Low dose of aspirin cuts recurrence risk in colorectal cancer with genetic mutation

A Swedish-led research team at Karolinska Institutet and Karolinska University Hospital has shown in a new randomized clinical trial that a low dose of the well-known medicine aspirin halves the risk of recurrence after surgery in patients with colon and rectal cancer with a certain type of genetic alteration in the tumor.

Every year, nearly two million people worldwide are diagnosed with colorectal cancer. Between 20 and 40 percent develop metastases, which makes the disease both more difficult to treat and more deadly.

Previous observational studies have suggested that aspirin may reduce the risk of certain cancers and possibly also the risk of recurrence after surgery in patients with colorectal cancer harboring mutations in genes within the PIK3 signaling pathway.

These genes regulate key cellular processes such as growth and division. When mutated, these processes can become dysregulated, leading to uncontrolled cell proliferation and cancer development. However, prior findings have been inconsistent and no randomized clinical trials had previously confirmed the association. To address this gap, the ALASCCA trial was initiated and has now been published in The New England Journal of Medicine.

The current study included more than 3,500 patients with colon and rectal cancer from 33 hospitals in Sweden, Norway, Denmark, and Finland. Patients whose tumors showed a specific genetic mutation in the PIK3 signaling pathway-a mutation found in approximately 40 percent of patients-were randomized to receive either 160 mg of aspirin daily or a placebo for three years after surgery.

For patients with the genetic mutation in PIK3, the risk of recurrence was reduced by 55 percent in those who received aspirin compared with the placebo group.

“Aspirin is being tested here in a completely new context as a precision medicine treatment. This is a clear example of how we can use genetic information to personalize treatment and at the same time save both resources and suffering,” says first author Anna Martling, professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and senior consultant surgeon at Karolinska University Hospital.

So how does aspirin reduce the risk of recurrence of colon and rectal cancer? The researchers believe that the effect is likely due to aspirin acting through several parallel mechanisms – it reduces inflammation, inhibits platelet function and tumor growth. This combination makes the environment less favorable for cancer.

Although we do not yet fully understand all the molecular links, the findings strongly support the biological rationale and suggest that the treatment may be particularly effective in genetically defined subgroups of patients.”

Anna Martling, Professor, Department of Molecular Medicine and Surgery, Karolinska Institutet

The researchers believe that the results could have global significance and influence treatment guidelines for colon and rectal cancer worldwide. Anna Martling sees the fact that the drug is well established as a major advantage.

“Aspirin is a drug that is readily available globally and extremely inexpensive compared to many modern cancer drugs, which is very positive,” says Anna Martling.

The study was funded in part by the Swedish Research Council and the Swedish Cancer Society.