Anthracyclines are a group of drugs that are used to combat various types of cancer and are especially effective in treating cancers such as leukemia, lymphomas, breast cancer, stomach cancer or ovarian cancer, among others. The problem is that a third of patients who receive treatment with anthracyclines develop some type of cardiac toxicity and in more than 5% of people who survive cancer, cardiac damage is irreversible.
A new study carried out by the team of the Translational Laboratory for Cardiovascular Imaging and Therapy of the National Center for Cardiovascular Research (CNIC), headed by Dr. Borja Ibáñez, who is also an interventional cardiologist at the Fundación Jiménez Díaz University Hospital, has analyzed how these drugs can damage the hearts of cancer patients and has also identified potential therapies to mitigate this serious complication.
In Europe, more than four million people are diagnosed with cancer each year. The life expectancy of these patients has improved significantly due to advances in treatments and diagnoses. For decades, anthracyclines have been part of the first line of defense in cancer treatment, combined with other drugs, and each year around three million patients in Europe are treated with these drugs.
However, despite their effectiveness, they have been noted to cause cardiac toxicity, with approximately one third of patients experiencing some form of this toxicity. In more than 5% of cases, this results in chronic heart failure, a condition that significantly reduces the patient’s quality of life.
Prevent early cardiac atrophy in cancer patients
Although cardiac toxicity from anthracyclines has been known for some time, treatments to protect the heart during their use have not been fully developed, in part because the molecular mechanisms involved are not well understood. Dr. Ibáñez and his team have delved into how cardiac anthracycline toxicity affects the metabolism of the heart, focusing their attention on the mitochondria.
“The heart is an organ that contracts incessantly throughout life. For this incredible activity, it needs a continuous supply of energy, being the organ with the highest energy needs in the entire body. Any failure in the energy production chain in the heart has very important consequences,” says Dr. Ibáñez, who is also group leader at the Networked Biomedical Research Center for Cardiovascular Diseases (CIBERCV).
“Mitochondria – he continues – are the energy centers within the cells, and their mission is to constantly produce energy through the consumption of fuel, which reaches the cell mainly in the form of fatty acids and glucose. In this work we have seen that anthracyclines significantly alter the metabolism of the heart, causing an alteration in the transport of these fuels and an irreversible dysfunction of energy production by the mitochondria.”
“We have been able to identify the molecular alterations responsible for this cardiac metabolic deterioration. “This allows us to determine processes that could be prevented with very early interventions.”
“We have observed that metabolic alterations in the heart appear very early after starting treatment with anthracyclines, long before the heart loses contractile force,” explains Anabel Díaz-Guerra, the first author of the work, who is carrying out her thesis. doctoral degree at the CNIC thanks to a scholarship from the Spanish Association Against Cancer. In fact, she adds, “we have seen that, as a consequence of these metabolic alterations, the heart begins to atrophy (its cells lose volume) as one of the first manifestations of irreversible damage.”
The findings have been published in JACC: CardioOncology and are especially important, since they appear long before the cardiac alteration can be detected with the commonly used techniques, highlights Dr. Laura Cádiz, member of the CNIC research team. “Thanks to a very thorough study at different moments of the process, we have been able to identify the molecular alterations responsible for this cardiac metabolic deterioration. This allows us to determine processes that could be prevented with very early interventions.”
According to the researchers, one of the possible interventions is related to a specific nutritional contribution that can prevent early cardiac atrophy caused by this chemotherapy drug. Researchers are testing the beneficial effect of a high-protein diet to prevent this muscle atrophy (including cardiac muscle) associated with anthracycline toxicity.
In fact, Dr. Ibáñez was awarded the Occident Foundation’s clinical research award for the study of nutritional approaches to prevent cardiotoxicity from cancer treatments. The study now published is, in part, a result of this line of research. “Within our translational vision of research, our ultimate goal is to test new therapeutic targets in patients at risk of developing cardiotoxicity due to anthracyclines. We are currently advancing a nutritional intervention study in the same experimental model, and if the positive preliminary data are confirmed, it will be the seed of a future clinical trial,” he concludes.
