Time to fight: targeting the circadian clock molecular machinery in cancer therapy

Drug Discov Today. 2021 May;26(5):1164-1184. doi: 10.1016/j.drudis.2021.01.023. Epub 2021 Feb 4.


The circadian clock regulates a wide range of molecular pathways and biological processes. The expression of clock genes is often altered in cancer, fostering tumor initiation and progression. Inhibition and activation of core circadian clock genes, as well as treatments that restore circadian rhythmicity, have been successful in counteracting tumor growth in different experimental models. Here, we provide an up-to-date overview of studies that show the therapeutic effects of targeting the clock molecular machinery in cancer, both genetically and pharmacologically. We also highlight future areas for progress that offer a promising path towards innovative anticancer strategies. Substantial limitations in the current understanding of the complex interplay between the circadian clock and cancer in vivo need to be addressed in order to allow clock-targeting therapies in cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Circadian Clocks / genetics*
  • Circadian Rhythm / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Neoplasms / therapy*