A team of researchers from the University of Cambridge (United Kingdom) has discovered, in mice experiments, the mechanism by which aspirin could avoid metastasis in some types of cancer.
The authors of the research, collected this Wednesday in the magazine Naturethey warn that their finding will support the current clinical trials to analyze the effectiveness of aspirin to prevent the spread of cancer in humans. “The finding is paving the way to the use of more effective antimastastic immunotherapies, ”says scientists, while warning of any person with cancer, this drug should be taken without medical prescription, EFE reports, since it can have serious side effects such as altering the stomach lining and increasing the risk of intestinal hemorrhages.
“The study seems excellent to me,” Pondera Ángel Lanas, a professor at the Faculty of Medicine of the University of Zaragoza and head of the Digestive Service of the Lozano Blesa University Hospital in Zaragoza in statements to the Media Center (SMC) University of Spain. “Explore a pathogenic pathway related to metastasis and the effect of acetylsalicylic acid (aspirin, AAS) that, under my knowledge, had not been explored with so much depth and in such a complete way at an experimental level.”
“We know (…), for many years, that people who take daily AAS have less risk of cancer and lower mortality associated with cancer,” continues the doctor. (…) We knew that AAS taking, even after having made the diagnosis of cancer, it was associated with a lower risk of metastasis. The suspicion that this effect was dependent on platelets and possibly related to immunity has always been present, but the mechanism was not clear beyond plausible hypotheses. This work is an important step to respond to this hypothesis confirming it and opens new therapeutic paths associated with immunotherapy, which is so good results in many tumors. ”
This expert coincides with his colleague Ramón Salazar, head of the Medical Oncology Service of the Catalan Institute of Oncology in L’Hospitalet (ICO), in which in the future “the greatest limitation is the usual in preclinical research, and that is that what happens in preclinical models does not necessarily occur in the human organism. In fact, in several randomized trials in adjustance in colon and breast cancer, aspirin has not improved the results of relapse free survival or global survival, ”he explained to the SMC.
“The complexity in the human is greater and less controllable than in experimental conditions,” says Llanas. “It is very possible that this interesting effect is seen only in some types of cancer that express a specific molecular profile that will have to be better defined.”
A casual finding
In the case of experiments with mice carried out for this study, the finding that aspirin can avoid cancer expansion was “fruit of chance” when the authors tried to better understand how the immune system responds to metastases.
The researchers analyzed 810 genes in mice and discovered that 15 of them influenced cancer metastasis. Specifically, they saw that the mice that lacked a gene that produces the arhgef1 protein suffered less metastases from primary cancers to the lungs and liver. The explanation, says the study, is that the ARHGEF1 protein suppresses the immune cells T, which effectively recognize and eliminate metastatic cancer cells.
Next, scientists saw that the ARHGEF1 protein is activated when T cells are exposed to a coagulation factor called thromboxan A2 (Txa2), well known, since it is related to how aspirin works. The TXA2 is produced by platelets, blood torrent cells that help blood clotting, preventing wounds from bleeding, but being able to promptly cause myocardial infarctions and strokes. When recipienting the production of TXA2, aspirin causes the anticoagulant effects that prevent these diseases.
The effect on mice
In this study, the authors have used a melanoma model in mouse to demonstrate that metastasis was reduced in the rodent group to which aspirin was administered in front of those who did not receive it.
“Aspirin prevented cancers from spreading in the mice by decreasing TXA2 and releasing the T cells from their suppression,” says Rahul Roychoudhuri, a researcher at the University of Cambridge and one of the study authors. “It was exciting to discover that TXA2 was the molecular signal that activated this suppressor effect on T cells against metastasis. Aspirin or other drugs that use this mechanism are less expensive than antibody -based therapies and, therefore, more accessible worldwide, ”adds its colleague and co -author Jie Yang, from the same university.
Caution
But does this study imply that cancer patients should take a low dose of aspirin daily to prevent cancer propagation? The response according to the biologist and oncologist at Reading University, Harvey Roweth, is clearly “No”, according to a reaction collected by Science Media Center.
“This study with mice implies that we must continue to evaluate the role of aspirin in human metastatic cancer. Previous clinical studies on this subject have been contradictory already often conclusive. There are even some reports that conclude that aspirin can do more bad than good, ”says Roweth.
“We are facing an interesting finding. The discovered mechanism can help design better and more specific drugs against metastasis, without the harmful side effects of aspirin, ”says Alan Melcher, professor of immunotherapy at the London Oncological Research Institute.
In addition to the limitation of having done with mice, this study has focused only on a few types of cancer (breast, intestine and prostate) and only in the lung and liver as metastatic locations.
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