On March 17, 2025 Tract Bio, a biotechnology company discovering and developing novel therapies for cancer and inflammatory disease, reported the publication of preclinical research in Gastroenterology (Press release, Tract Bio, MAR 17, 2025, View Source [SID1234651199]). The article, "Evolution of Esophageal Adenocarcinoma from Precursor Lesion Stem Cells" describes results from a preclinical study applying the Company’s proprietary stemECHO epithelial stem cell cloning technology, where regenerative stem cells were cloned from epithelial tissues to analyze the evolution of esophageal adenocarcinoma (EAC) and identify potential therapeutic targets and drug combinations.
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In the study, each of the precursor lesions in the evolution of EAC, including Barrett’s esophagus (BE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD), were shown to possess discrete populations of clonogenic cells that are potential therapeutic targets. DNA sequencing of these clones revealed intralesional heterogeneity and clonal resolution of the mutation progression in patients with BE, LGD, HGD, and EAC. High-throughput chemical screens against BE stem cells reveal drug combinations that are similarly effective against stem cells of LDG, HGD, and EAC. Synthetic lethal combinations were then developed that appear effective against BE, LGD, HGD, and EAC, both in vitro and in vivo, while simultaneously promoting normal esophageal stem cells.
"EAC, as with all metastatic cancers, is the result of an evolutionary process which is dominated by a succession of precursor lesions," said Frank McKeon, Ph.D., Interim Chief Scientific Officer of Tract Bio. "In this study, our unique and proprietary epithelial stem cell cloning platform, stemECHO, allowed us to clone epithelial stem cells while preserving their genetic integrity, enabling the discovery of the underlying mechanism. By maintaining the genetic consistency of the cloned cells, we are able to study disease mechanisms with unprecedented precision, opening the door to new diagnostic tools and therapies. We look forward to continuing this important work."
"The clonogenic cells in each of the regenerative lesions described in this paper, BE, LGD, HGD and EAC, each display functional properties of stem cells. Given the role of stem cells of normal epithelia in the regenerative growth of these tissues, the lesional stem cells could represent important therapeutic targets within tumors," said Richard Russell, Chief Executive Officer of Tract Bio. "Toward this end, our synthetic lethal strategies identified highly effective drug combinations against BE stem cells that showed similar efficacy against stem cells from each lesion in the progression to EAC and EAC itself. Based on these findings, we expect that the continued development of these drug combinations may lead to clinically effective treatments to prevent or treat EAC and perhaps other epithelial cancers by targeting the root causes of these conditions."