Aspirin’s Evolving Role in Cancer Prevention and Outcomes

Aspirin (Bayer), the century-old analgesic and antiplatelet agent, is generally known for its cardiovascular benefits. However, a growing body of evidence is indicating that its effect could be broader, especially concerning cancer prevention and patients’ survival. While investigators are still working on unraveling the observational and clinical data that span over several decades, clinicians and pharmacists alike are tasked with understanding both the promise and limitations of aspirin in oncology care and cancer risk management.

Epidemiological Evidence: Aspirin and Long-Term Cancer Risk

A thorough 20-year cohort study published in the Journal of the National Cancer Institute investigated the connection between long-term aspirin use and the occurrence of cancer of various types. Out of the more than 1.9 million individuals who were monitored for a period of up to 20 years, regularly taking low-dose aspirin (75, 150 mg) did not drastically reduce the overall risk of cancer; however, detailed analyses on specific locations of the body showed that risk ratios for the colon, rectum, esophagus, stomach, liver, pancreas, and other parts of the gastrointestinal tract, as well as systemic ones, were lowered by 10% or more.¹

These findings are consistent with previous observational data that showed that use of aspirin on a regular basis is associated with a lower colorectal cancer risk and a lesser chance of recurrence, particularly among those at high risk of colorectal cancer, for instance, patients with hereditary cancer syndromes like Lynch Syndrome.² In fact, daily treatment with aspirin in higher doses has been linked to a markedly lower risk of colorectal cancer in the long term in patients with Lynch Syndrome, with divergence in the risk usually appearing after a few years of use.³

Biological Mechanisms: Beyond Pain Relief

The potential anticancer effects of aspirin are based on various biological mechanisms, a considerable number of which remain separate from the drug's platelet aggregation and anti-inflammatory properties. The drug inhibits cyclooxygenase (COX) enzymes, mainly COX-2, in an irreversible way, therefore leading to reduced production of prostaglandins, which are involved in tumor cell proliferation and new blood vessel formation.⁴

Preclinical and epidemiological studies have highlighted the overexpression of COX-2 in different types of cancers and have associated the drug's downregulation with the decreased risk of tumor initiation and progression.⁵

New mechanistic studies are indicating that aspirin may have an effect on cancer metastasis through the reduction of platelet activation and the suppression of mechanisms that allow circulating tumor cells to escape immune surveillance. It has been suggested that the inhibition of platelet-released factors like thromboxane A2 could boost T-cell-mediated immune responses to cancer cells spreading, providing a reasonable interpretation for the lowered occurrence of metastases.⁶

Clinical Implications: Survival and Recurrence

Besides cancer risk reduction, aspirin has also been positioned as a beneficial agent in improving cancer outcomes after a diagnosis, which has attracted substantial attention. Meta-analyses of observational studies have shown that aspirin use is continually linked with better survival and less metastatic spread in a variety of cancers.⁷ These correlations could be the result of tumor-intrinsic effects as well as aspirin’s influence on the tumor microenvironment.

For colorectal cancer patients, there is a growing body of evidence that supports the use of daily low-dose aspirin not only to reduce the chance of relapse but also to enhance prolonged survival without the disease, particularly in tumors with certain molecular characteristics like PIK3CA mutations. Some prospective cohort studies and secondary analyses of trials have reported that recurrence rates among aspirin users are up to 55% lower as compared to nonusers; however, randomized control trials are needed to verify these findings.⁸

Balancing Benefits and Risks

Despite compelling data, the use of aspirin as a universal cancer preventive agent is still a matter of debate. Large, randomized trials such as the Aspirin in Reducing Events in the Elderly (ASPREE) study (NCT01038583) showed no beneficial effect of low-dose aspirin on overall cancer incidence in older adults and even suggested that cancer-related mortality may have been increased in some participants.⁹ These divergent outcomes reflect the heterogeneity of the evidence and underscore the necessity of individualized patient assessment.

Long-term aspirin use is known to have side effects such as gastrointestinal bleeding and hemorrhagic stroke, which need to be taken into consideration along with anticancer benefits, particularly in populations without compelling cardiovascular indications.

Conclusions and Future Directions

Aspirin’s role in cancer prevention and survival continues to evolve, supported by a mix of epidemiological, mechanistic, and clinical data. Long-term use appears to confer modest reductions in site-specific cancer risk and may improve outcomes for certain patients, particularly in colorectal cancer. Yet evidence remains inconsistent across cancer types and age groups. Clinicians should engage in shared decision-making with patients, considering individual risk factors, cancer history, and bleeding risks when contemplating aspirin therapy beyond cardiovascular indications. Future randomized trials and molecularly stratified research will be critical to clarifying aspirin’s place in cancer prevention and adjunctive therapy.

REFERENCES

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8. Can Aspirin Help Reduce Your Cancer Risk. American Cancer Society. Published February 19, 2025. Accessed February 11, 2026. https://www.cancer.org/cancer/latest-news/can-aspirin-help-reduce-your-cancer-risk.html

9. Orchard SG, Polekhina G, Zalcberg J, et al. Cancer Incidence and Mortality With Aspirin in Older Adults: Follow-Up of the ASPREE Trial. JAMA Oncol. Published online January 29, 2026. doi:10.1001/jamaoncol.2025.6196