Researchers at Charité-University of Medicine in Berlin have developed an approach to determine the best time to treat cancer based on specific types of breast cancer cells. The researchers employed multiple computational tools to uncover the cellular and genetic factors that shape drug sensitivity at a given time of day. The researchers hope to leverage circadian rhythms to improve anticancer drug treatments.
When do our bodies start working?
How effective medications are depends on a number of factors, including the time of day they are taken. Why? Because our bodies don’t work the same way all the time, but rather follow a cycle that is set by the body’s internal clock, known as the circadian rhythm. But because circadian rhythms vary from person to person and depend on a variety of factors, it’s difficult to adjust medication schedules to a patient’s body clock.
The body’s internal clock regulates many different metabolic functions and processes, such as sleep and digestion. But organs aren’t the only ones that are more or less active depending on the time of day. Even individual cells follow a cycle determined by the body’s rhythm, making their response to external influences vary depending on the time of day. This is particularly important in chemotherapy for cancer treatment. Previous studies have shown that chemotherapy is most effective when cancer cells are dividing. But this discovery has not been widely used in treating patients until now.
A multidisciplinary team led by Dr. Adrián Enrique Granada of the Charité Comprehensive Cancer Center sought to fill this gap. The team set out to find the best time to administer the drug based on the tumors’ circadian rhythm. They published their results in Nature Communications on August 22.
Triple negative breast cancer as an example
“We cultured cells from triple-negative breast cancer patients to monitor how they responded to drugs at different times of the day,” says Caroline Ector, a research associate in Dr Adrian Granada’s research group. Triple-negative breast cancer is a very aggressive type of breast cancer, and there are few effective treatments available for it. “We used live imaging, a method of continuously monitoring living cells, and sophisticated data analysis techniques to monitor and assess the circadian rhythms, growth cycles and drug responses of these cancer cells in detail.”
In this way, the researchers identified specific times of day when cancer cells are most responsive to drug treatments. For example, the chemotherapy drug 5-fluorouracil (5-FU) was found to be most effective against a certain type of cancer cell between 8 a.m. and 10 a.m. The study also showed that the crucial aspects here are certain cellular and genetic factors. The scientists were able to identify genes that are key to the circadian effects of certain drugs. “We call them master clock genes,” explains Dr. Granada. “They have a major impact on how cancer cells respond to treatments given at different times of the day.”
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This approach could be used to create detailed profiles showing how different types of cancer cells respond to different drugs at different times. “This could help identify the most effective drug combinations,” says Dr. Granada, according to EurekAlert. “Overall, our results suggest that personalized treatment plans based on individual biological rhythms could significantly improve the effectiveness of cancer treatment,” he adds. What’s more, unwanted side effects could also be reduced.
For these results to contribute to clinical practice soon, the results need to be verified in studies involving larger groups of patients. “We also plan to study the molecular mechanisms behind the biological effects on drug sensitivity, in order to improve treatment times and identify new therapeutic targets,” says Granada.