Kasey Leger, MD
Evaluation of microRNAs as novel markers of cardiotoxicity in children undergoing anthracycline therapy for pediatric cancer
The battle against pediatric cancer is one of the greatest success stories in medicine. Once considered uniformly fatal, now nearly 80% of children diagnosed with cancer will be long-term survivors. Despite these remarkable strides, the cost of cure is high. Seventy percent of childhood cancer survivors have at least one chronic medical condition that can be attributed to their initial cancer or its therapy. Nearly half of these conditions are considered severe
Cardiomyopathy is a form of progressive heart failure that can result from treatment with certain types of chemotherapy. The most common of these is a class of medications called anthracyclines, which are often essential to bringing cancer cure. Heart disease is one of the most common causes of treatment-related death in our survivor population. Within twenty years of exposure to anthracycline chemotherapy up to 15% of childhood cancer survivors will develop congestive heart failure, resulting in a heart transplant or death.
Often treatment-related heart disease progresses without symptoms for years, thus heart damage goes unnoticed until it is too late. Currently, we lack effective screening tools that allow for early detection and diagnosis of children with subclinical heart disease. My goal is to develop a tool that predicts the risk for developing life-threatening heart disease among children treated with anthracyclines. A novel tool that allows the diagnosis of heart disease before patients have symptoms could allow for intervention before permanent damage ensues.
MicroRNAs are recently discovered molecules that regulate the body's normal functioning and response to stress and disease. Specific microRNAs, detected in the blood, have shown great potential as sensitive markers for the diagnosis of heart attacks and other forms of heart disease.
My research will evaluate changes in circulating microRNAs in children undergoing anthracycline chemotherapy, as well as childhood cancer survivors who suffer from an anthracycline-related cardiomyopathy. I hypothesize that characterizing microRNA levels following anthracycline-induced heart injury will aid in the early diagnosis of children at risk for serious heart disease and allow for early intervention. Further, I hypothesize that survivors with an advanced anthracycline-induced cardiomyopathy will demonstrate a unique microRNA profile that could provide insight into why cardiac damage is occurring. This project is an exciting first step towards using microRNAs to diagnose and treat chemotherapy–induced heart damage- an approach that could eventually ameliorate the burden of heart disease suffered by childhood cancer survivors.
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