A small minority of patients treated with a common chemotherapy drug develop severe heart damage, but there is currently no way of identifying in advance who they might be. Now, researchers have developed a method using reprogrammed stem cells derived from the patient’s own skin cells that predicts whether they fall into this group.
The chemotherapy drug doxorubicin (brand name Adriamycin) is very effective against a wide range of cancers – including breast cancer and childhood leukemia. But in around 8% of patients, it causes cardiotoxicity, where the heart muscles become damaged, and in severe cases, leads to heart failure.
Writing in the journal Nature Medicine, researchers from Stanford University, Stanford, CA, and Northwestern University, Chicago, IL, explain how they developed the stem cell technique and then went on to discover the likely genetic reasons for the differences in reaction to the drug.
In theory, it should be possible to take some of the patient’s heart cells, grow them in the lab and then test the drug on them. But, in practice, it is very difficult to isolate heart cells from patients and grow them in the lab.
Therefore, the team decided to try another route. Other studies have already reported successfully using readily available skin cells from the patient to make stem cells and then coax them into becoming the desired cell type.
For their study, the researchers took skin cells from breast cancer patients who had been treated with doxorubicin – including some with cardiotoxicity.
They reprogrammed the skin cells so they regressed to a precursor state called induced pluripotent stem cells – stem cells with the potential to differentiate into many different cell types.
The researchers then coaxed the stem cells to become heart muscle cells, treated them with doxorubicin and measured their reactions.
Lead author Paul Burridge, assistant professor of pharmacology at Northwestern, explains what they found:
“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.”
Finally, after identifying genetic differences behind the drug responses, the researchers suggest the toxic side effect might be the result of mitochondrial dysfunction. Mitochondria are tiny compartments inside cells that produce the chemical energy they need to function.
The study has obvious implications for the treatment of cancer patients. It could lead to a DNA test that finds out if a patient is likely to develop cardiotoxicity if treated with doxorubicin, Prof. Burridge suggests, and adds:
“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.”
Meanwhile, Medical News Today recently learned how researchers have succeeded in making retinal ganglion cells from stem cells derived from patients’ skins cells in a bid toward personalized treatments for glaucoma.