Some treatments can save a life now, but lead to risks later on. For example, heart disease can be an unfortunate side effect of certain kinds of chemotherapy, particularly those known as anthracyclines. For children with cancer, the effects often emerge in adulthood.

Fortunately, researchers are aware of the risk, and City of Hope scientists are doing something about it.

Smita Bhatia led a study with implications for future cancer treatment options. (Photo by Darrin S. Joy)

Their work marks a major move toward customizing cancer treatment for children based on their genetic makeup. The aim: to reduce the risk of therapy-related heart disease later in life.

To figure out how to do that, researchers first needed to understand better the factors that increase a cancer patient’s risk of developing long-term heart problems.

Smita Bhatia, M.D., M.P.H., Ruth Ziegler Chair in Population Sciences and director of the Center for Cancer Survivorship, recently led a study of nearly 500 childhood cancer survivors, looking to pin down those factors.

They found that the amount of chemotherapy a patient received during treatment is important; the higher the dose of anthracyclines, the higher the risk of heart failure.

But they also found that common mutations or variations in two genes play a role. Patients with certain forms of the carbonyl reductase 1 and 3 genes, also known as CBR1 and CBR3, had an increased risk of heart damage when taking the chemotherapy drugs, regardless of the dosage.

These two genes help break down anthracyclines into other compounds that can damage heart muscle. Variations in the genes may cause larger-than-normal amounts of those compounds to collect in the heart.

With these findings in mind, the research team suggested that physicians in the future may consider altering treatment plans for certain pediatric cancer patients who carry the specific forms of CBR1 and CBR3.

Heart disease is one of many long-term health issues that survivors of childhood cancers may face after their cancer is cured. Anthracyclines are standard therapy for 50 to 60 percent of childhood cancer patients.

The City of Hope study also showed that gender matters. Girls in the study had a 65 percent higher risk of heart problems due to anthracyclines. And patients whose hearts were exposed to radiation during therapy were at three times higher risk than others.

“Based on our findings and additional studies, we can develop a personalized approach to treatment that addresses the genetic and medical factors that may impact our patients,” said Bhatia. She hopes to begin clinical trials within a few years that would test a heart-protecting drug or different chemotherapy treatments.