A common over-the-counter medication, aspirin, has long been used to treat pain, fever, and thin the blood. Now, new research suggests that taking low doses of aspirin daily after colon surgery could help prevent the return of cancer in some patients. This discovery could open a low-cost way to fight colorectal cancer, especially for those with a specific type of tumor. A study led by Anna Martling at the Karolinska Institutet found that taking a daily low-dose aspirin pill can reduce the risk of cancer returning by more than half in certain patients. The results of this trial, published in September 2025 in the New England Journal of Medicine, showed that the benefit applies specifically to patients whose tumors have a particular genetic anomaly. This anomaly has long lacked an affordable targeted treatment. The trial, named ALASCCA, involved more than 3,500 patients who had surgery for colorectal cancer in 33 hospitals across Sweden, Norway, Denmark, and Finland. After their operations, all patients feared the possibility of cancer returning. Following analysis of each tumor, 626 patients with the specific genetic mutation were randomly assigned to take either 160 milligrams of aspirin daily or a placebo for three years. At the end of the follow-up period, cancer recurrence was significantly lower in the group that took aspirin. Among patients with the most common mutation, 7.7% experienced a relapse while taking aspirin, compared to 14.1% who took a placebo. For other mutations in the same pathway, the difference was even greater, with 7.7% relapse under aspirin versus 16.8% under placebo. Disease-free survival after three years also improved, with up to ten percentage points of advantage in the most responsive group. This means the risk of cancer returning is cut in half, a rare outcome with such a common drug. The protective effect of aspirin is due to its ability to reduce inflammation and slow the activity of blood platelets. These actions deprive cancer cells of growth signals and hinder the formation of micro-clots that help cancer cells spread. This explains why a painkiller like aspirin can help delay the return of the disease. However, only patients whose tumors have a specific genetic mutation in the PI3K (phosphoinositide 3-kinase) pathway respond to the treatment. This pathway is involved in controlling cell division and is often overactivated in cancer, allowing it to grow more quickly. Nearly 40% of colorectal cancers have this defect. Identifying the right tumors is crucial, as taking aspirin for patients who do not have this mutation would be unnecessary and could lead to side effects like bleeding, the main risk of aspirin. The trial recorded more serious adverse effects in the aspirin group, with 57 cases compared to 38 in the placebo group. The researchers suggest that checking for these genetic mutations should become part of the standard assessment after cancer surgery, a practice already used for other cancers. Since aspirin is inexpensive and available worldwide, it could help prevent cancer recurrence in thousands of patients. Researchers are now investigating whether the same drug might also help prevent cancer recurrence in other types of tumors with similar genetic issues.