At low doses, taking aspirin reduces the risk of cancer spreading—called metastases—and the risk of dying from it. While this has been known since around the 2010s, no one knew how to explain it… until now. And as often happens in science, this discovery owes much to chance.
A study on metastases that accidentally leads to aspirin
“ Initially, we were not specifically studying aspirin.", notes Rahul Roychoudhuri, an immunologist specializing in oncology at the University of Cambridge (England) who led this work published in the journal NatureIn the search for genetic factors that regulate metastases in cancer, researchers identified a gene in mice. Named ARHGEF1, its disruption in certain immune cells reduced the frequency of metastases. These immune cells are T cells, white blood cells (or lymphocytes, as they are scientifically known) that specialize in eliminating abnormal cells, such as cancer cells.
Be careful not to take aspirin without consulting your doctor., warns Rahul Roychoudhuri, recalling that this work has so far only been carried out on mice. If the TXA₂/ARHGEF1 pathway exists in humans, its relative importance in human cancer metastasis may differ from that in mice. Human cancers are generally more heterogeneous and develop over longer periods than mouse models.. » In addition, aspirin causes many potentially serious side effects such as bleeding, which can lead to hemorrhage or certain types of stroke. Finally, " The optimal timing, dosage, and duration of aspirin treatment to prevent metastases in humans remain uncertain.", points out the researcher, clinical trials on the subject being underway.
“ The link with aspirin emerged when we investigated which extracellular signals could activate ARHGEF1 in T cells", says Rahul Roychoudhuri. They then identified the culprit, a molecule released by blood platelets (which enable coagulation) and called thromboxane A2 (TXA2). " This was our stroke of genius, because aspirin is known to inhibit the production of TXA₂!“
Read alsoThe anticancer virtues of aspirin confirmed
Let's recap, because the situation is complex. Under normal conditions, platelets produce TXA2, which reaches immune T cells. In just a few minutes, this signal activates their ARHGEF1 gene, which effectively deactivates them against tumor cells. Platelets release a substance called thromboxane A₂ (TXA₂) which essentially tells these T cells to 'stand down'", summarizes Rahul Roychoudhuri. In the presence of aspirin, this entire system is rendered useless, because the drug blocks the production of TXA2. " This amounts to removing the 'standby' order, allowing T cells to be more active and effective at finding and killing cancer cells that have broken away from the original tumor“.
The researchers observed the lung tissue of mice with a breast tumor. On the left, the mice developed metastases (black dots), while on the right, mice lacking the ARHGEF1 gene did not. Credit: Jie Yang
Targeting metastatic cells when they are most vulnerable
It is at this moment when cancer cells detach from the original tumor that they are most vulnerable, the researchers say. They have not yet established the protective immunosuppressive environment found in larger tumors", Rahul Roychoudhuri explains. Moreover, ARHGEF1 has a profound impact on metastases, but minimal on the growth of established primary tumors, he adds.
This is probably why taking aspirin would have the best results before the onset of metastases. At a low dose (75 to 300 mg per day, compared to a usual dosage of 500 mg to 2 g), it allows a reduction of 36% in the risk of metastases in cancers and halves mortality from cancer without metastases at the time of diagnosis according to the Lancet in 2012.
A variable effect depending on the cancers
These new results would also explain why aspirin is not equally effective against all types of cancer. Aspirin is particularly effective against adenocarcinomas such as colorectal, gastric, and some breast and lung cancers, but less so against other types of cancer.“, specifies Rahul Roychoudhuri. “ However, many adenocarcinomas are known to elicit T-cell responses, and their metastatic process often involves interactions with platelets in the bloodstream.. » If this work is verified in humans, it could allow the development of more specific treatments than aspirin acting directly on TXA2 or the ARHGEF1 gene.
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