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In a nutshell
- Aspirin may help prevent cancer from spreading by stopping platelets from producing thromboxane A2 (TXA2), which normally suppresses immune T cells from attacking metastasizing cancer cells.
- This newly discovered mechanism explains observations from clinical studies that daily low-dose aspirin can reduce cancer metastasis and deaths in some patients.
- While promising, aspirin can cause serious side effects in some people, so patients should consult their doctor before starting any aspirin regimen for cancer prevention.
CAMBRIDGE, England — Every medicine cabinet staple has a story, but few have a plot twist quite like aspirin. Most of us reach for this familiar white pill to quell a headache or reduce fever, yet beneath its humble appearance lies a potential cancer-fighting superhero. A study reveals that aspirin’s talents extend far beyond pain relief—it may help prevent cancer from spreading throughout the body by boosting our immune system’s ability to fight off metastasis.
Researchers from the University of Cambridge and several international institutions have discovered a previously unknown pathway explaining how aspirin protects against cancer metastasis, the lethal process responsible for 90% of cancer deaths worldwide. Their work, published in Nature, shows that aspirin works by preventing platelets—tiny blood cells known for clotting—from suppressing our immune system’s T cells, the body’s natural cancer fighters.
“Despite advances in cancer treatment, many patients with early stage cancers receive treatments, such as surgical removal of the tumor, which have the potential to be curative, but later relapse due to the eventual growth of micrometastases – cancer cells that have seeded other parts of the body but remain in a latent state,” explains lead author Professor Rahul Roychoudhuri from the University of Cambridge, in a statement.
The Vulnerable Window for Metastasizing Cancer
Cancer becomes most dangerous when it spreads from its original location to distant organs—a process called metastasis. When cancer cells break away from a primary tumor and travel through the bloodstream, they lack the protective environment found in established tumors, making them vulnerable targets for our immune system’s T cells.
“Most immunotherapies are developed to treat patients with established metastatic cancer, but when cancer first spreads there’s a unique therapeutic window of opportunity when cancer cells are particularly vulnerable to immune attack,” notes Professor Roychoudhuri. “We hope that therapies that target this window of vulnerability will have tremendous scope in preventing recurrence in patients with early cancer at risk of recurrence.”
The research team discovered that platelets release a substance called thromboxane A2 (TXA2), which attaches to receptors on T cells and activates a protein called ARHGEF1. This interaction suppresses T cell function, essentially crippling our natural anti-cancer defenses when they should be attacking vulnerable metastasizing cells.
Dr. Jie Yang described the moment of discovery: “It was a Eureka moment when we found TXA2 was the molecular signal that activates this suppressive effect on T cells. Before this, we had not been aware of the implication of our findings in understanding the anti-metastatic activity of aspirin. It was an entirely unexpected finding which sent us down quite a different path of inquiry than we had anticipated.”
How Aspirin Blocks Cancer’s Escape Route
Aspirin blocks the production of TXA2 by inhibiting an enzyme called cyclooxygenase-1 (COX-1) in platelets. By stopping platelets from producing TXA2, aspirin frees T cells from their suppressed state, letting them recognize and eliminate metastasizing cancer cells before they can establish new tumors.
When mice with cancer were treated with aspirin, they developed far fewer metastatic tumors than untreated mice. This protective effect disappeared in mice genetically engineered to lack ARHGEF1 specifically in their T cells, confirming that aspirin’s anti-metastatic effects work by freeing T cells from TXA2-mediated suppression.
The practical relevance of this research is particularly exciting. Unlike many experimental cancer therapies that require years of development before reaching patients, aspirin is already widely available, inexpensive, and has a well-established safety profile.
“Aspirin, or other drugs that could target this pathway, have the potential to be less expensive than antibody-based therapies, and therefore more accessible globally,” said Dr. Yang.
Make Sure To Check With Your Doctor
The findings from this study will support ongoing clinical trials, including the Add-Aspirin trial led by Professor Ruth Langley. “This is an important discovery. It will enable us to interpret the results of ongoing clinical trials and work out who is most likely to benefit from aspirin after a cancer diagnosis,” commented Professor Langley.
The researchers emphasize that aspirin isn’t without risks. “In a small proportion of people, aspirin can cause serious side effects, including bleeding or stomach ulcers. Therefore, it is important to understand which people with cancer are likely to benefit and always talk to your doctor before starting aspirin,” the researchers advise.
Who would have thought that the humble pill we take for headaches might one day join the front lines in our battle against cancer? As we continue to unravel the mysteries of how our bodies fight disease, it seems fitting that aspirin, one of medicine’s oldest allies, still has a few tricks up its sleeve.
Paper Summary
Methodology
The research team conducted their investigations using a combination of laboratory and animal studies. They began by examining how ARHGEF1 deficiency affected cancer metastasis in mice. Mice lacking ARHGEF1 developed significantly fewer lung metastases after injection of melanoma cells compared to normal mice.
To determine which immune cells were involved, the researchers created mice with ARHGEF1 deleted only in specific cell types. While deletion in other immune cells had no effect on metastasis, deletion specifically in T cells dramatically reduced metastases, indicating that ARHGEF1 primarily suppresses anti-cancer immunity through its effects on T cells.
Laboratory tests identified thromboxane A2 (TXA2), produced primarily by platelets, as the key molecule that activates ARHGEF1 in T cells to suppress their function. When mice were treated with aspirin, which blocks TXA2 production, they developed fewer metastases—but this protective effect disappeared in mice whose T cells lacked ARHGEF1, confirming that aspirin works through this pathway.
Study Limitations
While the results in mice were compelling, human physiology can differ in important ways, so these findings will need confirmation in human studies. The study focused primarily on melanoma and lung cancer models, so the mechanism might vary in other cancer types. The research also didn’t establish optimal dosing strategies that would maximize anti-cancer benefits while minimizing bleeding risks, which remains an important consideration for clinical application.
Funding and Publication Information
The research was principally funded by the Medical Research Council, with additional funding from the Wellcome Trust and European Research Council. The Add-Aspirin clinical trial is funded by Cancer Research UK, the National Institute for Health and Care Research, the Medical Research Council and the Tata Memorial Foundation of India.
This study, titled “Aspirin prevents metastasis by limiting platelet TXA2 suppression of T cell immunity,” was published in the prestigious journal Nature on March 5, 2025. The research was led by Jie Yang and Rahul Roychoudhuri from the Department of Pathology at the University of Cambridge.
