Scientists from A*STAR Institute of Molecular and Cell Biology (A*STAR IMCB) revealed on Friday (Dec. 19) they have identified the stem cells responsible for gastric cancer. They also reveal that removing these stem cells stops tumours from growing, even in advanced stage patients where the cancer has spread to other organs.
The study, published in “Science”, says the scientists discovered the marker of cancer stem cells, a protein called Aquaporin-5 (AQP5), and eliminating the AQP5-expressing cells in a laboratory setting shows that the tumours shrank and did not come back.
The discovery is a breakthrough for patients with gastric cancer which remains a significant health burden for Singaporeans and others across Asia, where incidence rates are among the highest in the world.
More than two-thirds of patients are diagnosed at advanced stages of the cancer, often leading to low survival rates.
One of the greatest challenges is the frequency of the occurrence of gastric cancer. A patient who has recovered from treatment may suffer relapse within months or years, often spreading to other parts of the body such as the liver or lungs.
Scientists have long suspected that a small population of cancer stem cells survives the cancer treatment and regenerates the tumour. They are thought to resist conventional therapies, allowing the disease to return even after the visible tumour has been removed.
Scientists have also used other protein markers, known as CD44 or CD133 to identify gastric cancer stem cells but results were inconsistent. These markers often appear on healthy cells.
The A*STAR team discovered that AQP5 reliably marks the cancer stem cells in gastric tumours. Aquaporins are proteins that form channels in cell membranes to control the movement of water into and out of cells. The study shows it identifies the AQP5 cells which are responsible for driving tumour growth, spread, and recurrence.
The study also reveals that AQP5 actively contributes to the aggressive development of tumour growth. The studies employed a targeted method to eliminate only the AQP5-expressing cells and found that tumours stopped growing or shrank entirely and did not recur. This held true even for cancers that had spread to other organs.
Prof Nick Barker, Senior Principal Scientist at A*STAR IMCB said “These findings give us a defined target to pursue. We are now working to develop therapies against AQP5-expressing cells that could offer patients a better chance of lasting remission.”
Targeted Therapies for Gastric Cancer
The discovery builds on Prof Barker’s 2020 research, published in “Nature,” which identified AQP5 as a marker of stem cells in healthy gastric tissue. The current study shows that these healthy stem cells when turned cancerous retain AQP5, making it a reliable way to identify the cells that drive tumour growth.
The findings point to AQP5 as a potential target for new gastric cancer treatments. The research team is now developing AQP5-specific antibodies and evaluating drug candidates, with the aim of conducting preclinical studies. This process typically takes many years as any therapy would need to be tested in clinical trials before it could be used in patients.
The study was led by Prof Nick Barker, Senior Principal Scientist at A*STAR IMCB, with Dr Grace Lim and Swathi Yada as co-first authors.
Dr Lim was awarded the 2024 L’Oréal-UNESCO For Women in Science fellowship for her work on gastric cancer stem cells while Prof Barker is an internationally recognised authority in gastrointestinal stem cell biology whose 2007 discovery of LGR5 as a marker of intestinal stem cells, published in “Nature”, established foundational tools now used in cancer research worldwide. He has been recognised among the world’s top 2% most-cited scientists for six consecutive years (2020–2025) in the Stanford University–Elsevier global ranking.
