Aspirin’s Potential Role in Cancer Metastasis Prevention: A New Study Explores the Link

A recent study from the University of Cambridge has ignited a renewed interest in the potential role of aspirin, a common over-the-counter pain reliever, in preventing the spread of certain cancers. The research, published in the prestigious journal Nature on March 5th, suggests that aspirin may reduce cancer metastasis – the process by which cancer cells spread from the original tumor to other parts of the body – by stimulating the body’s own immune system.

The findings, primarily based on studies conducted in mouse models, revealed a fascinating mechanism by which aspirin may exert its anti-metastatic effects. Scientists discovered that a protein called ARHGEF1 plays a crucial role in suppressing the activity of T-cells, which are specialized immune cells responsible for identifying and attacking cancer cells that have broken away from the primary tumor. These rogue cancer cells are the seeds of metastasis, and their elimination is critical in preventing the disease from spreading.

The study unveiled that ARHGEF1 is activated when T-cells are exposed to thromboxane A2 (TXA2), a chemical produced by platelets, tiny blood cells that play a vital role in blood clotting. While TXA2 is essential for normal blood clotting and wound healing, excessive production can increase the risk of serious cardiovascular events such as heart attacks and strokes.

This is where aspirin enters the picture. Aspirin is already known to inhibit the production of TXA2, thereby preventing excessive blood clotting. This is why it is often recommended for individuals at high risk of heart attacks or strokes. The new research suggests that aspirin’s ability to decrease TXA2 levels also plays a crucial role in releasing T-cells from the suppressive effects of ARHGEF1. By effectively freeing up these immune cells, aspirin may empower the body’s natural defenses to target and destroy circulating cancer cells, ultimately reducing the risk of metastasis.

In experiments involving mice with melanoma, a type of skin cancer, researchers observed that those treated with aspirin experienced significantly less frequent metastases compared to those who did not receive the medication. This finding provides compelling evidence for the potential of aspirin to inhibit cancer spread.

Dr. Jie Yang, the first author of the study from the Department of Pathology at the University of Cambridge, described the moment of discovery as a "eureka" moment, emphasizing the unexpected nature of the finding. He stated that the realization that TXA2 was the molecular signal responsible for suppressing T-cell activity was a breakthrough in understanding the anti-metastatic properties of aspirin.

The researchers also highlighted the potential for aspirin, or other drugs targeting the same pathway, to offer a more affordable and accessible alternative to antibody-based therapies, which are often expensive and may not be readily available in all parts of the world.

Senior researcher Dr. Rahul Roychoudhuri, a professor of cancer immunology at the University of Cambridge, noted that previous studies have suggested a link between daily aspirin use and a reduced risk of cancer spread in humans, as well as decreased cancer mortality in patients without existing metastasis. He also cited a randomized controlled trial where daily intake of 600 milligrams of aspirin for an average of 25 months significantly reduced cancer incidence in individuals with a hereditary predisposition to colorectal cancer.

Dr. Pashtoon Kasi, a medical director of gastrointestinal medical oncology at City of Hope Orange County in California, who was not involved in the study, echoed the sentiment that previous research has indeed associated aspirin use with a reduced risk of cancer, particularly cancers of the gastrointestinal tract. He acknowledged that studies have shown mixed results regarding aspirin’s effectiveness in reducing cancer recurrence or improving outcomes in patients with metastatic cancer. However, he believes that this new study adds valuable information to the growing body of evidence, providing mechanistic insights into how aspirin might exert its effects from an immunological perspective.

Despite the promising findings, researchers are urging caution and emphasizing that patients should not start taking aspirin for cancer prevention without consulting their doctor. While aspirin is readily available and inexpensive, long-term use is associated with significant risks, including stomach bleeding and hemorrhagic stroke, especially in older individuals.

Dr. Roychoudhuri stressed that the risk-benefit calculation varies considerably between individuals, depending on factors such as age, pre-existing medical conditions, and concurrent medications. Therefore, patients interested in exploring aspirin therapy should engage in a thorough discussion with their oncologist or family practitioner to carefully evaluate the potential benefits against the risks.

Dr. Kasi also pointed out the limitations of the current study, primarily the fact that the research was conducted on mice models rather than humans. He also highlighted the lack of consideration for complications that can arise from regular aspirin use, such as bleeding or interactions with other medications.

However, the study provides compelling mechanistic insights and builds upon the existing body of evidence supporting the potential role of aspirin in cancer prevention and metastasis inhibition.

The scientists are planning further research, including the Add-Aspirin clinical trial, which will involve over 10,000 patients with early-stage breast, colorectal, gastroesophageal, and prostate cancers across the U.K. and India. The goal of this trial is to determine whether aspirin can effectively prevent or delay cancer recurrence.

Dr. Roychoudhuri believes that aspirin may be most beneficial for patients with early-stage cancers who have undergone curative treatment but may still harbor undetected micrometastases. However, he emphasizes the need for further clinical validation before specific recommendations can be made.

Currently, low-dose aspirin or other anti-inflammatory drugs are already being considered in clinical use and in additional trials, particularly for individuals with a higher predisposition to developing colorectal, endometrial, and other cancers, such as those with Lynch syndrome.

The research received funding from various sources, including the Medical Research Council, the Wellcome Trust, and the European Research Council. The Add-Aspirin clinical trial is funded by Cancer Research UK, the National Institute for Health and Care Research, the Medical Research Council, and the Tata Memorial Foundation of India.

This study highlights the potential of aspirin, a readily available and widely used medication, to play a role in preventing cancer metastasis by modulating the immune system. While the findings are promising, it is crucial to emphasize the need for further research and careful consideration of the risks and benefits before considering aspirin therapy for cancer prevention. Patients should always consult their doctor for personalized medical advice.