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Stomach stem cells behaving badly | 2023 Metcalf Prize winner: Dustin Flanagan, Monash Biomedicine Discovery Institute

November 08, 2023

People diagnosed with late-stage stomach cancer have a less than 10 per cent chance of surviving more than 5 years.

Dr Dustin Flanagan wants to boost that survival rate by understanding why some deviant stomach stem cells turn cancerous. This knowledge will help in the development of drugs to bring these misbehaving cells back to normal, healthy function.

Dustin’s past research has led to the development of treatments for Crohn’s disease, bowel cancer, and other gastrointestinal conditions.

He’s now at Monash Biomedicine Discovery Institute turning his attention to stomach cancer, which is less common than bowel cancer but just as lethal.

In recognition of his leadership in the field, Dustin has received one of two 2023 $60,000 Metcalf Prizes from the National Stem Cell Foundation of Australia.

Stem cells in the harsh, acidic environment of the stomach have a tough job, continuously renewing the stomach lining and repairing injury. As stem cells replicate, they can acquire genetic mutations that make them super-competitive.

Dustin identified some of the mechanisms used by super-competitor cells in the colon to overthrow normal stem cells, initiate cancer, and form tumours. It’s informing his stomach cancer research.

“The really terrifying part is the poor survival rate for people with advanced stomach cancer,” he says.

A typical patient visits their doctor complaining of weight loss and feeling bloated but by this time, the cancer is likely to be advanced.

“The majority of patients come through the clinic door at a stage when treatment options are sadly limited. Nearly 1,200 Australians die from stomach cancer each year.”

So, how can we tackle these late-stage cancers?

Dustin recently returned to Melbourne to lead a group at Monash University focused on stomach stem cells and how they function in chronic infection and cancer initiation and progression.

This work draws on his doctoral research into intestinal stem cells, which led to the development of treatments for Crohn’s disease and Clostridium difficile infection, and his postdoctoral work on bowel cancer at the Cancer Research UK Beatson Institute in Glasgow, Scotland.

Dr Dustin Flanagan in the lab. Credit: Monash University

Dustin has changed our understanding of how stem cells behave after acquiring genetic mutations that favour cancer formation. He also wants to unravel how and why some stomach cancer stem cells survive treatment and become more aggressive and resistant to other therapies.

“Previously, I was looking at what controls whether stem cells in the colon behave as they should, or badly, and we found that we could target some of those abnormalities,” Dustin says.

“That turned out to be a powerful preventive against developing bowel tumours in mice. It’s quite exciting because that work is being taken forward by a company developing a therapy targeting the equivalent abnormalities in humans.”

Dustin will use his Metcalf Prize to take a similar approach to tackling stomach cancer. He and his team are investigating the ‘plasticity’ of cancer stem cells to find weaknesses that can be targeted with new drugs.

“Cancer stem cells have molecular ‘back-up plans’ that allow them to masquerade as other cell types to evade therapy and progress disease,” he says. “Little is known about the molecular blueprints that control stomach cancer stem cells in particular.”

Dustin’s goal is to make discoveries that have the potential to generate new therapies for therapy-resistant metastatic gastric cancer.

“But I hope my research will also produce powerful insights that can be shared with the broader cancer research community and applied to other cancers plagued by drug resistance, such as breast and lung cancer. Winning the Metcalf Prize provides the visibility to do just that.”

Stomach cancer facts

  • It is estimated that more than 2,500 Australians were diagnosed with stomach cancer in 2023.
  • The average age at diagnosis is 70 years old.[1]
  • In 2020, there were 1,182 deaths from stomach cancer in Australia (789 males and 393 females).
  • Globally, there were more than 768,000 deaths from stomach cancer in 2020.[2]
  • Stomach or ‘gastric’ cancer is the fifth leading cause of cancer deaths worldwide.
  • The rates and mortality of stomach cancer are particularly high in Asia due to high Helicobacter pylori infection, dietary habits, smoking behaviours, and heavy alcohol consumption.[3]
  • Actor and famously heavy drinker and smoker John Wayne died in 1979 from stomach cancer.





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