Aspirin Treatment May Benefit Certain Colorectal Cancer Patients

Treatment with aspirin was found to inhibit growth of colorectal cancer in patients whose tumors were characterized by a mutation in the PIK3CA gene.

Previous experimental evidence implied that inhibition of the enzyme prostaglandin-endoperoxide synthase 2 (PTGS2) (also known as cyclooxygenase-2) by aspirin down-regulated phosphatidylinositol 3-kinase (PI3K) signaling activity and inhibited growth of colorectal cancer. In the current study investigators at Harvard Medical School (Boston, MA, USA) found that the positive the effect of aspirin on survival and prognosis in patients with cancers characterized by mutated PIK3CA (the phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit alpha polypeptide gene) differed from the effect among those with wild-type PIK3CA cancers.

The investigators evaluated data on 964 rectal or colon cancer patients that included data on aspirin use after diagnosis and the presence or absence of PIK3CA mutation. Furthermore, they examined tumor markers, including PTGS2, phosphorylated AKT, KRAS, BRAF, microsatellite instability, CpG island methylator phenotype, and methylation of long interspersed nucleotide element 1.

They reported in the October 25, 2012, issue of the New England Journal of Medicine (NEJM) that the use of aspirin after diagnosis in patients with the gene mutation was associated with a 46% reduction in overall mortality and an 82% reduction in colorectal cancer-specific mortality. In contrast, aspirin use in patients without the mutation did not affect either overall or colorectal-specific mortality.

Approximately 17% of patients with colorectal cancer have a tumor that carries a mutated PIK3CA gene, so aspirin treatment could potentially benefit nearly 24,000 of the 140,000 Americans that are diagnosed with colorectal cancer each year.

On the other hand, the investigators cautioned that in the current study only 66 patients with the PIK3CA mutation used aspirin after being diagnosed with colorectal cancer and only three of them died of colorectal cancer during the follow-up period. Therefore, despite the promising nature of the results, they have to be considered as preliminary, and larger prospective studies need to be conducted.

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