Circadian Regulation of Drug Responses: Toward Sex-Specific and Personalized Chronotherapy

被引:36
作者
Levi, Francis A. [1 ,2 ,3 ]
Okyar, Alper [4 ]
Hadadi, Eva [5 ,6 ]
Innominato, Pasquale F. [7 ,8 ,9 ]
Ballesta, Annabelle [10 ]
机构
[1] Paris Saclay Univ, Chronotherapy Canc & Transplantat Res Unit, Fac Med, Villejuif, France
[2] Hop Paul Brousse, Assistance Publ Hop Paris, Gastrointestinal & Gen Oncol Serv, Villejuif, France
[3] Univ Warwick, Dept Stat, Coventry, W Midlands, England
[4] Istanbul Univ, Dept Pharmacol, Fac Pharm, Istanbul, Turkiye
[5] Vrije Univ Brussel, Lab Cellular & Mol Immunol, Brussels, Belgium
[6] Ctr Inflammat Res VIB, Lab Myeloid Cell Immunol, Zwijnaarde, Belgium
[7] Betsi Cadwaladr Univ Hlth Board, Ysbyty Gwynedd Hosp, Dept Oncol, Bangor, Wales
[8] Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England
[9] Univ Warwick, Canc Res Ctr, Coventry, W Midlands, England
[10] PSL Res Univ, Inserm Unit 900, Canc Syst Pharmacol, Inst Curie,MINES ParisTech,CBIO Ctr Computat Biol, St Cloud, France
关键词
circadian rhythms; chronopharmacology; chronotherapy; sex specificity; precision medicine; between-subjects variability; METASTATIC COLORECTAL-CANCER; P-GLYCOPROTEIN EXPRESSION; COENZYME-A REDUCTASE; OF-DAY INFUSION; PHASE-II TRIAL; SMALL-MOLECULE; FOLINIC ACID; DOSING-TIME; ACETAMINOPHEN HEPATOTOXICITY; TRANSCRIPTION FACTORS;
D O I
10.1146/annurev-pharmtox-051920-095416
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Today's challenge for precision medicine involves the integration of the impact of molecular clocks on drug pharmacokinetics, toxicity, and efficacy toward personalized chronotherapy. Meaningful improvements of tolerability and/or efficacy of medications through proper administration timing have been confirmed over the past decade for immunotherapy and chemotherapy against cancer, as well as for commonly used pharmacological agents in cardiovascular, metabolic, inflammatory, and neurological conditions. Experimental and human studies have recently revealed sexually dimorphic circadian drug responses. Dedicated randomized clinical trials should now aim to issue personalized circadian timing recommendations for daily medical practice, integrating innovative technologies for remote longitudinal monitoring of circadian metrics, statistical prediction of molecular clock function from single-timepoint biopsies, and multiscale biorhythmic mathematical modelling. Importantly, chronofit patients with a robust circadian function, who would benefit most from personalized chronotherapy, need to be identified. Conversely, nonchronofit patients could benefit from the emerging pharmacological class of chronobiotics targeting the circadian clock.
引用
收藏
页码:89 / 114
页数:26
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