Cancer and heart failure
Many vital drugs used to treat cancer are ‘cardiotoxic’ – they can cause heart failure – so they have to be used at low doses. But BHF-funded research could change this.
“Because chemotherapy agents can have cardiotoxic effects the clinical doses currently used are kept quite low. This means they are not as effective as they could be against cancer,” explains Dr David Grieve.
Research in Dr Grieve’s lab at Queen’s University Belfast investigates why some cancer drugs have cardiotoxic effects and how this can be prevented.
Chemotherapy drug Doxorubicin
Dr Grieve’s work focuses on a drug called Doxorubicin, used to treat a variety of cancers including breast, ovarian and bladder. “Virtually all chemotherapy drugs have some kind of cardiotoxic action but we focused on Doxorubicin because it’s one of the most widely used,” says Dr Grieve
We focused on Doxorubicin because it’s one of the most widely used chemotherapy drugs
Dr David Grieve
Dr Grieve and his team found out how an enzyme called NADPH oxidase can cause heart failure due to chemotherapy.
Healthy people normally have low levels of NADPH oxidase in their cells.
The body’s response to the chemotherapy can cause levels of it to increase. The researchers believe this may damage the heart. The researchers mimicked the sort of treatment given to cancer patients by giving mice Doxorubicin.
They then looked at the effects of switching off NADPH oxidase, and found that Doxorubicin treatment no longer led to heart damage. This remained the case even after several rounds of treatment with the drug.
Their next aim is to understand the precise role of NADPH oxidase in causing human heart failure. This knowledge could help us find a practical way to prevent cardiotoxicity during chemotherapy.
Dr Grieve adds, “If we can discover a co-therapy to prevent the cardiotoxic effects it would mean that the cancer treatment could be given at a much higher dose thereby saving lots of lives.”
As well as producing a drug to block NADPH oxidase in cancer patients, Dr Grieve hopes that their work could one day lead to a simple blood test to assess a person’s NADPH oxidase activity levels. If cancer patients are found to have high levels of NADPH oxidase, they might be at greater risk of heart failure while on some treatments. Doctors could then adjust their medication accordingly, potentially saving lives.
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