SPOKANE, Wash. - Treatment for breast cancer commonly includes radiation therapy, which offers good chances of success but comes with a serious long-term side effect: toxicity due to radiation that reaches the heart, causing DNA damage in healthy heart cells. Over time, this can lead to heart disease and eventually heart failure.
A new study conducted by researchers in the Washington State University College of Pharmacy and Pharmaceutical Sciences suggests that a preventive solution may lie in the biological clock, the built-in time-keeping mechanism that keeps us on a 24-hour cycle of rest and activity and regulates a wide variety of processes in our bodies.
Published in the FASEB Journal, their study used a rodent model to determine whether the biological clock is involved in heart toxicity from radiation therapy and could be used as part of a strategy to reduce this toxicity. Their findings showed that after receiving a dose of radiation to the heart, mice with disrupted biological clocks had significantly worse heart function than control mice.
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In addition, the researchers demonstrated that a protein known as Bmal1--which drives 24-hour rhythms in the expression of many genes--plays an important role in protecting the heart from radiation-related damage.
"Our findings suggest that Bmal1 serves as a biomarker for the susceptibility to radiation-induced DNA damage to the heart," said Shobhan Gaddameedhi, an assistant professor in the Department of Pharmaceutical Sciences and the study's senior author.
Though more research is needed, the researchers are hopeful that their discovery could someday be used to improve treatment outcomes for breast cancer patients. Panshak Dakup--the study's first author and a PhD in pharmaceutical sciences student--said their finding holds promise for personalized medicine. "For example, in breast cancer patients who have a long history of working night shifts, the expression of biological clock proteins such as Bmal1 may be compromised, and it could be that radiation therapy is not the best option for them."
Gaddameedhi added that it could also be used to optimize the timing of radiation therapy so it is provided when a patient's Bmal1 level offers the greatest level of protection from heart damage. That timing may vary depending on a person's chronotype--whether they are early birds or night owls--as well as on other factors that influence the status of the master biological clock, such as shiftwork or frequent travel across time zones.