‘An aspirin a day keeps the doctor away’
There have been conflicting views over the effects of aspirin over its more than 100 year reign as a diverse cure all to pain relief and preventative of heart disease and some cancers. Its mechanism for pain relief has long been proven by its ability to block the COX-1 enzyme, involved in inflammation and blood clotting. While this makes sense for pain relief, how does this associate with cardiovascular disease and cancer?
A new approach from a team of scientists at Duke Health, led by Deepak Voora, M.D., assistant professor in Duke’s Center for Applied Genomics & Precision Medicine, can evaluate specific drug actions using genomic data, providing the team with an explanation of mechanisms of drug activity in the body. The team created an aspirin response signature (ARS) that allowed them to examine gene activity patterns in blood upon aspirin exposure. The ARS was developed using blood gene expression profiling methods before and after aspirin exposure in a set of healthy volunteers and validating the signature in a separate set of healthy and diseased patients.
The ARS consists of a network of 62 co-expressed transcripts associated with aspirin’s effects on platelet function and myocardial infarction. This gene network contained one commonality: regulation by RUNX1, a key regulator of genes controlling platelet and megakaryocyte function. The team discovered that aspirin can regulate RUNX1 gene expression, affecting associated platelet proteins. Up regulation of RUNX1 in blood is associated with decreased risk of death and heart attack in cardiovascular disease patients. RUNX1 is also a tumor suppressor correlated with increased survival rates in colon cancer patients.
Not only did the approach taken in this study shed additional light on aspirin’s specific mechanisms, it also provides a new way of thinking about how to look at drug activity using genomic profiling.
“This approach to comprehensively evaluate the actions of a drug using genomic data -- as we have done here with aspirin -- is a paradigm shift that could change how drugs are developed and positioned for clinical use, said co-author Geoffrey Ginsburg, M.D., director of the Center for Applied Genomics & Precision Medicine.
It turns out that aspirin’s diverse effects on several diseases are due to its ability to regulate gene expression of a common regulator. So, depending on your health, an aspirin a day might indeed keep the doctor away.
Sources: Duke Medicine