Cancer drugs and abnormal heart rhythms

Professor Derek Steele is researching ways to prevent the abnormal heart rhythms that can be caused by some cancer drugs.

Professor Derek Steele

Heart failure is not the only way in which chemotherapy could affect your heart. Scientists are always searching for more effective drugs to fight cancer. One new class of drugs, called EPAC inhibitors, are being investigated for use against certain cancers, as well as diabetes, heart failure, obesity and chronic pain. But Professor Derek Steele and his team at the University of Leeds have discovered that they can also cause serious abnormal heart rhythms, based on tests on heart cells in a petri dish and in rats.

Understanding the link

Professor Steele, who is an expert in the processes that underpin the beating of the heart, says: “While ongoing research suggests these drugs may be effective in treating a range of conditions, toxic side effects on the heart could limit their future clinical use. We raised this potential pitfall in a recently published research paper, which describes disruption of the normal heart rhythm by EPAC inhibitor drugs. However, these drugs might still be useful if we can block the harmful effects on the heart.”

This could lead to new ways to prevent the harmful effects of diabetes on your heart and also allow new drugs to be used more safely

Normally, the EPAC pathway in the heart helps defend the body against harmful free radicals, which can be produced during exercise and stress. EPAC inhibitors halt this defence, which means heart cells can be damaged by the free radicals. This can result in an abnormal heart rhythm.

Professor Steele is working to learn more about the EPAC pathway, and why these new cancer drugs and diabetes affect it. This could lead to new ways to prevent the harmful effects of diabetes on your heart and also allow new drugs to be used more safely, and potentially at higher concentrations.

Identifying new approaches

His team found that an existing drug for angina, called ranolazine, can prevent the irregular heart rhythms caused by these drugs. Tests have only been carried out on single heart cells in the lab, so more research is needed.

The idea that you should take a drug and just suffer the side effects on your heart is not acceptable

“Ranolazine is promising because it is licensed for the treatment of angina, so it has been tested in clinical trials,” says Professor Steele. “It has been available for a number of years, and we know it doesn’t generally cause side effects. With chemotherapy, some of the most effective drugs in use have the potential to damage the heart, so we could give one drug to switch off a tumour and give another drug to prevent serious side effects on the heart.”

The BHF has given Professor Steele and his team £809,000 over five years to research this issue. Their study is in its first year, but the results are promising.

“The idea that you should take a drug and just suffer the side effects on your heart is not acceptable,” says Professor Steele. “We believe our work identifies a new approach to prevent the toxic effects of these drugs on heart rhythm.”

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