IU researchers discover new ways to prevent serious side effects in breast cancer patients

Researchers at the Indiana University School of Medicine are learning more about ways to prevent the serious side effects of chemotherapy used to treat breast cancer patients. Work conducted by the Schneider lab at the Vera Bradley Foundation Center for Breast Cancer Research at the IU Melvin and Bren Simon Comprehensive Cancer Center and led by Xi Wu, PhD, was recently published in nature communications.

Anthracyclines belong to a class of chemotherapy agents that are used to treat a variety of cancers and remain an important part of therapy for high-risk breast cancer patients. While they are effective in improving cure rates, they can also cause serious heart damage, including heart failure, which is often irreversible.

“This is of critical clinical importance for breast cancer patients, as there are no proven strategies for prevention or interventions for cardiotoxicity,” said Wu, a Vera Bradley Foundation fellow and first author of the paper. “In addition, there are no clinically indicated biomarkers to predict which patients are at risk of developing this side effect before starting an anthracycline-based treatment. In our publication, we provide molecular mechanisms by which a genetic variant previously identified by our group may lead to the Clinical development of anthracycline-induced cardiotoxicity in patients”.

Previous research from Schneider’s lab suggested that people may be more likely to experience serious heart damage, known as cardiotoxicity, after receiving anthracycline chemotherapy based on their genetics, but there hasn’t been enough information to determine which specific genes are independent of other disorders. cardiac. risk factor’s. Wu and his colleagues used stem cell-derived pluripotent cardiomyocytes, the cells responsible for contracting heart muscles, to show that an inherited gene variant decreased the cells’ ability to contract heart muscles after being exposed to radiation. doxorubicin, an anthracycline chemotherapy drug.

We know it’s difficult to balance the toxicity needed to kill cancer cells while protecting the rest of the patient’s healthy body. These findings may help us begin to understand why some patients may be at higher risk of developing this devastating side effect, but more work is needed to devise strategies to effectively prevent this from occurring. This exciting work is a big step in that direction.”

Bryan P. Schneider, MD, Vera Bradley Professor of Oncology at the IU School of Medicine, lead author

Their findings also uncovered unexpected potential value for dexamethasone, a steroid pretreatment routinely used to prevent nausea and allergic reactions. This drug, or perhaps other drugs that work in a similar way, may be a key strategy to minimize cardiotoxicity as a side effect of chemotherapy. More work is underway to further explore the optimal approach. Ultimately, the overall goal of this paper is to help clinicians understand the risk level of certain patients before they use an anthracycline-based therapy, and also to minimize the chance of heart failure for those at high risk.

Schneider is also a Physician Scientist at the IU Melvin and Bren Simon Comprehensive Cancer Center, as well as an Investigator at the Vera Bradley Foundation Center for Breast Cancer Research.

This publication was supported by the Vera Bradley Foundation for Breast Cancer, a Susan G. Komen Award, and the IU Precision Health Initiative. It was also supported in part by a Vera Bradley Postdoctoral Fellowship to Wu.


Magazine reference:

Wu, X. et al. (2022) A noncoding GWAS variant affects anthracycline-induced cardiotoxic phenotypes in iPSC-derived human cardiomyocytes. nature communications. doi.org/10.1038/s41467-022-34917-y.

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