For a patient, choose the time of their sessions
radiotherapy looks like a practical puzzle: schedule, fatigue, availability of a loved one. It has long been thought that morning or late afternoon makes no difference to the medical result. But recent work shows that the body does not react in the same way at all times of the day.
The question of time of day takes on importance, because the radiotherapy is based on breaks in DNA that cancer cells repair poorly. A team from the CABIMER center and the University of Seville has shown a link between our internal clock and this repair via a key protein, CRY1. Choosing the right time slot could make the rays more toxic to the tumor and gentler to healthy tissue. And this niche is not necessarily what we imagine.
DNA repair rate varies throughout the day
Our body must maintain genomic stability to prevent the appearance of cancer. Basically, DNA breaks must be correctly and precisely repaired so that they do not degenerate into cancer. But cancer cells are often unable to repair their DNA effectively. It is this weakness that anticancer treatments exploit by generating breaks in the DNA that these cancer cells cannot repair, which leads to their death.
What we have suspected for several years is that the repair of DNA breaks by our body is not homogeneous all day long. Its effectiveness varies over time and this circadian oscillation could be exploited to treat cancer.
Circadian clock, CRY1 and DNA repair under radiotherapy
Our body follows a 24-hour cycle, regulated bycircadian clock which synchronizes sleep, temperature, hormones. At the heart of this system, the CRY1 protein plays the role of a molecular timer, its quantity rising and falling over the hours. The researchers observed that repair of DNA breaks peaks in the late night and early morning, then declines until the evening before increasing again during the night.
When the CRY1 level is low, in the early morning, the cells initiate a fine and efficient repair, with a long restoration of the DNA. In the late afternoon and evening, when CRY1 reaches a peak, this repair becomes less efficient and the cells are more sensitive to ionizing rays or drugs that break DNA. In cell culture, survival drops precisely when CRY1 is at its highest.
When the time of day modifies the effect of radiotherapy
By analyzing thousands of tumors from the program The Cancer Genome Atlasresearchers observed that breast cancers with high levels of CRY1 responded better to radiotherapy. In this cohort, patients with high CRY1 expression had a prolonged median survival of approximately 1.5 years after radiotherapy compared to those whose tumors expressed little (an even more pronounced effect when we also take into account another CCAR2 protein with more than 2.5 years of median gain).
A retrospective study carried out at the Virgen Macarena Hospital in Seville provides a concrete signal: in patients treated for breast or prostate cancer, irradiation scheduled for the afternoon or evening, a period when CRY1 is naturally more abundant, was accompanied by better overall survival than sessions in the morning. This effect has not been found for lung cancers or certain gliomas, which suggests that the impact of the time of day also depends on the type of tumor.
Chronoradiotherapy: for patients?
Other trials on head and neck, cervical, or breast cancers show that schedule influences side effects. Tomorrow, chronoradiotherapy could therefore consist of setting the treatment slots on the clock specific to each patient and each tumor.
This new study confirms the importance of the time of treatment administration depending on the patient and the tumor. Previous results had highlighted this importance for chemotherapy or immunotherapy. Today, many questions remain unanswered but the stakes are high since it is a question of reducing the side effects and the effectiveness of anticancer treatments.