Aspirin Use in Colorectal Cancer With PI3K Mutations
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on October 6th, 2025
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Aspirin, a widely used analgesic and anti-inflammatory agent, reduces inflammation by inhibiting cyclooxygenase-2 (COX-2). Colorectal cancer tumors often overexpress COX-2, which activates the phosphatidylinositol 3-kinase (PI3K) pathway and promotes tumorigenesis. Supported by the Swedish Research Council, researchers conducted a study to evaluate whether aspirin could improve outcomes in patients with colorectal cancer harboring PI3K pathway mutations.
The trial enrolled 626 patients with a median age of 66 years who had undergone surgical resection for colon or rectal cancer with lymph node involvement. All participants carried PI3K pathway mutations, with roughly half presenting mutations in exon 9 or 20, while the remainder had alterations in other related genes (PIK3CA, PIK3R1, or PTEN). Patients were randomized to receive either placebo or 160 mg of aspirin daily.
After three years of treatment, daily aspirin use reduced the risk of colorectal cancer recurrence by more than 50%, with benefit observed across all PI3K mutation subtypes. Notably, the protective effect was more pronounced in female patients, whereas outcomes in men did not differ between aspirin and placebo groups. The authors found no sex-based differences in adherence or body weight, suggesting other biological mechanisms at play. They also highlighted that aspirin’s antitumor activity may extend beyond PI3K inhibition, with its antiplatelet effects potentially enhancing immune clearance of circulating tumor cells.
The trial enrolled 626 patients with a median age of 66 years who had undergone surgical resection for colon or rectal cancer with lymph node involvement. All participants carried PI3K pathway mutations, with roughly half presenting mutations in exon 9 or 20, while the remainder had alterations in other related genes (PIK3CA, PIK3R1, or PTEN). Patients were randomized to receive either placebo or 160 mg of aspirin daily.
After three years of treatment, daily aspirin use reduced the risk of colorectal cancer recurrence by more than 50%, with benefit observed across all PI3K mutation subtypes. Notably, the protective effect was more pronounced in female patients, whereas outcomes in men did not differ between aspirin and placebo groups. The authors found no sex-based differences in adherence or body weight, suggesting other biological mechanisms at play. They also highlighted that aspirin’s antitumor activity may extend beyond PI3K inhibition, with its antiplatelet effects potentially enhancing immune clearance of circulating tumor cells.