Investigation into the potential mechanisms underlying normal tissue response to chronomodulated radiation

Radiotherapy for cancer is an important treatment that greatly improves patients’ chance of survival and remission. However, a proportion of patients experience significant side effects because of the inevitable irradiation of healthy tissue, negatively impacting their quality of life.

Recent research has explored whether radiotherapy toxicity could be reduced by tailoring the time of treatment to the circadian cycle, however studies are difficult to compare and data is conflicting. Therefore, this research aimed to investigate the potential mechanisms underlying the response of normal tissues to radiation exposure at different stages of the circadian cycle.

In this work, Drosophila melanogaster models irradiated at different times of day yielded inconsistent trends between a variety of fly strains. As Drosophila are considered an important model for understanding circadian biology, the results presented here warrant further investigation for assessing the impact of time on radiosensitivity.

On the other hand, fibroblast models highlight that radiation timing can have a significant effect on the number of cells progressing through the cell cycle in some patients. Further evidence is also shown in regression analyses in a cohort of prostate cancer patients where SNPs in CLOCK, PER3, VAMP3 and RASD1 can predict a deterioration in both acute and late side effects.

Overall, this research has shown that the normal tissue response differs in some patients depending on the time of exposure to radiation, likely due to variations in the cell cycle over the course of the day. Furthermore, there is an association between SNPs in circadian rhythm genes and side effects in prostate cancer patients, highlighting the potential for these as predictive biomarkers. Importantly, this research has provided further evidence in support of chronomodulated radiotherapy for improving side effects and will better inform a prospective clinical trial.