{"entity":{"id":"circadian-control","kind":"pathway","name":"Circadian control","aka":[],"tldr":"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.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Chronotherapy_(treatment_scheduling)","links":[{"label":"Qian et al., Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma (Lancet Oncology 2021)","url":"https://doi.org/10.1016/S1470-2045(21)00546-5"}],"tags":["mechanism"],"related":[],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor","cytotoxic-chemotherapy"],"targets":["wee1"],"drugs":[],"companies":[],"institutions":["mskcc","penn-abramson"],"pathways":["p53-cell-cycle","myc","pd1-checkpoint"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-qian-lancet-oncol"],"journals":[],"dependsOn":[],"notes":["Leading programmes: Lévi (Warwick/Paris) on chronotherapy; Sassone-Corsi legacy (UC Irvine); Scheiermann (Geneva) on immune rhythms; MEMOIR trial (Winship/Emory)."],"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.","nodes":[{"id":"clock","label":"CLOCK/BMAL1","x":25,"y":35},{"id":"per","label":"PER/CRY (repress)","x":25,"y":70},{"id":"cycle","label":"Cell-cycle gating (WEE1, MYC)","x":60,"y":20,"targetId":"wee1"},{"id":"repair","label":"DNA repair timing","x":60,"y":50},{"id":"immune","label":"T-cell trafficking rhythm","x":60,"y":80},{"id":"tx","label":"Time-of-day drug response","x":90,"y":50}],"edges":[{"from":"clock","to":"per","type":"activates"},{"from":"per","to":"clock","type":"inhibits"},{"from":"clock","to":"cycle","type":"activates"},{"from":"clock","to":"repair","type":"activates"},{"from":"clock","to":"immune","type":"activates"},{"from":"cycle","to":"tx","type":"activates"},{"from":"repair","to":"tx","type":"activates"},{"from":"immune","to":"tx","type":"activates"}],"interventions":["Morning versus afternoon immunotherapy dosing (prospective trials ongoing)","Chronomodulated chemotherapy infusion","Clock-modulating compounds (preclinical)"]},"route":"/pathways/circadian-control/","neighbours":{"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"sleep-circadian-interventions","kind":"technology","name":"Sleep and circadian interventions in cancer","route":"/technologies/sleep-circadian-interventions/"},{"id":"time-restricted-eating","kind":"technology","name":"Time-restricted eating in cancer prevention and survivorship","route":"/technologies/time-restricted-eating/"}],"target":[{"id":"myc-gene","kind":"target","name":"MYC","route":"/targets/myc-gene/"},{"id":"wee1","kind":"target","name":"WEE1","route":"/targets/wee1/"}],"institution":[{"id":"penn-abramson","kind":"institution","name":"Abramson Cancer Center, University of Pennsylvania","route":"/institutions/penn-abramson/"},{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"pathway":[{"id":"myc","kind":"pathway","name":"MYC","route":"/pathways/myc/"},{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"}],"paper":[{"id":"paper-qian-lancet-oncol","kind":"paper","name":"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","route":"/key-papers/paper-qian-lancet-oncol/"}],"idea":[{"id":"idea-chronotherapy-immunotherapy","kind":"idea","name":"Give immunotherapy in the morning","route":"/ideas/idea-chronotherapy-immunotherapy/"},{"id":"idea-nl-sleep-circadian-survivorship-rct","kind":"idea","name":"Treat insomnia in survivors and measure whether the cancer notices","route":"/ideas/idea-nl-sleep-circadian-survivorship-rct/"}]}}