A new study published in Nature Cardiovascular Research may explain the mechanism behind previous research linking doxorubicin, a widely used chemotherapeutic drug, to severe cardiac damage. The study found the drug appears to trigger an immune response leading to heart stiffening and impaired function.
By uncovering the immune system’s role in this process, researchers hope to advance improved treatment strategies with fewer side effects, making cancer treatment safer for patients.
Study Details
Doxorubicin, used to treat various cancers, including breast and lymphoma, is known for its powerful cancer-fighting abilities. Researchers in the Netherlands describe it as “among the most used and useful chemotherapeutics” in a study published in The FEBS Journal. Cancer Research UK states that doxorubicin halts cancer cell growth by blocking topoisomerase, an enzyme essential for cell division.
A 2024 study in Nature found that up to 9 percent of patients taking doxorubicin experience cardiotoxicity, which can lead to heart failure. In a large study published in the American Journal of Cardiology of 22,815 patients treated with doxorubicin, 18 percent developed heart damage, and 6 percent went on to develop heart failure. However, the exact reasons behind the cardiac damage remained unclear.
Researchers from Tufts University School of Medicine and Tufts Graduate School of Biomedical Sciences aimed to investigate the immune system’s role in doxorubicin-induced heart damage.
The study found that doxorubicin can damage the heart by creating harmful molecules called reactive oxygen species (ROS). These molecules trigger inflammation, involving immune cells such as CD4+ and CD8+ T cells. Normally, these cells defend the body against infections and tumors. However, researchers discovered that doxorubicin can cause these defenders to attack the heart.
Experiments on mice showed that doxorubicin treatment increased CD8+ T cells in the heart. CD8+ T cells produce inflammatory substances that cause heart tissue damage and scarring, decreasing the heart’s ability to pump blood effectively. When the researchers removed the CD8+ T cells from the mice, the heart damage and scarring were significantly reduced.
This immune response was not limited to mice. The study also included observations from dogs and humans. Both groups showed increased levels of CD8+ T cells after receiving doxorubicin, linking the drug to immune-triggered heart damage across different species.
“Our study is the first to show that a specific cell type can cause chronic inflammation in the heart after doxorubicin treatment and the first time T-cells have been implicated in this disease,” study author Abe Bayer, a student in the Tufts graduate immunology program, said in a statement.
The researchers admit that they don’t know why the drug causes T-cells to attack the heart, but they plan to study it in the future.
“This work aims to prevent people from dying, whether from heart disease or cancer, and that means ensuring that people can take these powerful chemotherapy drugs safely,” senior author Pilar Alcaide said in the statement. “While we don’t know what the solutions will look like, this study opens many doors to potential prevention strategies that protect the heart while permitting this drug to be effective for cancer cells.”
Chemotherapy Linked to Accelerated Aging of the Heart
Recent research finds doxorubicin may make the heart age faster. This phenomenon, detailed in a review published in npj Aging, suggests that the hearts of patients treated with doxorubicin resemble those of much older individuals.
The review indicates that both naturally aged hearts and those affected by doxorubicin struggle with pumping blood efficiently. This condition, known as diastolic dysfunction, occurs when the heart doesn’t fill with blood properly between beats.
Diastolic dysfunction can cause serious issues, including atrial fibrillation (AF), a condition when the heart beats irregularly and rapidly. Research shows that AF increases the risk of stroke fivefold. A study in Frontiers in Pharmacology found that doxorubicin increases the risk of AF by 6.6 percent.
The npj Aging review also showed significant structural changes in aged hearts and those affected by doxorubicin. These changes include heart hypertrophy, a condition in which the heart muscle thickens and causes an accumulation of waste products in heart cells, hindering proper function.
Additionally, both groups exhibit increased fibrosis—a type of scarring in heart tissue. This scarring is more pronounced in those treated with doxorubicin, indicating more rapid heart aging.
Weighing the Risks and Benefits
Dr. Nathan Goodyear, an integrative cancer specialist at the Williams Cancer Institute, told The Epoch Times that while chemotherapy effectively fights cancer, it can also weaken the immune system, which plays a crucial role in overall health. This weakened immune system may not repair body tissues normally, leading to serious heart conditions such as cardiomyopathy. According to Goodyear, such damage is often permanent, underscoring the challenge in cancer treatment of weighing its benefits against potential lasting harm to patients’ health.
As the number of cancer survivors increases, it’s crucial to ensure treatments don’t cause lingering side effects, particularly to the heart, according to Dr. Nicolas Palaskas, a cardiologist at MD Anderson Cancer Center.
“Heart problems are the leading cause of death in Americans each year. Cancer is No. 2. So if we’re able to cure someone’s cancer, we certainly don’t want to leave them with any cardiovascular issues,” he wrote on the MD Anderson website.
Heart damage from cancer treatment is relatively uncommon, Palaskas said.
“Keep in mind that heart damage stemming from cancer treatment is still pretty rare. In fact, only about 5% of my cardiology patients have heart problems related to cancer treatment.” Specifically, about 2 percent of breast cancer patients and up to 5 percent of lymphoma and sarcoma patients experience heart-related side effects from doxorubicin.
Goodyear emphasized the critical need for individualized screening before starting doxorubicin treatment. He noted the importance of an echocardiogram and thorough cardiac evaluations, especially in the context of potential myocardial injury linked to COVID-19 vaccinations. Goodyear also stressed monitoring the total lifetime exposure to doxorubicin, noting that the U.S. Food and Drug Administration advises keeping the cumulative dose within 450–50 mg/m2 of body surface area to minimize risks.
Patients should watch for symptoms of heart failure or blockages, including chest pain, shortness of breath, leg swelling, and the need to sleep at an angle. Immediate medical attention can lead to timely interventions.
To minimize heart damage risk, Palaskas recommends:
- Stay active: Engage in 150 minutes of moderate or 75 minutes of vigorous physical activity weekly.
- Maintain a healthy weight: Losing 5 to 10 percent of body weight if overweight offers substantial health benefits.
- Follow a healthy diet: Adopt a Mediterranean-style or mostly plant-based diet limited in sugar.
By following these guidelines, patients can protect their heart health and improve overall outcomes during and after cancer treatment.