New signalling pathway driving Barrett’s esophagus and esophageal cancer identified

September 2022 Science Willem van Altena

Researchers at Case Western Reserve University School of Medicine and Case Comprehensive Cancer center in Cleveland (USA) have identified hyper activation of a key signalling pathway in the development of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). The findings of this study were recently published in the journal Gastroenterology.

Both BE and EAC are highly aggressive and heterogeneous pre-cancerous and cancerous conditions and often result in poorer clinical outcomes with available standard of care. Therefore, new and focussed treatment options are needed to improve current survival rates. Towards this, the researchers sequenced the transcriptome (total RNA) of tumor biopsies of EC, EAC, normal esophageal squamous and gastric cancers. Further, they performed a integrated expression analysis using systems biology, mathematical modelling and complemented it with wet-lab and animal studies.

Key oncogene

The integrated analysis found that EphB2 signalling was hyper activated in most cases of BE and EAC. The significance of these findings is reflected in the fact that EphB2 regulates major regulatory networks regulating digestive tract including the key oncogene, c-MYC.

Highly significant

This discovery is highly significant for developing new treatments for these patients with dismal 5-year survival rates. As the current immune checkpoint inhibitors are ineffective for majority of these cancers, the researchers are developing novel immune-therapy for targeting cancer cells expressing EphB2.

The study’s lead, Kishore Guda said, “Targeting EphB2 in gastroesophageal cancers hasn’t been tried before. 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.”

Reference

Venkitachalam S, Babu D, Ravillah D, et al. The Ephrin B2 Receptor Tyrosine Kinase Is a Regulator of Proto-oncogene MYC and Molecular Programs Central to Barrett’s Neoplasia. Gastroenterology. 2022 Jul

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