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In the study, published in Nature, the scientists say that discovering the mechanism will support ongoing clinical trials, and could lead to the targeted use of aspirin to prevent the spread of susceptible types of cancer, and to the development of more effective drugs to prevent cancer metastasis.
The scientists caution that, in some people, aspirin can have serious side-effects and 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.
Studies of people with cancer have previously observed that those taking daily low-dose aspirin have a reduction in the spread of some cancers, such as breast, bowel, and prostate cancers, leading to ongoing clinical trials. However, until now it wasn’t known exactly how aspirin could prevent metastases.
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The researchers previously screened 810 genes in mice and found 15 that had an effect on cancer metastasis. In particular, they found that mice lacking a gene which produces a protein called ARHGEF1 had less metastasis of various primary cancers to the lungs and liver.
The researchers determined that ARHGEF1 suppresses a type of immune cell called a T cell, which can recognise and kill metastatic cancer cells.
To develop treatments to take advantage of this discovery, they needed to find a way for drugs to target it. The scientists traced signals in the cell to determine that ARHGEF1 is switched on when T cells are exposed to a clotting factor called thromboxane A2 (TXA2).
This was an unexpected revelation for the scientists, because TXA2 is already well-known and linked to how aspirin works.
TXA2 is produced by platelets — a cell in the blood stream that helps blood clot, preventing wounds from bleeding, but occasionally causing heart attacks and strokes. Aspirin reduces the production of TXA2, leading to the anti-clotting effects, which underlies its ability to prevent heart attacks and strokes.
This new research found that aspirin prevents cancers from spreading by decreasing TXA2 and releasing T cells from suppression. They used a mouse model of melanoma to show that in mice given aspirin, the frequency of metastases was reduced compared to control mice, and this was dependent on releasing T cells from suppression by TXA2.
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In the future, the researchers plan to help the translation of their work into potential clinical practice by collaborating with Professor Ruth Langley, of the MRC Clinical Trials Unit at University College London, who is leading the Add-Aspirin clinical trial, to find out if aspirin can stop or delay early stage cancers from coming back. Professor Langley, who was not involved in this study, commented: “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.
“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.”
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Source: Scientists discover how aspirin could prevent some cancers from spreading | ScienceDaily
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