New Insights into Origin of Stomach Cancer

Researchers anticipated that the identification of stem cells will enable drug discovery to pre-empt cancers of the stomach and esophagus at their origin site.

Cancers of the stomach and esophagus - esophageal adenocarcinoma (EAC) which originate from different regions of the gastrointestinal tract, have identical precursor stem cells.

“These ‘origin’ cells are present in all normal individuals, and yet somehow are unusually susceptible to mutational changes that start them down the path to precursor lesions for highly lethal cancers,” said Frank McKeon, professor of biology and biochemistry and director of the Somatic Stem Cell Center at UH.

Stem Cell Research Unlocks Clues to Esophageal Cancer

The types of lesions include high-grade dysplasia, low-grade dysplasia and earlier lesions known as Barrett’s esophagus. These common evolutionary features place both cancers into a single cluster distinct from other gastric and esophageal cancers.

Stomach Cancer | Gastric Cancer
Stomach (gastric) cancer develops from the stomach lining. It is the third most common cause for cancer related deaths.

‘The study has revealed Barret’s esophagus and gastric intestinal metaplasia (GIM) stem cells are indistinguishable at the level of whole genome expression profiling down to the level of homeotic transcription factors that define cellular identity.’

While it was widely anticipated that advances in endoscopic and ablative technologies applied to precursor lesions would spell the end of EAC and iGC, the rate of those who suffer from them has not appreciably decreased, and most patients still present with advanced disease and poor five-year survival.

This dire clinical reality has inspired a broad effort to understand the cell-of-origin of these diseases, their earliest emergence towards pathology, as well as their detection and pharmaceutical elimination.

McKeon is the principal investigator on a new five-year, $4.7 million grant from the National Cancer Institute to advance this work. He’s joined on the research project by Wa Xian, research associate professor of biology and biochemistry at UH, and Dr. Jaffer Ajani MD of Anderson Cancer Center.

Esophageal Cancer - Types, Risk factors, Symptoms, Diagnosis, Treatment, Prevention, Prognosis
Esophageal cancer refers to malignancy of the food pipe which connects the throat to the stomach. It typically presents with difficulty in swallowing.

For over a decade, Xian has been perfecting technology for cloning stem cells and is fine tuning the technology to clone stem cells from the precursor lesions for these cancers.

“As all these lesions are still present in patients with advanced cancer, sequencing these patient-matched stem cells shows in exquisite detail the precise mutational changes that accompanied the evolution of the cancer,” said Xian.

The Splendid Stomach
Stomach is the organ where food is mixed, stored and partially digested.

Despite their emergence from disparate regions of the upper gastrointestinal tract, EAC and iGC show stunning similarities in their genetics and the precursor lesions in their evolution.

These markers have also enabled the cloning of the corresponding site-specific stem cells, which the team will do in both fetus and adult trials.

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“We anticipate that our studies will provide new insights into the biology and origin of these remarkably similar and widespread cancers, provide datasets essential for prospective early detection screens and yield highly selective therapeutics that eliminate the nascent lesions essential for the evolution of these cancers,” said McKeon.

Source-Eurekalert