Pharmacogenomics of anthracycline-induced cardiotoxicity in childhood

Serious adverse drug reactions (ADRs) are the fourth leading cause of death and illness in the developed world, claiming many lives and costing billions of dollars each year. Children are especially at risk for ADRs: an estimated 15 per cent of all children admitted to hospitals get ADRs. Although many factors influence the effect of drugs, such as age, weight and organ function, genetic factors account for a great proportion. Small genetic differences between patients can cause serious ADRs. One group of drugs, called anthracyclines, are an effective treatment for many children and adults with cancer. However, they can sometimes be very harmful or damaging to the heart (cardiotoxicity), resulting in life-long drug treatment, the need for heart transplantation, or death. Dr. Henk Visscher is working to find the genetic factors behind this phenomenon. He is comparing gene variants between children who have experienced severe cardiotoxicity after receiving anthracyclines with children who did not. Using high-tech machines, he can screen for thousands of gene variants at the same time, making it more likely to find the gene(s) involved. Once identified, he will conduct a number of studies to confirm that the identified gene variants are the “culprits.” Visscher plans to create a diagnostic test based on the variants that can predict cardiotoxicity in patients taking anthracyclines. This would enable physicians to identify at-risk patients before they take the drugs, allowing them to adjust the dose, choose a different drug or monitor a high-risk patient more closely. Ultimately, this may help prevent potentially fatal heart disease among cancer survivors.