Nature sub-journal: Prevention of serious side effects of chemotherapy used to treat breast cancer patients

Researchers at Indiana University School of Medicine are learning more about ways to
prevent the serious side effects of chemotherapy used to treat breast cancer patients.
The work done by Schneider's lab at the Vera Bradley Foundation Breast Cancer Research Center at the International University Melvin and Brunsimon Comprehensive Cancer Center, led by Dr.
Xi Wu, was recently published in
Nature Communications.

Anthracyclines belong to a class of chemotherapy drugs used to treat a variety of cancers and remain an important part of the treatment of
patients with high-risk breast cancer.
While effectively improving cure rates, they can also lead to serious heart damage, including heart failure, which is often irreversible
.

"This has critical clinical implications for breast cancer patients because there are currently no proven strategies to prevent or intervene in cardiotoxicity, and furthermore, there are no clinically indicated biomarkers to predict which patients are at risk
of developing this side effect before starting anthracycline-based therapy.
" In our publication, we provide a molecular mechanism by which genetic variants previously identified by our group may lead to the clinical development
of anthracycline-induced cardiotoxicity in patients.
”

Previous research in Schneider's lab has shown that people may be more likely to experience severe heart damage, known as cardiotoxicity, after receiving anthracycline chemotherapy, depending on genes, but there is not enough information to determine which specific genes are independent of other heart risk factors
.
Wu and her colleagues used pluripotent stem cell-derived cardiomyocytes (the cells responsible for contracting the heart muscle) to show that genetic variants reduced the cells' ability to contract the heart muscle after exposure to
doxorubicin, an anthracycline chemotherapy drug.

"We know it's tricky to balance the toxicity needed to kill cancer cells while protecting the rest of the patient's healthy body," said Bryan P.
Schneider, MD, the Vera Bradley Professor of Oncology at Indiana University School of Medicine and senior author
of the publication.
"These findings can help us begin to understand why some patients may be at increased risk of developing such devastating side effects, but more work is needed to design effective strategies
to prevent this from happening.
" This exciting work is an important step
in this direction.
”

Their findings also reveal an unexpected potential value for dexamethasone, a steroid pretreatment commonly used to prevent nausea and allergic reactions
.
This drug, or other drugs that work in a similar way, may be a key strategy
for minimizing the side effects of chemotherapy with cardiotoxicity.
More work is underway to further explore the best approach
.
Ultimately, the overarching goal of this work is to help physicians understand the level of risk in some patients before using anthracycline therapy and minimize
the chance of heart failure in high-risk patients.