Novel Method to Foresee Chemo-induced Heart Failure

A small number of patients treated with a common chemotherapy medicine, doxorubicin, develop serious heart damage, but there is presently no method of determining in advance who they might be. Now, scientists have come up with a technique using reprogrammed stem cells produced from the patient’s own skin cells that forecasts whether they fall into this category.

The chemotherapy medicine doxorubicin (brand name Adriamycin) is extremely effective towards a number of cancers – such as breast cancer and childhood leukemia, but in about 8 percent of patients who are administered this chemotherapy, it leads to cardiotoxicity, where the heart muscles become damaged, and in serious cases, results in heart failure.

Presenting their research in the journal Nature Medicine, investigators from Stanford University and Northwestern University describe how they designed the stem cell method and then went on to find out the likely genetic factors for the variations in reaction to the drug.

Theoretically, it must be possible to take some of the patients heart cells, develop them in the lab and then analyze the drug on them. But, in practice, it is really challenging to isolate heart cells from patients and develop them in the lab.

For that reason, the team made the decision to try out another way. Other research have previously reported successfully using easily accessible skin cells from the patient to make stem cells and then coax them into becoming the required cell type.

For their research, the investigators obtained skin cells from breast cancer sufferers who had been treated with doxorubicin – which includes some with cardiotoxicity.

They re-programmed the skin cells so they regressed to a precursor state known as induced pluripotent stem cells – stem cells with the possibilities to distinguish into a variety of cell types.

The investigators then coaxed the stem cells to turn into heart muscle cells, treated them with doxorubicin and assessed their reactions.

Outcomes could guide to a DNA test for possibility of cardiotoxicity

Lead author Paul Burridge, says:

“Our outcomes revealed that heart cells from sufferers who have cardiotoxicity were considerably more sensitive to doxorubicin-caused toxicity. They had more structural damage, decreased contraction, DNA damage and died more quickly.”

Lastly, after determining genetic variations behind the drug reactions, the investigators recommend the toxic side effect may be the outcome of mitochondrial dysfunction. Mitochondria are small compartments within cells that generate the chemical energy they require to function.

The research has obvious implications for the therapy of cancer patients. It could guide to a DNA test that discovers if a individual is probably to develop cardiotoxicity if handled with doxorubicin, Prof. Burridge suggests, and adds:

“This sufferer could then be given an substitute chemotherapy or a reduced dose. In contrast, in sufferers who are tolerant to doxorubicin-stimulated cardiotoxicity it might be possible to increase the dose and have a superior chance of success with their chemotherapy.”

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