By Karen Angelo
Doxorubicin, a chemotherapy drug that’s been widely used for more than 50 years, is effective in treating certain cancers in about 80% of adult patients. But for the remaining 20% of adults who receive it, the drug can cause heart failure. The results are more concerning for children, with 57% of those treated with doxorubicin experiencing cardiac dysfunction.
Research by Assoc. Prof. Jonghan Kim of the Department of Biomedical and Nutritional Sciences in the Zuckerberg College of Health Sciences may help change that. Kim was recently awarded a $1.2 million grant from the National Heart, Lung and Blood Institute for a study that will help to better predict the impact of doxorubicin on cancer patients’ hearts.
His research is part of a larger $3.7 million, five-year study led by Dr. Aarti Asnani of the Beth Israel Deaconess Medical Center.
“We know that for some patients, doxorubicin accumulates in the heart, killing a portion of it, and therefore we want to identify this possibility during the early stage of treatment,” says Kim.
By developing a biomarker on how a patient’s heart will respond to doxorubicin, the research results can provide oncologists with new data that will indicate timely interventions such as lowering the dosage, switching to another treatment or adding medications that protect the heart. The results will also allow for more intensive and effective cancer treatments in patients who are at low risk for cardiac toxicity.
Kim plans on developing and characterizing the predictive biomarker by analyzing hemopexin, a plasma protein in the blood that binds to circulating heme, an iron-containing molecule, with very high binding affinity.
“Hemopexin is a good protein because it gets rid of heme that is toxic,” says Kim. “The body typically senses the level of heme and makes more hemopexin when there is too much heme. It’s interesting that hemopexin can also tell us about doxorubicin toxicity, so that we can predict the risk of heart failure.”
As the principal investigator on two other National Institutes of Health (NIH) R01 grants, Kim is researching new therapeutic strategies to solve problems in iron- and heme-related disorders that can lead to cardiovascular, hematologic and neurological diseases.
He also recently received another $430,000 NIH R21 grant that will support a novel therapeutic approach for Friedreich’s ataxia, an inherited neurodegenerative movement disorder, by modulating iron transport across the mitochondria, the powerhouse of the cell.