Aquaporins in cancer stem cells targeted to prevent gastric cancer recurrence
Scientists have identified the specific cells responsible for gastric cancer's tendency to return after treatment. The study also demonstrated that eliminating these cells stops tumors from growing, even in advanced disease that has spread to other organs.
The study, published in Science, reveals that a protein called Aquaporin-5 (AQP5) marks these cells. When the researchers selectively eliminated AQP5-expressing cells in laboratory models, tumors shrank and did not return.
Gastric cancer remains a significant health burden in Singapore and across Asia, where incidence rates are among the highest in the world. More than two-thirds of patients are diagnosed at advanced stages, contributing to poor survival outcomes.
One of the greatest challenges is that the disease frequently recurs. A patient may undergo surgery or chemotherapy and show no signs of remaining disease, only for the cancer to reappear months or years later, often having spread to organs such as the liver or lungs.
Scientists have long suspected that a small population of cells survives treatment and regenerates the tumor. These "cancer stem cells" are thought to resist conventional therapies, allowing the disease to return even after the visible tumor has been removed.
Previous attempts to identify gastric cancer stem cells using other protein markers, such as CD44 or CD133, yielded inconsistent results. These markers often appeared on healthy cells as well or did not fully account for tumor behaviour.
The team discovered that AQP5 reliably marks the cancer stem cells in gastric tumors. Aquaporins are proteins that form channels in cell membranes to control the movement of water into and out of cells. While AQP5 was previously known to mark stem cells in healthy gastric tissue, this study shows it also identifies the specific cells responsible for driving tumor growth, spread, and recurrence.
Importantly, AQP5 does more than simply mark these cells; it actively contributes to their aggressive behavior.
The researchers found that cells with AQP5 were capable of forming new tumors, while cells without AQP5 rarely did so. Most significantly, when they used a targeted method to eliminate only the AQP5-expressing cells, tumors stopped growing or shrank entirely and did not recur. This held true even for cancers that had spread to other organs.
"Gastric cancer's high recurrence rate has long posed a challenge for clinicians," said a Senior Principal Scientist. "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."
The discovery builds on earlier research published in Nature, which identified AQP5 as a marker of stem cells in healthy gastric tissue. These normal stem cells are responsible for the continuous renewal of the stomach lining. The current study shows that when these stem cells become cancerous, they retain AQP5, making it a reliable way to identify the cells that drive tumor 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. Any therapy would need to be tested in clinical trials before it could be used in patients. This process typically takes many years.
