A new Northwestern Medicine study published in Nature Medicine has shown that reprogrammed stem cells can be used to identify patients with cancer who are likely to experience a dangerous side effect of a common chemotherapy drug.
Doxorubicin, also known Adriamycin, effectively treats a wide range of cancers, including breast cancer and pediatric leukemia. But for about 8 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 corresponding author Paul Burridge, PhD, assistant professor of Pharmacology and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
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 stem cells that can become many different types of cells, called induced pluripotent stem 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.”
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