A new study has identified proteins in the blood that are linked to an increased risk of heart disease and are also affected by cancer drugs.
This helps explain how cancer drugs cause damage to the heart and could help identify those at increased risk. In the long term, this could improve cancer treatments and help develop new drugs that do not affect these proteins. The study also identifies potential drug targets for treating heart diseases, such as heart failure, by inhibiting high-risk proteins or activating low-risk proteins.
A recent study has identified the underlying cause of heart damage caused by certain cancer drugs. Cardiotoxicity, or damage to the heart muscle, is a known side effect of some cancer treatments. However, until now, the exact mechanism behind this damage was not fully understood.
A genome-wide association study conducted by researchers identified genetic variants in nearly 37,000 people linked to changes in the structure and function of the heart’s pumping chambers. Using Mendelian randomization, they identified 33 proteins coded for by these genetic variants associated with the risk of developing heart diseases, including heart failure and atrial fibrillation. Many of these proteins are targeted by cancer drugs currently used in treatment.
Lead author Dr. Floriaan Schmidt (UCL Institute of Cardiovascular Science) said: “The proteins identified in our study will help accelerate future drug development, offering scientists a blueprint for new treatments for cancer and heart diseases. This can help them be more confident of the effects of the drugs they design – whether that’s shrinking tumors without causing damage elsewhere or improving the heart’s pumping action.”
Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, said: “While there have been advances in treating cancer, one of the consequences has been a risk of heart damage from these drugs. This research points the way towards developing safer and more refined drugs so that, one day, worries about developing heart problems after cancer treatment might be a thing of the past.”
Heart failure is caused by dysfunction of the right or left ventricle, and drug development for cardiac disease has a high failure rate. Cardiac magnetic resonance imaging is used to diagnose and quantify biventricular function and morphology. Researchers used a deep-learning algorithm to extract measures from both ventricles. They performed a genome-wide association study to identify genetic variants linked to ventricle changes.
They then used a framework to perform drug target analyses using human genetic data and prioritize plasma proteins for their involvement with ventricular traits and cardiac outcomes. Repurposing opportunities were identified by extracting cardiovascular indications and side effects from various databases.
This study used cardiac magnetic resonance images and protein data to identify circulating plasma proteins associated with changes in the structure and function of the heart’s pumping chambers.
The researchers used Mendelian randomization and drug target analysis to pinpoint 33 proteins that may be potential drug targets for heart failure therapies. They also investigated the mechanisms of cancer cardiotoxicity caused by certain drugs.
The study used genetic data to identify proteins in the blood associated with various heart conditions and measures of heart structure and function. The researchers found 33 such proteins, 25 directly or indirectly druggable, providing potential targets for drug development. Some of these proteins were also linked to oncological indications, suggesting that compounds targeting them may also be used to prevent cardiac events.
However, the study also noted that an imperfect understanding of the relation between heart structure and disease makes it difficult to predict how these proteins may affect specific outcomes.
The study found that specific proteins targeted by drugs regulate the heart’s structure and function. These proteins may be potential targets for new therapies to treat heart failure and minimize the risk of cardiotoxicity from cancer treatment. Understanding the molecular mechanisms involved in regulating the heart may lead to more effective treatments for heart failure and cancer cardiotoxicity.
In conclusion, the study highlights the potential of druggable proteins in regulating cardiac structure and function and their implications for heart failure therapies and cancer cardiotoxicity. Targeting these proteins can lead to new and effective treatments for heart failure and minimize the risk of cardiotoxicity associated with cancer treatment.
The study results were annotated with tissue-specific mRNA expression and protein-protein interaction data.
The study emphasizes the importance of understanding the molecular mechanisms involved in cardiac function and dysfunction to develop targeted therapies for heart-related conditions.
The study was funded by the British Heart Foundation.
Journal Reference
- Schmidt, A. F., Bourfiss, etal. Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity. Science Advances. DOI: 10.1126/sciadv.add4984