A growing body of research shows that chronic inflammation can lead to serious health issues. In the stomach, long-term inflammation can damage the lining and trigger lesions to form – a condition known as gastric intestinal metaplasia (GIM), in which normal stomach cells begin to resemble intestinal cells. While not cancer at first, some of these lesions can progress to gastric cancer. And because early warning signs are subtle, many patients are diagnosed after the disease has advanced, when survival rates are significantly lower.
Today, patients diagnosed with GIM are placed into endoscopic surveillance programs where doctors regularly examine and biopsy the stomach lining, watching for signs that cells are becoming abnormal. When lesions become highly dysplastic, meaning they show clear signs of becoming cancerous, the affected tissue is removed to prevent cancer from developing.
This approach can be effective for some, but there is currently no reliable way to distinguish low-risk lesions from those likely to progress. As a result, patients with confirmed GIM undergo years of invasive monitoring, even though only a fraction will ever develop cancer.
Supported by $2 million from the Terry Fox Research Institute as part of a groundbreaking new cancer prevention initiative led by the Canadian Institutes of Health Research, a British Columbia-based team of researchers is working to change this.
Led by Dr. Isabella Tai, senior scientist at BC Cancer’s Michael Smith Genome Sciences Centre and a gastroenterologist at the University of British Columbia, the team will spend the next five years studying how pre-cancerous stomach lesions develop and why some progress into cancer while others do not.
To do this, they will collect samples of normal stomach tissue and stomach tissue with lesions from the same patients at different stages. Using advanced genetic tools, including spatial transcriptomics, they will explore how genes and proteins change over time.
They will then integrate this data to create a single-cell atlas, or a map of the genetic and protein profiles linked to high-risk lesions. This will help pinpoint specific genes, proteins and signalling networks involved in progression to cancer and uncover biomarkers that could identify patients at highest risk.
Finally, the team will validate these findings by creating gastric organoids – mini lab-grown models that mimic the structure and function of the stomach – using the tissue samples collected earlier in the project. Using additional genetic technologies, the team will turn the key genes identified on or off and observe how the organs change in shape and behaviour. By watching how these organoids respond, researchers can directly test the biological processes driving gastric lesions to progress into cancer.
Together, this work could provide the knowledge needed to transform how gastric lesions are monitored and treated, ultimately preventing cancer before it starts.
“This strategy would be a paradigm shift from passive surveillance to active treatment of gastric lesions, preventing gastric cancer from developing in the first place,” says Dr. Tai.
“For patients, this would mean that doctors could actively treat pre-malignant lesions to prevent cancer from developing rather than waiting to treat the cancer itself.”