Venkitachalam et al in Gastroenterology explained how the Ephrin B2 (EphB2) tyrosine kinase pathway is activated during the development of esophageal adenocarcinomas and contributes to cancer growth. In addition, the findings show that the EphB2 pathway appears to control the growth of cancer cells while also regulating the behavior of normal esophageal cells.
“The incidence of esophageal cancers has increased several-fold over the last few decades, making it the most common esophageal malignancy in the United States,” said Kishore Guda, DVM, PhD, Associate Professor at the Case Western Reserve University School of Medicine and member of the Case Comprehensive Cancer Center. “Like gastric and pancreatic cancers, these are highly aggressive malignancies that can be resistant to treatment, with dismal survival rates and with lack of effective targeted therapies.”
“From a molecular standpoint, EphB2 induces the levels of a well-recognized procancer gene called c-MYC. One mechanism by which EphB2 seems to affect MYC levels is through its direct interaction with a protein known as MYCBP2, which is a suppressor of MYC activity,” Dr. Guda said. “This is the first discovery to our knowledge that demonstrates EphB2 regulation of MYC and its physical interaction with MYCBP2.”
By analyzing normal, precancer, and cancerous biopsy samples with RNA sequencing, the researchers found that EphB2 signaling is hyperactivated in nearly all instances of esophageal adenocarcinomas, as well as in Barrett’s esophagus.
The scientists believe the EphB2 pathway is an attractive therapeutic target and suppressing its activity in cancer could be a beneficial treatment strategy for these cancers.
“Our immediate goal is to explore and develop EphB2 chemical inhibitors and/or EphB2-targeting immune-cell based strategies, and to test their efficacy in preclinical esophageal as well as gastric cancer models, followed by transitioning to human trials,” said Dr. Guda.
Disclosure: For full disclosures of the study authors, visit gastrojournal.org.
