A groundbreaking study has revealed the mechanism by which aspirin can inhibit the spread of certain cancers through immune system stimulation. Researchers from the University of Cambridge, primarily funded by the Medical Research Council, have published their findings in Nature. This discovery not only supports ongoing clinical trials but also paves the way for targeted aspirin usage to prevent cancer metastasis and the development of more effective drugs. While aspirin shows promise, scientists caution that it can have serious side effects in some individuals, emphasizing the need for further research and consultation with healthcare providers before use.

The journey to this discovery began with an investigation into how cancer spreads from its initial site to other parts of the body—a process known as metastasis. The researchers aimed to understand the immune system's response during this critical phase, particularly focusing on how isolated cancer cells are more vulnerable to immune attacks compared to those within larger tumors. By screening 810 genes in mice, they identified 15 that influenced metastasis. One gene stood out: ARHGEF1. Mice lacking this gene showed reduced metastasis of various primary cancers to the lungs and liver. Further analysis revealed that ARHGEF1 suppresses T cells, a type of immune cell crucial for recognizing and destroying metastatic cancer cells.

The breakthrough came when researchers traced cellular signals and discovered that ARHGEF1 is activated by thromboxane A2 (TXA2), a clotting factor produced by platelets. TXA2, already well-known for its role in aspirin's anti-clotting effects, was unexpectedly found to play a part in suppressing T cells. This revelation led to the understanding that aspirin, by reducing TXA2 production, can release T cells from suppression, thereby preventing cancer metastasis. In mouse models of melanoma, aspirin treatment significantly decreased the frequency of metastases compared to control groups.

Professor Rahul Roychoudhuri from the University of Cambridge highlighted the therapeutic window of opportunity when cancer first spreads, noting that cancer cells are particularly vulnerable to immune attack during this period. Dr. Jie Yang, who conducted the research, described the moment of realization about TXA2's role as a "Eureka moment," leading to a new path of inquiry. Aspirin's potential as a less expensive therapy could make it more accessible globally compared to antibody-based treatments.

Looking ahead, the researchers plan to collaborate with Professor Ruth Langley from the MRC Clinical Trials Unit at University College London to translate these findings into clinical practice. The Add-Aspirin trial aims to determine if aspirin can stop or delay early-stage cancers from recurring. Professor Langley emphasized the importance of identifying patients most likely to benefit from aspirin while considering its potential side effects. This research opens new avenues for preventing cancer recurrence and improving patient outcomes.