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Cause of Heart Damage From Cancer Drugs Identified

Researchers claimed that they are one step closer to safer cancer drugs after identifying the likely reason why some of these treatments damage the heart.

Modern drugs can be very effective at treating cancer and have led to greatly improved survival rates, said the authors of a new study, published in the journal Science Advances.

However, some cancer treatments can cause cardiotoxicity, they pointed out. This can present in a variety of ways, ranging from a slight change in the heart's pumping ability to debilitating heart failure, which means that some patients are confronted with treatment-induced heart problems.

"While there have been advances in treating cancer, one of the consequences has been a risk of heart damage from these drugs," alerted British Heart Foundation (BHF) Medical Director, Professor Sir Nilesh Samani.

The ways in which these drugs cause damage, however, has remained elusive, emphasised the authors.

Proteins Associated With Heart Disease Risk

For the international data analysis study, led by University College London (UCL), researchers sourced information from up to 36,548 UK Biobank subjects who had data on both cardiac magnetic resonance images and genotyping. They searched through the DNA of the subjects without pre-existing heart disease and identified genetic variants linked to changes to the structure and function of the ventricles.

Using Mendelian randomisation, the researchers then pinpointed 33 proteins (coded for by these genetic variants) that were present in the blood and associated with the risk of developing several heart diseases, including types of heart failure and atrial fibrillation.

Through large-scale analyses of the plasma proteome, and linkage to mRNA expression, protein interactions, and drug compound databases, the authors said that they had identified a prioritised set of 33 proteins with a robust cardiac magnetic resonance and cardiac outcome fingerprint.

They also found that over half (52%) of the druggable proteins could be mapped to compounds with known oncological indications or side effects.

"Crucially, many of these proteins are the targets of drugs currently used to treat cancer," they stressed.

Future Safer Treatment Hope

The team of researchers also highlighted that their findings could explain how cancer drugs cause their damaging effects on the heart.

"Cardiotoxicities of several cancer treatments might represent 'mechanism-based adverse effects'," they postulated.

The findings provided leads to facilitate drug development for cardiac disease, suggested the authors, and could help to identify those at increased risk. In addition, the study revealed new potential drug targets for repurposing or de novo drug development for cardiac therapies.

"These may work by inhibiting proteins linked to higher disease risk, or activating proteins linked to lower risk," they said.

Asked to comment by Medscape UK News, Dr Henry Stennett, research information manager at Cancer Research UK, said: "The majority of cancer treatments available today are kinder than their predecessors of the past. But many still come with negative side effects which can include toxicity to other parts of the body, like the heart."

He emphasised the need for this study: "Research like this is absolutely vital to make sure that we continue to develop new treatments which are not only more effective, but also mean that patients aren't having to endure painful side effects on top of an already difficult cancer diagnosis."

Dr Floriaan Schmidt, UCL Institute of Cardiovascular Science, and lead author, commented: "The proteins identified in our study will help to accelerate future drug development, offering scientists a blueprint for new treatments for both cancer and heart diseases."

This could help drug developers to be more confident of the effects of the drugs that they design, he said, "whether that’s shrinking tumours without causing damage elsewhere or improving the heart's pumping action".

ProfSir Nilesh Samani added that the research pointed the way towards developing safer and more refined drugs. "One day, worries about developing heart problems after cancer treatment might be a thing of the past.".

Funding for the study was provided by the British Heart Foundation, UKRI/NIHR Multimorbidity fund Mechanism and Therapeutics Research Collaborative, the Rosetrees Trust, the National Institutes of Health (USA), the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart, and the Horizon EiC Pathfinder project DMC-next. AFS and FWA have received Servier funding for unrelated work,while SWvdL has received Roche funding for unrelated work. CG receives a salary from SkylineDx BV. The authors declare no other competing interests.