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A team of researchers from Andalusian Center for Molecular Biology and Regenerative Medicine (Cabimer) and the University of Seville (US), in collaboration with the Virgen Macarena University Hospitalhave identified a “fundamental” mechanism that links the 24-hour circadian cycle with the “precise” repair of DNA breaks. This finding, centered on the circadian protein Cryptochrome1 (CRY1), suggests that the time of day that radiotherapy is administered can “significantly influence the effectiveness of treatment for certain types of cancer.”
Thus, breast cancer patients with tumors that express higher levels of CRY1 were more sensitive to radiotherapy. Furthermore, a retrospective analysis with data from patients at the Virgen Macarena University Hospital revealed a significant difference in overall survival based on time of irradiation. Irradiation in the afternoon/night, when CRY1 levels naturally increase, made the tumor samples more sensitive to radiotherapy and improved the patient’s prognosis, US explained in a note.
This effect was observed, for example, in patients with prostate cancer and breast cancer, but not in lung cancer or gliomas. Therefore, these findings open the door to exploring the therapeutic potential of irradiation at specific times of the day, a phenomenon known as chronoradiotherapy. Maintaining genomic stability is essential to prevent the appearance of cancer. Therefore, it is essential that DNA breaks are repaired as precisely as possible.
Consequently, it is relatively common for cancer cells to be unable to repair their DNA efficiently. On the other hand, multiple oncological treatments, such as radiotherapy, exploit this weakness by generating breaks in the DNA that the tumor cells will be unable to repair. This study shows that DNA break repair in human cells exhibits a circadian oscillation. That is, its efficiency is not homogeneous, but varies cyclically depending on the time of day. In a normal cycle in humans, repair activity peaks in the early morning and then progressively declines until evening. This efficiency then increases again during the night.
The research identifies that this regulation depends on a central component of the biological clock: the CRY1 protein. This protein naturally acts as a timer and its abundance changes naturally during the day/night cycle. In fact, the repair process reacts directly to CRY1 levels. When CRY1 levels are low (corresponding to early morning in humans), efficient DNA repair is stimulated.
On the contrary, when CRY1 levels increase (which naturally occurs in the afternoon/evening), repair is reduced, increasing the sensitivity of cells to DNA-breaking agents such as ionizing radiation. This circadian regulation has a direct impact on cancer progression and in the response to radiotherapy in specific tumors. The study results suggest that the reduction in repair that occurs when CRY1 levels are high can be exploited therapeutically.
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