Molecular Aspects of Circadian Pharmacology and Relevance for Cancer Chronotherapy

• Published in: International journal of molecular sciences Vol. 18; no. 10; p. 2168
• Main Authors: Ozturk, Narin, Ozturk, Dilek, Kavakli, Ibrahim Halil, Okyar, Alper
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.10.2017; MDPI
• Subjects: Angiogenesis; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antitumor activity; Apoptosis; biological rhythms; Cancer; cancer chronotherapy; Cell cycle; chronopharmacodynamics; chronopharmacokinetics; Circadian Clocks - drug effects; Circadian rhythm; Circadian Rhythm - drug effects; Circadian Rhythm - physiology; Circadian rhythms; circadian timing system (CTS); Detoxification; Drug Chronotherapy; Drug Delivery Systems; Drug-Related Side Effects and Adverse Reactions; Drugs; Genomes; Humans; Immunosuppressive agents; Metabolism; Neoplasms - drug therapy; Pharmacology; Review; Toxicity; chronopharmacokinetics; cancer chronotherapy; biological rhythms; chronopharmacodynamics; circadian timing system (CTS)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18102168

The circadian timing system (CTS) controls various biological functions in mammals including xenobiotic metabolism and detoxification, immune functions, cell cycle events, apoptosis and angiogenesis. Although the importance of the CTS is well known in the pharmacology of drugs, it is less appreciated at the clinical level. Genome-wide studies highlighted that the majority of drug target genes are controlled by CTS. This suggests that chronotherapeutic approaches should be taken for many drugs to enhance their effectiveness. Currently chronotherapeutic approaches are successfully applied in the treatment of different types of cancers. The chronotherapy approach has improved the tolerability and antitumor efficacy of anticancer drugs both in experimental animals and in cancer patients. Thus, chronobiological studies have been of importance in determining the most appropriate time of administration of anticancer agents to minimize their side effects or toxicity and enhance treatment efficacy, so as to optimize the therapeutic ratio. This review focuses on the underlying mechanisms of the circadian pharmacology i.e., chronopharmacokinetics and chronopharmacodynamics of anticancer agents with the molecular aspects, and provides an overview of chronotherapy in cancer and some of the recent advances in the development of chronopharmaceutics.