Signaling pathway ‘key needle within the haystack’ driving Barrett’s, esophageal cancer
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Researchers have identified a cell signaling pathway involved in the development of Barrett’s esophagus and esophageal adenocarcinoma, which may lead to possible life-saving therapy for this aggressive cancer.
In a study published in Gastroenterology, Kishore Guda, DVM, PhD, associate professor at Case Western Reserve University School of Medicine and Case Comprehensive Cancer Center, and colleagues performed whole transcriptome RNA sequencing in primary Barrett’s esophagus (BE), esophageal adenocarcinoma (EAC), normal esophageal squamous and gastric biopsy tissues and found that EphB2 signaling was hyperactivated in most cases of EAC and BE.
“What was rather surprising, or intriguing, was that we found EphB2 to regulate some of the major molecular networks that play central roles in digestive tract health and disease, including its regulation of a key cancer gene, c-MYC,” Guda told Healio.
The EphB2 pathway also was frequently activated in gastric cancers, he said. “Both these cancer types are highly heterogeneous, aggressive and refractory to standard-of-care treatments, with lack of effective targeted therapies and poorer survival rates.”
This discovery, he continued, could potentially lead to EphB2-targeted therapeutics for these and other cancers. “The widely known immune checkpoint therapies have also proven not effective for the vast majority of these cancers and solid tumors in general,” Guda said. “We are, therefore, currently developing a novel immune cell-based therapy to specifically target these cancers expressing EphB2.”
According to Guda, these study findings mark the first step toward improving outcomes for patients with EAC, which has a “dismal” 5-year survival rate.
“Targeting EphB2 in gastroesophageal cancers hasn’t been tried before,” he said. “If our preclinical studies prove effective, future clinical trials can include immune cell approaches and other strategies, including antibodies and chemical inhibitors, targeting EphB2 pathway alone or in combination with standard-of-care treatment options in a primary or metastatic setting.”
Of particular note, Guda said, is that identification of the EphB2 signaling pathway was made possible through multidisciplinary research.
“For this study, we performed integrative analyses using patient tissue biopsies, systems biology, mathematical modeling, and animal and wet-lab studies to identify this key needle within the haystack,” he said.
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