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Scientists have uncovered the mechanism by which aspirin stimulates the immune system and can reduce the metastasis of some cancers.
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. 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. In this study, led by researchers at the University of Cambridge, the scientists say their discovery of how aspirin reduces cancer metastasis was serendipitous. They were investigating the process of metastasis, because, while cancer starts out in one location, 90% of cancer deaths occur when cancer spreads to other parts of the body. The scientists wanted to better understand how the immune system responds to metastasis, because when individual cancer cells break away from their originating tumour and spread to another part of the body they are particularly vulnerable to immune attack. The immune system can recognise and kill these lone cancer cells more effectively than cancer cells within larger originating tumours, which have often developed an environment that suppresses the immune system. The researchers previously screened 810 genes in mice and found 15 that affected cancer metastasis. In particular, they found that mice lacking a gene that 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. 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. 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. (ANI)
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