New Method Helps Predict Patient Response to Chemotherapy
According to new research from Northwestern Medicine, reprogrammed stem cells can be used to identify patients who are likely to experience a dangerous side effect of a common chemotherapy drug.
The medication, Doxorubicin, also known Adriamycin, effectively treats a wide range of cancers, including breast cancer and pediatric leukemia. But for about eight percent of patients, the drug causes cardiotoxicity – heart muscle damage so severe that it can lead to heart failure. Currently, healthcare providers can’t predict in advance who will fall into this subset of patients.
“We were interested in whether there is a genetic reason for why some patients experience cardiotoxicity and some do not,” said Paul Burridge, PhD, assistant professor of Pharmacology at Northwestern University Feinberg School of Medicine and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
Turning Stem Cells into Heart Cells, Heart Cells into Insights
It’s difficult to isolate and grow a patient’s heart cells in a lab, so Burridge took an alternative route to test the drug: stem cells. First, Burridge and scientists at Stanford University acquired skin cells from patients with breast cancer who were treated with doxorubicin – some with cardiotoxicity and some without it. The investigators reprogrammed the skin cells into pluripotent stem cells, which can become many different types of cells.
“We then turned these stem cells into heart muscle cells, treated them with doxorubicin and measured their responses,” Burridge explained. “Our results showed that heart cells from patients who have cardiotoxicity were significantly more sensitive to doxorubicin-induced toxicity. They had more structural damage, reduced contraction, DNA damage and died more easily.”
By analyzing gene expression in the cells, the scientists were able to establish genetic differences in drug response. Their work also suggests that mitochondrial dysfunction could be behind the toxic side effect.
The study’s findings also have implications for clinical care.
“This project proves for the first time that we might be able to predict the likelihood of a patient experiencing doxorubicin-induced cardiotoxicity by looking at the patient’s DNA,” Burridge said. “This patient could then be given an alternative chemotherapy drug or a lower dose. In contrast, patients who are likely to be resistant to doxorubicin-induced cardiotoxicity might be able to be given a higher dose and have a better chance of success with their chemotherapy.”