One of the oldest drugs in the world may still have new tricks up its sleeve. In research out today, scientists have found evidence in mice that aspirin can potentially prevent cancer from spiraling out of control.
Scientists at the University of Cambridge led the research, published Tuesday in the journal Nature. In mice, they found that aspirin seemed to unlock certain aspects of the immune system that make it better at stopping cancers trying to spread elsewhere in the body, also known as metastasis. The findings indicate that aspirin and similar drugs could be turned into preventative treatments for high-risk cancer patients, the researchers say.
Studies throughout the years have suggested that aspirin might have cancer-fighting potential—potential that made senior study researcher Rahul Roychoudhuri and his team curious enough to look into the question for themselves.
“Importantly, several large randomized controlled trials originally designed to study cardiovascular benefits of aspirin unexpectedly revealed that participants taking daily aspirin had reduced cancer deaths,” Roychoudhuri, a professor of cancer immunology at Cambridge, told Gizmodo. “What was particularly intriguing was that these beneficial effects appeared after only a few years of aspirin use—too quickly to be explained solely by prevention of new cancers.”
Based on this data, Roychoudhuri and others have speculated that aspirin is more effective at preventing cancer metastases rather than wholly new cases of cancer. Metastasized, or advanced, cancers are especially difficult to treat once they emerge, often leading to death. So the team set out to investigate the mechanisms behind this prevention by studying mice.
Across different models of cancer, including breast, colon, and skin cancer, the team found that aspirin-dosed mice had lower rates of metastasis compared to untreated mice. When they looked closer, the biologists uncovered a previously unknown pathway by which aspirin seems to improve the body’s immune response to cancer metastasis.
They found that aspirin inhibits the production of a particular substance released from platelets, the cell fragments in our blood that play a vital role in clotting but have other important functions as well. This substance, called thromboxane A₂ (TXA₂), suppresses the immune system’s ability to recognize and destroy cancer cells that have spread from the primary tumor, according to Roychoudhuri. Specifically, TXA₂ appears to suppress cancer-fighting T cells through a protein called ARHGEF1.
“When we gave aspirin to mice, it blocked the production of TXA₂ by platelets, thereby releasing T cells from this suppression and allowing them to attack metastatic cancer cells more effectively,” he said.
The findings provide a clear explanation for how aspirin works to prevent cancer from worsening, though Roychoudhuri notes that human studies will be needed to truly validate the results. He strongly cautions that people should not start taking aspirin for cancer prevention or treatment just because of their study, and not without consulting their doctor first. The clinical benefit of this cancer prevention may also be modest at best or may not apply to everyone equally. Contrary to other research involving younger people, for instance, a 2020 study found evidence that aspirin might actually increase the risk of cancer metastasis in people over 70.
But this research does lend support to the idea that aspirin can become a valuable part overall of the medical toolkit against cancer, given its low costs and general safety. And it could pave the way to other, possibly more effective therapies that work in a similar way.
“Our identification of the TXA₂-ARHGEF1 pathway provides a target for developing more selective therapies. Future drugs could potentially block this pathway more specifically than aspirin, which might offer the anti-metastatic benefits without the bleeding risks associated with long-term aspirin use,” Roychoudhuri notes.
Roychoudhuri and his team are already working to develop these next-generation drugs. They’re also collaborating with the researchers behind the ADD-ASPIRIN study, an ongoing clinical trial in the UK studying whether aspirin can improve cancer outcomes. And they’re investigating whether aspirin could be used in tandem with other treatments that boost the immune system’s response to cancer, such as checkpoint inhibitor therapy.
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