5 Minutes
A large randomized clinical trial led by Karolinska Institutet and Karolinska University Hospital indicates that a low, daily dose of aspirin may dramatically reduce the risk of colorectal cancer recurrence in a genetically defined subgroup of patients. The study — published in The New England Journal of Medicine as the ALASCCA trial — enrolled more than 3,500 patients with colon or rectal cancer across 33 hospitals in Sweden, Norway, Denmark and Finland. Early results show a roughly 55% reduction in recurrence for patients whose tumors carry mutations in the PIK3 signaling pathway when treated with 160 mg of aspirin daily for three years following surgery.
Trial design and key findings
The ALASCCA trial stratified participants by tumor genetics and randomized those with PIK3 pathway alterations (present in about 40% of colorectal cancers) to receive either 160 mg of aspirin daily or a placebo for three years after curative-intent surgery. The primary endpoint was cancer recurrence. In patients whose tumors harbored PIK3 pathway mutations, aspirin use was associated with a 55% lower risk of recurrence compared with placebo.
The trial enrolled over 3,500 patients at 33 Nordic hospitals and is the first randomized clinical trial to demonstrate a genotype-specific benefit for aspirin in colorectal cancer recurrence prevention. These results convert earlier observational signals into randomized evidence and mark an important step in precision oncology for colorectal cancer.
Scientific background: PIK3 pathway and colorectal cancer
The PIK3 signaling pathway regulates fundamental cell functions including growth, proliferation and survival. Mutations that activate PIK3-related genes can drive uncontrolled cellular growth and promote tumor progression. Observational cohort studies had previously suggested that aspirin might lower colorectal cancer incidence or recurrence, particularly in tumors with PIK3 pathway alterations, but randomized evidence was lacking until ALASCCA.
By testing aspirin in a genetically defined subgroup, ALASCCA applies the principles of precision medicine: matching a low-cost, widely available therapy to patients whose tumor biology indicates the greatest likely benefit.
How aspirin may reduce recurrence
Researchers propose multiple, complementary mechanisms for aspirin’s anticancer effect. Aspirin is a well-known anti-inflammatory and an inhibitor of platelet aggregation; both activities may reduce the ability of circulating tumor cells to seed metastases and may blunt tumor-promoting inflammation in the microenvironment. Aspirin may also exert direct effects on tumor cell signaling pathways that intersect with PIK3-driven biology. While the precise molecular cascades remain an active area of research, the combined anti-inflammatory, anti-platelet and potential anti-proliferative effects provide a plausible biological rationale for the observed clinical benefit.
Implications for clinical practice and public health
If replicated and adopted into guidelines, the ALASCCA findings could change postoperative management for a substantial fraction of colorectal cancer patients worldwide. Key advantages of aspirin include its global availability, low cost and extensive safety data in other contexts. That said, implementation would require routine tumor genetic testing to identify PIK3 pathway alterations and careful consideration of aspirin’s known risks (for example, gastrointestinal bleeding) on a per-patient basis.
Because between 20% and 40% of colorectal cancer patients currently develop metastatic disease, a low-cost intervention that halves recurrence risk in the right patients could produce meaningful improvements in survival and reduce both treatment costs and patient morbidity in many health systems.
Expert Insight
"This trial is an excellent example of repurposing an old, inexpensive drug using modern genetic selection," says Dr. Eleanor Finch, a fictional clinical oncologist and science communicator. "The magnitude of benefit in the PIK3-mutant subgroup is striking, but implementation will hinge on widespread access to tumor genotyping and clear clinical pathways to manage bleeding risk."
Conclusion
The ALASCCA randomized trial provides the strongest evidence to date that low-dose aspirin can substantially reduce colorectal cancer recurrence in patients whose tumors harbor PIK3 pathway mutations. The results illustrate how combining tumor genomics with repurposed drugs can yield effective, affordable precision therapies. Future steps include confirming long-term survival benefits, formal guideline review, and expanded testing to identify eligible patients safely and equitably.
Source: scitechdaily
Leave a Comment