Scientists have uncovered the mechanism behind how aspirin could reduce the metastasis of some cancers by stimulating the immune system, in a new study primarily funded by the Medical Research Council.
In the study, published in Nature, researchers discovered how aspirin might prevent the spread of susceptible cancers. This could support ongoing clinical trials and lead to more targeted use of aspirin or the development of new anti-metastasis drugs.
Previous studies have shown that daily low-dose aspirin can reduce the spread of cancers like breast, bowel, and prostate cancer, but the biological mechanism was unclear. This new study, led by the University of Cambridge, identified that aspirin works by lifting immune suppression.
The research team had been studying how the immune system responds to cancer metastasis, which accounts for 90% of cancer deaths. When individual cancer cells break away and spread to other parts of the body, they are more vulnerable to immune attack compared to cells within the primary tumor.
The researchers screened 810 genes in mice and found that removing one gene, ARHGEF1, significantly reduced cancer spread. ARHGEF1 was found to suppress T cells — immune cells responsible for killing cancer cells.
The team traced this suppression to a blood-clotting factor, thromboxane A2 (TXA2), which activates ARHGEF1. TXA2 is produced by blood platelets and plays a role in clotting. Aspirin is known to reduce TXA2 levels, explaining its anti-clotting effects.
Using mouse models of melanoma, the study confirmed that aspirin reduced the frequency of metastasis by lowering TXA2 levels and restoring T cell activity.
Professor Rahul Roychoudhuri, who led the study, emphasized the potential to prevent relapse in early-stage cancer patients by targeting the period when metastasizing cells are most vulnerable to immune attack.
Dr Jie Yang, co-author, described the discovery of TXA2’s role as a “Eureka moment” that shifted the direction of their research.
This discovery could help identify who is most likely to benefit from aspirin after a cancer diagnosis. The researchers are collaborating with Professor Ruth Langley, who leads the Add-Aspirin clinical trial, to study aspirin’s role in preventing cancer recurrence.
As aspirin may cause side effects in some individuals, the researchers caution that people should consult a doctor before beginning regular use.
This work was funded by the Medical Research Council, the Wellcome Trust, and the European Research Council. The Add-Aspirin trial is supported by Cancer Research UK, the NIHR, and the Tata Memorial Foundation of India.
The study is published in Nature.
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