Scientists on ‘Eureka moment' over how aspirin prevents cancer spread
Scientists have described the 'Eureka moment' when they discovered how aspirin may prevent some cancers from spreading.
Their new research builds on existing evidence and suggests aspirin supports a boost in the immune system to help catch deadly cancer cells.
Clinical trials in cancer patients are currently continuing into how aspirin could help stop the disease coming back.
However, experts said cancer patients should not routinely take aspirin without speaking to their doctor because of potential side-effects, such as bleeding in the stomach.
The new work was published in the journal Nature and funded by the Medical Research Council and Wellcome Trust.
Led by the University of Cambridge, it suggests a path for aspirin to become a cancer treatment, alongside the development of more effective drugs to prevent cancer spreading.
Researchers screened 810 genes in mice and found 15 that had an effect on cancer spread.
In particular, they found that mice lacking a gene which produces a protein called ARHGEF1 were less likely to have cancer spread to the lungs and liver.
The experts discovered that ARHGEF1 suppresses a type of immune cell called a T cell, which is important for recognising and killing metastatic (spreading to other parts of the body) cancer cells.
They found that ARHGEF1 is switched on when T cells are exposed to a clotting factor called thromboxane A2 (TXA2) – this was an unexpected finding for the scientists.
TXA2 is produced by platelets in the blood and aspirin is already known to cut the production of TXA2.
The research found that aspirin can prevent cancers from spreading by decreasing TXA2 – releasing T cells from being suppressed so they can kill cancer cells.
In mice given aspirin, the frequency of metastases was reduced compared with mice not on the drug, and this was dependent on releasing T cells from suppression by TXA2.
Professor Rahul Roychoudhuri, from the University of Cambridge, who led the study, said: 'Despite advances in cancer treatment, many patients with early stage cancers receive treatments, such as surgical removal of the tumour, 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.
'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.'
Dr Jie Yang, also from the University of Cambridge, said: '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.
'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.'
Researchers are now working with Professor Ruth Langley 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.
This trial, supported by Cancer Research UK, includes patients with breast, oesophageal, stomach, prostate and bowel cancer.
Professor Langley said of the new work: '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.'
Alan Melcher, professor of translation immunotherapy at the Institute of Cancer Research, London, said the side-effects of aspirin are not trivial – such as stomach bleeding.
He added: 'This new research may help to design better, more targeted drugs, that interfere with the mechanism discovered here to do the good things that aspirin does, without the harmful side-effects.'
Tanya Hollands, research information manager at Cancer Research UK, said further work is needed.
She added: 'At the moment, there are no national guidelines for the general population to take aspirin to prevent or treat cancer…
'Cancer Research UK is funding similar research, including the Add-Aspirin trial, the world's largest clinical trial designed to look at aspirin as a way to stop cancer coming back after receiving cancer treatment. We look forward to seeing how research develops in this area.'
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