Aspirin Reduces the Risk of Colorectal Cancer Recurrence

For patients with colorectal cancer, there is a promising development. In patients with PI3K mutations whose colorectal cancer had not metastasized , daily use of 160 mg aspirin after treatment was found to reduce the risk of cancer recurrence (return of the cancer) .

This important study was presented by Prof. Anna Martling and her team from the Department of Molecular Medicine and Surgery at Karolinska Institutet in Stockholm at the 2025 ASCO Gastrointestinal Cancers Symposium, #ASCOGI25.

The ALASCCA Study: The Effect of Aspirin on Cancer Recurrence

These findings came from the biomarker -based ALASCCA study, one of the first randomized clinical trials of its kind. The ALASCCA study stands out as a double-blind, randomized, multicenter, placebo-controlled study conducted at 33 hospitals in Sweden, Denmark, Finland, and Norway .

The characteristics of the 3508 patients included in the study were as follows:

• Patients with Stage II or III colon cancer or Stage I, II, or III rectal cancer were selected.
• The median patient age was 66, and 52% were women.
• Most patients were White.
• Mutations in PI3K pathway genes were detected in 1103 patients.

Patients with these mutations were divided into two groups:

• Group A: Patients with exon 9 and/or 20 mutations in the PIK3CA gene
• Group B: Patients with other PI3K pathway mutations (PIK3CA mutations outside exons 9/20 or PIK3R1/PTEN gene mutations)

Ultimately, 626 patients continued in the study and received 160 mg aspirin or placebo daily for three years.

How Common Are PI3K Signaling Pathway Mutations in Colorectal Cancer?

The PI3K (phosphoinositide 3-kinase) signaling pathway plays a critical role in cell growth, proliferation, and survival and is frequently mutated in many cancers, particularly colorectal cancer .

According to various studies, approximately 30-40% of colorectal cancers have genetic alterations affecting the PI3K signaling pathway . These mutations occur particularly in the following genes:

1. PIK3CA Mutations (15-30%)

   • The most common alterations occur in the PIK3CA gene .
   • PIK3CA mutations are particularly associated with hotspot mutations in exon 9 and exon 20 .
   • Exon 9 mutations: E542K and E545K
   • Exon 20 mutations: H1047R

2. PTEN Loss or Mutations (5-10%)

   • The PTEN (phosphatase and tensin homolog) gene is a tumor suppressor gene that inhibits the PI3K pathway.
   • PTEN loss or inactivation may cause overactivation of the PI3K/AKT/mTOR signaling pathway .

3. PIK3R1 Mutations (3-5%)

   • PIK3R1 encodes one of the regulatory subunits of PI3K.
   • These mutations generally increase PI3K activity and contribute to tumor development.

Why Are PI3K Mutations Important in Colorectal Cancer?

• Treatment Resistance: PI3K mutations are particularly associated with the development of resistance to anti-EGFR therapies (e.g., cetuximab, panitumumab). Therefore, testing for PIK3CA mutations as well as KRAS and NRAS mutationsis important when planning targeted therapy.
• Treatment with Aspirin: In patients with PI3KCA mutations, low-dose aspirin has been shown to reduce the risk of colorectal cancer recurrence (as in the ALASCCA study discussed here).
• Potential for Treatment with mTOR Inhibitors: The PI3K/AKT/mTOR pathway is a potential treatment target, and agents that inhibit this pathway (such as PI3K/mTOR inhibitors including everolimus and buparlisib) are being tested in clinical trials.

In conclusion, PI3K signaling pathway mutations occur in approximately one-third of colorectal cancer patients and may directly affect both treatment responses and treatment options.

The Study's Striking Findings

Patients taking aspirin were found to have a significantly lower risk of cancer recurrence than those receiving placebo. The key numerical findings were as follows:

• Group A (patients with exon 9/20 mutations): The risk of recurrence decreased by 51% in patients taking aspirin.

  • Recurrence rate in aspirin users: 7.7%
  • Recurrence rate in the placebo group: 14.1%

• Group B (patients with other PI3K mutations): The risk of recurrence in aspirin users decreased by 58% .

  • Recurrence rate in aspirin users: 7.7%
  • Recurrence rate in the placebo group: 16.8%

• Overall Result: When all patients with PI3K pathway mutations were considered, those taking aspirin were 55% less likely to experience cancer recurrence.

These data show that a widely used, inexpensive drug with a low adverse-effect profile, such as aspirin, could make an important difference in colorectal cancer treatment .

How Might Aspirin Have Reduced Recurrence Risk?

Aspirin is thought to have a tumor-suppressing effect in cells with PI3K mutations . Research is ongoing into whether this effect occurs through COX-2 or by directly modulating the PI3K signaling pathway.

Safety Data on Aspirin Use

With regular low-dose aspirin use, serious adverse effects were very rare :

• Severe gastrointestinal bleeding in one patient
• Brain hemorrhage in one patient
• An allergic reaction in one patient

These findings suggest that aspirin could generally be a safe treatment option.

Commentary

Toward personalized treatment with aspirin

Study leader Prof. Anna Martling said this research could represent an important turning point for colorectal cancer patients, stating:

“In this study, we showed that a widely used, well-established, inexpensive drug reduced recurrence rates and improved disease-free survival in colorectal cancer patients with PI3K mutations.”

The research also once again highlights the importance of personalized medicine and advanced genetic analyses in cancer treatment . Repurposing traditional drugs has great potential for developing new treatment strategies.

ASCO expert Dr. Pamela L. Kunz commented:

“The classic advice doctors once gave, ‘take two aspirin and call me in the morning,’ is now taking on new meaning for colorectal cancer patients. Aspirin may play an important role in reducing cancer recurrence risk in patients with genetic alterations in the PI3K signaling pathway.”

Conclusion: Aspirin Could Usher in a New Era in Colorectal Cancer Treatment

This study suggests that a widely used drug such as aspirin could reduce cancer recurrence risk in genetically defined patient groups and contribute positively to patient survival. Researchers will continue to analyze the data in greater detail and assess the effects of factors such as sex and socioeconomic status on treatment response .

These findings demonstrate how simple but effective strategies can make a major difference in colorectal cancer treatment . Aspirin use in patients identified through genetic testing could be rapidly integrated into clinical practice and improve the quality of life of many patients.