Circadian control
Cells run on a 24-hour clock that gates cell division, DNA repair, and drug metabolism. Cancers often break their clocks, and the time of day a drug or immunotherapy is given can change how well it works.
The CLOCK/BMAL1–PER/CRY loop times metabolism, cell-cycle checkpoints, and DNA repair; shift work is a probable carcinogen (IARC 2A) and clock-gene disruption accelerates tumorigenesis in mice. Chronomodulated chemotherapy (Lévi, oxaliplatin/5-FU) improved tolerability in colorectal cancer; retrospective and prospective data (MEMOIR, 2024-25) suggest checkpoint inhibitors given earlier in the day yield longer survival, likely through T-cell trafficking rhythms. Clock-targeting drugs (REV-ERB agonists, CRY stabilisers) are preclinical. Implementation is cheap but trial evidence is still limited.
In one picture
A city that lowers its bridges only at certain hours. Send the army (drug, T cells) when the bridges are down and it gets in; send it at midnight and it waits outside.
Diagram
top- Morning versus afternoon immunotherapy dosing (prospective trials ongoing)
- Chronomodulated chemotherapy infusion
- Clock-modulating compounds (preclinical)
Notes
top- Leading programmes: Lévi (Warwick/Paris) on chronotherapy; Sassone-Corsi legacy (UC Irvine); Scheiermann (Geneva) on immune rhythms; MEMOIR trial (Winship/Emory).