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New Mechanism for Aspirin’s Role in Cancer Prevention


It has been known for a while that aspirin has the properties to reduce the risk of colorectal cancer as well as some other cancers. However, there are certain risks associated with its intake like in some cases vehement gastrointestinal bleeding which makes it compulsory to understand how aspirin acts at low doses before it can be prescribed generally as a preventive.


Cornelia Ulrich, PhD, Senior Director of Population Sciences at Huntsman Cancer Institute in Salt Lake City remarked that in the long run the aim is to personalize prevention with aspirin because like everything it can have side effects. The need is to find a tailored solution for people who are most likely to benefit and have the lowest risk of adverse outcomes.

The results of the study were published in the journal of Cancer Epidemiology, Biomarkers, and Prevention. In this study Ulrich and her fellow researchers used an innovative technique, metabolite profiling, to identify a biochemical pathway previously unknown to be regulated by aspirin. It was found by the researchers that aspirin significantly decreases the level of a chemical called 2-hydroxyglutarate in the blood of healthy volunteers and in two colorectal cancer cell lines. It is understood that 2-hydroxyglutarate is a driver of cancer development as increased levels have been found in certain cancers of the blood and brain. There are several ongoing studies that are exploring its ability as a molecule that promotes tumor formation.


Ulrich is very positive about the new study and points out that the study has revealed many evidences that aspirin has a significant role to play in cancer prevention. It does point to a new pathway that needs to be studied further in the context of aspirin.

As a part of the study, the metabolic profiles from the blood of 40 individuals who had taken aspirin for 60 days were studied comprehensively. The design was rigorous; each participant had a phase with and without aspirin. Ulrich remarked that more than 360 metabolites, or small molecule chemicals such as sugars, amino acids, and vitamins, were analyzed. In short, study almost covered most of the known biochemical pathways in the body.

On analyzing the data, it was found that aspirin metabolites were increased in the volunteers as expected (p<0.001), but statistically significant changes were also noted in a metabolite that has been found to drive cancer development, 2-hydroxyglutarate, which was reduced by 12% (p=0.005). In order to follow-up the finding further, the researchers evaluated the levels of 2-hydroxyglutarate in cultured cancer cells after treatment with aspirin in the laboratory. Consistent reductions in 2-hydroxyglutarate, up to 34% was seen in the colorectal cells lines. It was also discovered that the primary metabolite of aspirin, called salicylate, inhibits an enzyme called HOT (hydroxyacidic-oxoacid transhydrogenase) that triggers the production of 2-hydroxyglutarate, which suggests that aspirin is acting on a previously unknown pathway at a concentration comparable to that of individuals treated with aspirin.

Previous studies on the anti-cancer role of aspirin explored its anti-inflammatory and anti-clotting roles as the possible reasons for the cancer-preventive effects. But, this study shows the evidence that other pathways are also involved, particularly at lower aspirin doses.

Ulrich opined that this study suggests that aspirin is playing a key role in interrupting multiple pathways that are linked to cancer development. This study has shed light on evidences that a reduction in 2-hydroxyglutarate may identify a new mechanism for aspirin in cancer prevention. She added that further studies are needed to determine whether the changes in 2-hydroyglutarate levels after aspirin treatment, observed in blood plasma and cultured cancer cells, are also present in colon tissue.