Researchers Find Possible Link Between Aspirin and Reduced Cancer Metastasis
How a common painkiller could aid the reduction of cancer metastasis.
A new study led by researchers at the University of Cambridge has revealed the mechanism behind how aspirin could reduce metastasis of some cancers by stimulating the immune system. The discovery may lead to the targeted use of aspirin to suppress the spread of susceptible cancers and aid the development of more effective drugs for preventing metastasis. The study was published in Nature.
Metastatic cancer cells are vulnerable to immune system attack
Metastasis – the spread of cancer cells from primary tumors to distant organs – is the cause of 90% of cancer deaths globally. Metastasizing cancer cells are often deprived of the immunosuppressive microenvironment found within established tumors, making them vulnerable to immune attack. This creates an opportunity for anti-metastatic therapies utilizing the immune system to prevent cancer recurrence.
Although previous studies have observed daily low-dose aspirin can reduce metastasis in some cancers (e.g., breast, prostate and bowel cancers), the mechanism by which this occurred was unknown – until now.
The researchers wanted to better understand how the immune system responds to metastasis. Interestingly, the immune system can recognize and kill these lone cancer cells more effectively than cancer cells within larger originating tumors.
“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”, said Dr. Rahul Roychoudhuri, a professor of cancer immunology at the University of Cambridge.
“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. 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,” he continued.
TXA2 suppresses T cell function
In a previous study, the researchers screened 810 genes in mice, finding that 23 affected cancer metastases. Specifically, mice lacking a gene that produces a protein called ARHGEF1 had reduced metastasis of various primary lung and liver cancers.
The protein ARHGEF1 suppresses T cells – a type of immune cell that can recognize and kill cancer cells. In the current study, Roychoudhuri and team discovered that when T cells are exposed to the clotting factor thromboxane A2 (TXA2), ARHGEF1 is switched on.
Serendipitously, TXA2 is very well known and linked to how aspirin works.
Produced by platelets, TXA2 helps the blood clot and prevents excessive bleeding, but it can also occasionally cause heart attacks and strokes. Aspirin reduces TXA2 production, leading to anti-clotting effects, hence reducing the risk of heart attacks and strokes.
This new research found that aspirin could prevent some cancers from spreading by reducing TXA2 and activating previously suppressed T cells. In a melanoma mouse model, the results showed that in mice given aspirin, the frequency of metastases was reduced compared to the control mice – which was dependent on increased T-cell activation from reduced TXA2.
“It was a Eureka moment when we found TXA2 was the molecular signal that activates this suppressive effect on T cells,” said Dr. Jie Yang, a postdoctoral scientist at the University of Cambridge. “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.”
“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,” he added.
Translating the findings into clinical practice
Roychoudhuri and the team now plan to help with the translation of their findings into potential clinical practice through collaboration with other scientists – such as Professor Ruth Langley.
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Langley, a professor of oncology and clinical trials at University College London MRC Clinical Trials Unit, is leading the Add-Aspirin clinical trial, to find out if aspirin can stop or delay early-stage cancers from coming back.
“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,” she said.
However, Roychoudhuri and the team urge interpreting their results with caution. In some people, aspirin can have serious side effects. Clinical trials are underway to determine how to use it safely and effectively to prevent cancer spread, so people should consult their doctor before starting to take it.
“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,” Langley concluded.
Reference: Yang J, Yamashita-Kanemaru Y, Morris BI, et al. Aspirin prevents metastasis by limiting platelet TXA2 suppression of T cell immunity. Nature. 2025:1-10. doi: 10.1038/s41586-025-08626-7
This article is a rework of a press release issued by UK Research and Innovation. Material has been edited for length and content.
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