Aspirin, a new ally against cancer: metastasis is stopped in a novel experiment with mice

This common drug can prevent T cells from being inhibited, improving their ability to destroy cancer cells.. Angel Lanas, scientific director of the IIS Aragón, explains it to Science Media Center

El acetylsalicylic acid, commonly known as aspirin, has demonstrated the ability to inhibit cancer metastasis in a laboratory experiment. The researchers worked with models of Mice with breast cancer, colon cancer and melanoma, in which the administration of aspirin prevented the spread of cancer cells to organs such as the lungs and liver.

As the authors explain in the journal Nature, Their discovery paves the way for the use of more effective anti-metastatic immunotherapies through selective aspirin administration to prevent the spread of certain types of cancer. However, they remember that this medication causes Adverse effects some patients experience bleeding or stomach ulcers, which is why future clinical trials are being held.

"We know that people who take aspirin daily have a lower risk of cancer. Even after diagnosis, it is associated with a lower risk of metastasis," he explains. Science Media Center the professor Angel Lanas, head of the Digestive Service at the Lozano Blesa University Clinical Hospital in Zaragoza and scientific director of the Aragon Health Research Institute (IIS Aragón). The hypothesis was that this effect depended on platelets and was related to immunity.

Jie Yang, from the team of researchers from the University of Cambridge that led the international study, defines it as a "moment eureka«. They were investigating the process of metastasis, since 90% of mortality attributable to cancer occurs when it begins to extend from one organ to the rest. These cancer cells are, however, more vulnerable to the immune system as they migrate, since those that remain close to the tumor take advantage of the immunosuppressive environment it generates.

Scientists had previously inventoried 810 mouse genes, of which 15 were linked to a direct effect on metastasis. Rodents lacking a gene encoding the protein ARHGEF1 showed a lower extension of cancer to the lungs and liver. The absence of this element prevented the suppression of T lymphocytes, immune system cells that can recognize and destroy cancer cells. 

They then analyzed cellular signals to determine that ARHGEF1 activation occurs when lymphocytes are exposed to a thrombotic factor called thromboxane A2 (TXA2). This compound, produced by platelets that help blood clot to prevent wounds from causing bleeding, is related to aspirin. This drug reduces the production of TXA2, so it benefits cardiovascular patients who are prone to blood clots.

In mice with melanoma given aspirin, suppression of TXA2 increased the availability of T cells, which reduced the frequency of metastasis. “This was a completely unexpected finding. And it opens up a whole new line of research,” Yang said. “Both aspirin and other prostaglandin synthesis inhibitor drugs will be cheaper therapies than those based on prostaglandin.” monoclonal antibodies, and therefore, more accessible." 

"Deductive research is brilliant," says the professor Ignacio Melero, CIMA researcher and co-director of the Department of Immunology and Immunotherapy at the University of Navarra Clinic. "They had discovered a factor that is involved in facilitating metastasis in mice. In the screening, a protein appeared whose levels increase with thromboxane A2. From there, they found that thromboxane favors metastasis by an immunosuppressive mechanism and through this route they observed that aspirin decreases the efficiency of metastasis."

«The data suggest that we should explore If the consumption of low-dose aspirin is antiplatelet "It reduces the probability of metastasis in cancer patients, or if patients who receive aspirin are less frequently diagnosed in the metastatic stage," Melero continues. "Previous work, to which this one is now added, gives reasons for carrying out clinical trials "in which prostaglandin synthesis is blocked in the context of immunotherapy treatments that we routinely apply to patients."

Source: The Spanish

Main Image: Mouse lungs with tumors due to metastasis (black dots) in the untreated mouse compared to the mouse that received aspirin.