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Recent research has revealed insights into how aspirin may contribute to reducing cancer metastasis by activating the immune system, with significant funding from the Medical Research Council.
Published in Nature, the study highlights that understanding this mechanism can bolster ongoing clinical trials, potentially allowing for the strategic use of aspirin in preventing the spread of certain cancers and fostering the development of more effective therapies to combat metastasis.
The researchers emphasize the necessity of caution, noting that aspirin can induce serious side effects in some individuals. Hence, clinical trials are crucial to ascertain the safest and most effective methods for its use in preventing the spread of cancer, and individuals are advised to consult their healthcare provider prior to starting aspirin therapy.
Previous investigations into cancer patients have shown that daily low-dose aspirin usage correlates with a lower likelihood of metastasis in certain cancers, including breast, colorectal, and prostate cancer, prompting further clinical studies. However, the precise workings of how aspirin inhibits metastasis had not been fully understood until this study.
The investigation was led by scientists at the University of Cambridge, who described their discovery as a fortuitous outcome while examining the mechanics of metastasis. As cancer typically originates in a specific site, it is noteworthy that 90% of cancer-related deaths arise from the disease spreading to other regions of the body.
Researchers aimed to decode how the immune system reacts to metastatic cells, as these individual cancer cells are particularly susceptible to immune responses when they detach from the primary tumor. Unlike cancer cells situated within larger tumors that may develop immune-suppressive environments, solitary cancer cells can be more effectively recognized and eliminated by the immune system.
In their analysis, the team screened 810 genes in murine models and identified 15 genes that influenced cancer metastasis. Notably, they discovered that mice deficient in a gene encoding the protein ARHGEF1 displayed a reduced incidence of metastasis from several primary cancers to the lungs and liver.
The researchers found that ARHGEF1 plays a role in inhibiting T cells—immune cells crucial for detecting and destroying metastatic cancer cells. To utilize this discovery for therapeutic purposes, they needed to pinpoint a method for drugs to effectively target this protein. Their investigation revealed that ARHGEF1 is activated by thromboxane A2 (TXA2), a clotting factor that T cells encounter.
This connection was surprising to the researchers, as TXA2’s relationship with aspirin is already well-documented. TXA2 is produced by platelets, which assist in the clotting process but can also be implicated in adverse cardiovascular events like heart attacks and strokes. Aspirin’s role in diminishing TXA2 production underlies its well-known protective effects against such conditions.
The current study elucidates that aspirin inhibits the spread of cancer by lowering TXA2 levels, thereby relieving T cells from suppression. Using a murine melanoma model, the researchers demonstrated that the presence of aspirin led to a significant reduction in metastatic occurrences compared to control subjects, emphasizing that this effect hinges on the release of T cells from TXA2’s suppressive influence.
Professor Rahul Roychoudhuri of the University of Cambridge, who spearheaded the research, remarked on the challenge of early-stage cancers, noting that while treatments such as surgical removal can be effective, many patients ultimately face relapse due to the emergence of dormant micrometastases—cancer cells that have already disseminated. He emphasized that the initial phase of cancer spread presents a unique opportunity for treatment, as these cells are particularly vulnerable to immune attack.
Dr. Jie Yang, a researcher involved in the study, described the moment of discovery regarding TXA2 as transformative, altering the course of their inquiry into aspirin’s anti-metastatic actions. The findings suggest that aspirin or similar medications targeting this pathway could offer a cost-effective alternative to more expensive antibody therapies, enhancing global accessibility.
Looking ahead, the research team plans to collaborate with Professor Ruth Langley from the MRC Clinical Trials Unit at University College London, who leads the Add-Aspirin clinical trial aimed at evaluating aspirin’s potential in preventing the recurrence of early-stage cancers. Professor Langley, who was not part of this study, acknowledged its significance in contextualizing ongoing trials and identifying patients who would benefit most from aspirin following a cancer diagnosis.
While aspirin can indeed lead to severe adverse effects for a small subset of individuals, such as gastrointestinal bleeding or ulcers, understanding which cancer patients might reap the benefits of aspirin is crucial. It remains essential for individuals to engage with their doctors before initiating aspirin regimens.
The research received primary funding from the Medical Research Council, along with additional support from the Wellcome Trust and the European Research Council. The Add-Aspirin clinical trial is supported by Cancer Research UK, the National Institute for Health and Care Research, the Medical Research Council, and the Tata Memorial Foundation of India.
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