# Circadian control

Source: https://onco.cc/pathways/circadian-control/  
OnCo record `circadian-control` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Pathway
- Last checked: 2026-09-08
- Tags: mechanism
- Analogy: 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.
- Interventions: Morning versus afternoon immunotherapy dosing (prospective trials ongoing); Chronomodulated chemotherapy infusion; Clock-modulating compounds (preclinical)

## Notes

- Leading programmes: Lévi (Warwick/Paris) on chronotherapy; Sassone-Corsi legacy (UC Irvine); Scheiermann (Geneva) on immune rhythms; MEMOIR trial (Winship/Emory).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Chronotherapy_(treatment_scheduling)
- Qian et al., Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma (Lancet Oncology 2021): https://doi.org/10.1016/S1470-2045(21)00546-5

## Connected records

- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Sleep and circadian interventions in cancer](https://onco.cc/technologies/sleep-circadian-interventions/), [Time-restricted eating in cancer prevention and survivorship](https://onco.cc/technologies/time-restricted-eating/)
- targets: [MYC](https://onco.cc/targets/myc-gene/), [WEE1](https://onco.cc/targets/wee1/)
- institutions: [Abramson Cancer Center, University of Pennsylvania](https://onco.cc/institutions/penn-abramson/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- pathways: [MYC](https://onco.cc/pathways/myc/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/)
- key papers: [Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma in the USA (MEMOIR): a propensity score-matched analysis of a single-centre, longitudinal study](https://onco.cc/key-papers/paper-qian-lancet-oncol/)
- ideas: [Give immunotherapy in the morning](https://onco.cc/ideas/idea-chronotherapy-immunotherapy/), [Treat insomnia in survivors and measure whether the cancer notices](https://onco.cc/ideas/idea-nl-sleep-circadian-survivorship-rct/)

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