Scientists are working to understand why doxorubicin, a popular chemotherapy drug used for over 50 years, sometimes causes serious heart damage.
This drug, which helps slow or stop cancer growth, can stiffen the heart and increase the risk of heart failure in some patients.
Researchers from Tufts University are investigating this issue to find ways to prevent such complications.
Doxorubicin is a go-to drug for many oncologists because it effectively stops cancer cells from dividing.
However, it can also trigger an inflammatory response in the heart, which can lead to damage.
Until now, no one has been able to clearly explain why this happens or how to prevent it. The Tufts research team is trying to fill these knowledge gaps.
Their study, published on July 17 in Nature Cardiovascular Research, found that doxorubicin causes high levels of CD8+ cytotoxic T-cells, a type of immune cell, in the blood of healthy mice.
These findings were also seen in dogs and humans with lymphoma. Further research showed that these T-cells move to the heart and interact directly with heart tissue, causing inflammation and scarring (fibrosis).
When the T-cells were removed, the inflammation and fibrosis in the heart decreased.
“This is the first time we’ve identified a specific cell type causing chronic heart inflammation after doxorubicin treatment,” says Abe Bayer, a Tufts MD/Ph.D. student and first author of the study.
“Blocking these T-cells from entering the heart might help prevent the heart damage linked to the drug.”
The research team discovered that doxorubicin makes the CD8+ T-cells mistakenly attack the heart tissue as if it were a foreign invader.
These T-cells release molecules meant to kill viruses, but in this case, they cause fibrosis, making the heart less flexible and unable to contract properly.
This study is crucial because it suggests new ways to prevent heart damage while allowing the chemotherapy drug to continue fighting cancer effectively.
Senior author Pilar Alcaide, a professor at the School of Medicine, emphasizes the importance of this work: “We aim to prevent deaths from both heart disease and cancer. This study opens many doors to potential prevention strategies that protect the heart.”
The team plans to explore how to block CD8+ T-cells from entering the heart without affecting doxorubicin’s cancer-fighting abilities.
They also aim to identify molecules that attract T-cells to the heart, which could serve as biomarkers to predict and monitor heart damage. This would allow for more personalized and safer treatment plans for patients.
The study’s success was partly due to the availability of cancer patient samples from both humans and dogs. Dogs experience similar side effects from doxorubicin, and the researchers are collaborating with veterinary experts to apply their findings to both humans and animals.
Bayer is optimistic about the impact of this research: “I hope it inspires more people to explore new ideas in established fields. Science is too complex to think we’ve figured everything out.”
This promising research could lead to safer chemotherapy treatments, protecting patients’ hearts while fighting cancer effectively.
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