Circadian clock, cancer, and chemotherapy

Biochemistry. 2015 Jan 20;54(2):110-23. doi: 10.1021/bi5007354. Epub 2014 Oct 29.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Circadian Clocks*
  • DNA Damage / drug effects
  • DNA Repair / drug effects
  • DNA Repair Enzymes / metabolism
  • Drug Chronotherapy
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / epidemiology
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Risk Factors


  • Antineoplastic Agents
  • DNA Repair Enzymes