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A large randomized clinical trial led by researchers at Karolinska Institutet and Karolinska University Hospital finds that low-dose aspirin can substantially reduce the risk of colorectal cancer recurrence in patients whose tumors carry specific mutations in the PIK3 signaling pathway. The Scandinavian ALASCCA trial randomized more than 3,500 patients across 33 hospitals in Sweden, Norway, Denmark and Finland. For the subgroup whose tumors harbored the PIK3 mutation—present in roughly 40% of participants—daily 160 mg aspirin for three years after surgery lowered recurrence risk by approximately 55% compared with placebo.
A major Scandinavian trial shows aspirin slashes colon and rectal cancer recurrence risk in genetically predisposed patients. With its low cost and wide availability, it could transform cancer care on a global scale.
This result is the first definitive randomized evidence supporting aspirin as a precision adjuvant therapy for colorectal cancer, reinforcing earlier observational studies that had suggested benefit in genetically defined patient groups.
Scientific background and biological rationale
The PIK3 signaling pathway (often referred to as PI3K) is a central regulator of cell growth, metabolism and survival. Mutations in PIK3 pathway genes can dysregulate these processes and promote uncontrolled proliferation, a hallmark of cancer. Observational research previously hinted that nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin might reduce incidence and recurrence of certain cancers, particularly when tumor genetics favored sensitivity to aspirin's mechanisms.
Aspirin exerts multiple biological effects that plausibly reduce cancer progression: it lowers inflammation, irreversibly inhibits platelet activation (which can protect circulating tumor cells and support metastasis), and may directly interfere with tumor cell signaling and proliferation. The ALASCCA trial’s randomized design provides stronger causal evidence that these mechanisms translate into clinically meaningful reductions in recurrence for genetically predisposed patients.
Trial design and key findings
Participants and intervention
The ALASCCA trial enrolled over 3,500 patients who had undergone curative surgery for colon or rectal cancer. Tumor genetic testing identified patients whose tumors carried a PIK3 pathway mutation. Those with the mutation were randomized to receive either 160 mg aspirin daily or placebo, beginning after surgery and continuing for three years. Standard postoperative care and adjuvant treatments were provided according to national guidelines.
Primary outcome
Among patients with the PIK3 mutation, recurrence rates were reduced by about 55% in the aspirin arm versus placebo. The effect was statistically robust in this genetically defined subgroup; no comparable protective effect was observed across the entire unselected trial population, highlighting the importance of tumor genomics in predicting benefit.
Implications for precision medicine and global care
The study reframes aspirin—not as a one-size-fits-all preventive—but as a potential low-cost precision adjuvant therapy for colorectal cancer patients whose tumors carry specific genomic changes. Because aspirin is inexpensive and widely available worldwide, its adoption could meaningfully expand access to effective adjuvant options, particularly in resource-limited settings where newer targeted therapies are unaffordable or unavailable.
Anna Martling, the study’s first author and a professor at Karolinska Institutet, described the approach as testing “aspirin in a new precision-medicine context,” noting that genetic selection enables targeted benefit while conserving resources. The trial was published in The New England Journal of Medicine and received partial funding from the Swedish Research Council and the Swedish Cancer Society. The investigators report no conflicts of interest.
Safety considerations and clinical cautions
Low-dose aspirin is not risk-free. Common side effects include gastrointestinal irritation and an increased tendency to bleed. People with active peptic ulcer disease, certain bleeding disorders, or aspirin-exacerbated asthma should avoid aspirin unless managed carefully by clinicians. Aspirin can interact with other anticoagulants and some common medications; any adjuvant aspirin regimen should be prescribed with attention to individual patient risk factors and concomitant treatments.
Next steps and research priorities
Before routine guideline changes, clinicians and guideline committees will assess replication data, subgroup analyses, and longer-term safety. Key priorities include validating which specific PIK3 mutations predict benefit, understanding molecular mechanisms in more detail, and defining optimal aspirin dose and duration. Health systems will also need to consider implementation pathways for routine tumor genomic screening to identify eligible patients.
Expert Insight
Dr. Maya Patel, clinical oncologist and translational researcher: "These findings are exciting because they pair a simple, well-known drug with modern tumor genomics. If validated, this approach could democratize parts of cancer care—using affordable medicines where genomics indicate high likelihood of benefit. The next steps should be rapid replication and careful protocols to manage bleeding risk while maximizing cancer control."
Conclusion
The ALASCCA randomized trial provides the strongest evidence to date that low-dose aspirin can halve colorectal cancer recurrence in patients with PIK3 pathway mutations. The result highlights the power of combining routine tumor genomics with inexpensive, widely available therapies to create scalable precision-medicine strategies. Future work should confirm predictive genomic markers, refine dosing and safety protocols, and explore implementation models so that eligible patients worldwide can benefit safely.
Source: sciencedaily
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