title: Circadian clock, cancer, and chemotherapy.
abstract: The circadian clock is a global regulatory system that interfaces with most other regulatory systems and pathways in mammalian organisms. Investigations of the circadian clock-DNA damage response connections have revealed that nucleotide excision repair, DNA damage checkpoints, and apoptosis are appreciably influenced by the clock. Although several epidemiological studies in humans and a limited number of genetic studies in mouse model systems have indicated that clock disruption may predispose mammals to cancer, well-controlled genetic studies in mice have not supported the commonly held view that circadian clock disruption is a cancer risk factor. In fact, in the appropriate genetic background, clock disruption may instead aid in cancer regression by promoting intrinsic and extrinsic apoptosis. Finally, the clock may affect the efficacy of cancer treatment (chronochemotherapy) by modulating the pharmacokinetics and pharmacodynamics of chemotherapeutic drugs as well as the activity of the DNA repair enzymes that repair the DNA damage caused by anticancer drugs.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina School of Medicine , Chapel Hill, North Carolina 27599, United States.
authors.forename: Aziz
authors.initials: A
authors.lastname: Sancar
authors.forename: Laura A
authors.initials: LA
authors.lastname: Lindsey-Boltz
authors.forename: Shobhan
authors.initials: S
authors.lastname: Gaddameedhi
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Selby
authors.forename: Rui
authors.initials: R
authors.lastname: Ye
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Chiou
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kemp
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Hu
authors.forename: Jin Hyup
authors.initials: JH
authors.lastname: Lee
authors.forename: Nuri
authors.initials: N
authors.lastname: Ozturk
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D057906:Circadian Clocks; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D045643:DNA Repair Enzymes / Q000378:metabolism; D055870:Drug Chronotherapy; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D045643:DNA Repair Enzymes