Molecular Aspects of Circadian Pharmacology and Relevance for Cancer Chronotherapy

Ozturk N., Ozturk D., Kavakli I. H., Okyar A.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol.18, no.10, 2017 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 18 Issue: 10
  • Publication Date: 2017
  • Doi Number: 10.3390/ijms18102168
  • Journal Name: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: biological rhythms, circadian timing system (CTS), chronopharmacodynamics, chronopharmacokinetics, cancer chronotherapy, DIHYDROPYRIMIDINE DEHYDROGENASE-ACTIVITY, METASTATIC COLORECTAL-CANCER, GLUTATHIONE-S-TRANSFERASE, CELL-CYCLE REGULATION, SLEEP PHASE SYNDROME, GROWTH-FACTOR, CLOCK GENES, DOSING-TIME, THYMIDYLATE SYNTHASE, DRUG-DELIVERY
  • Istanbul University Affiliated: Yes

Abstract

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.