It's a double-edged sword. The chemotherapy drug doxorubicin, which is used for the treatment of many types of cancers, also causes severe, lasting heart damage in about eight percent of patients. But it's not possible to predict who among a group of patients is likely to experience this potentially deadly side effect.
Now researchers at Stanford, led by former Stanford Cardiovascular Institute instructor Paul Burridge, PhD, and cardiologist Joseph Wu, MD, PhD, have found a way to generate human heart muscle cells for study from patients' skin samples. And, as Burridge, who is is now an assistant professor of pharmacology at Northwestern University, explained in our release:
We found that cells from the patients who had experienced doxorubicin toxicity responded more negatively to the presence of the drug. They beat more irregularly in response to increased levels of doxorubicin, and we saw a significant increase in cell death after 72 hours of exposure to the drug when we compared those cells to cells from healthy controls or patients who didn’t have heart damage.
Having human cells to study is invaluable, but it's invasive to get samples of heart tissue from living patients, and the cells are difficult to keep alive long in the lab. The use of induced pluripotent stem cells, or iPS cells, to generate patient-specific heart muscle cells is a great advance. Wu, who is director of the Stanford Cardiovascular Institute explained:
In the past, we’ve tried to model this doxorubicin toxicity in mice by exposing them to the drug and then removing the heart for study. Now we can continue our studies in human cells with iPS-derived heart muscle cells from real patients. One day we may even be able to predict who is likely to get into trouble.
The study appears today in Nature Medicine.
Previously: “Chemobrain” studied by researchers at Stanford, MD Anderson, A cheaper, faster way to find genetic defects in heart patients and Stem cell study explains how mutation common in Asians affects heart health