The dynamic control of signal transduction networks in cancer cells

Nature reviews. Cancer, Journal Year: 2015, Volume and Issue: 15(9), P. 515 - 527

Published: Aug. 20, 2015

Language: Английский

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Systems Chronotherapeutics

Pharmacological Reviews, Journal Year: 2017, Volume and Issue: 69(2), P. 161 - 199

Published: March 28, 2017

Chronotherapeutics aim at treating illnesses according to the endogenous biologic rhythms, which moderate xenobiotic metabolism and cellular drug response. The molecular clocks present in individual cells involve approximately fifteen clock genes interconnected regulatory feedback loops. They are coordinated by suprachiasmatic nuclei, a hypothalamic pacemaker, also adjusts circadian rhythms environmental cycles. As result, many mechanisms of diseases effects controlled timing system. Thus, tolerability nearly 500 medications varies up fivefold scheduling, both experimental models and/or patients. Moreover, treatment itself disrupted, maintained, or improved system as function timing. Improved patient outcomes on circadian-based treatments (chronotherapy) have been demonstrated randomized clinical trials, especially for cancer inflammatory diseases. However, recent technological advances highlighted large interpatient differences functions resulting significant variability chronotherapy Such findings advocate advancement personalized chronotherapeutics through interdisciplinary systems approaches. combination mathematical, statistical, technological, experimental, expertise is now shaping development dedicated devices diagnostic delivery algorithms enabling individualization. In particular, multiscale chronopharmacology approaches currently combine mathematical modeling based whole-body physiology preclinical investigations toward design patient-tailored chronotherapies. We review research works aiming individualization disease treatment, with emphasis management system–resetting strategies improving chronic control outcomes.

Language: Английский

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The Genomic Landscape and Pharmacogenomic Interactions of Clock Genes in Cancer Chronotherapy

Cell Systems, Journal Year: 2018, Volume and Issue: 6(3), P. 314 - 328.e2

Published: March 1, 2018

Language: Английский

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Dosing-Time Makes the Poison: Circadian Regulation and Pharmacotherapy

Trends in Molecular Medicine, Journal Year: 2016, Volume and Issue: 22(5), P. 430 - 445

Published: April 5, 2016

Language: Английский

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The circadian timing system in clinical oncology

Annals of Medicine, Journal Year: 2014, Volume and Issue: 46(4), P. 191 - 207

Published: June 1, 2014

The circadian timing system (CTS) controls several critical molecular pathways for cancer processes and treatment effects over the 24 hours, including drug metabolism, cell cycle, apoptosis, DNA damage repair mechanisms. This results in time dependency of whole-body cellular pharmacokinetics pharmacodynamics anticancer agents. However, CTS robustness phase varies among patients, based on monitoring rest– activity, body temperature, sleep, and/or hormonal secretion rhythms. Circadian disruption has been further found up to 50% patients with metastatic cancer. Such was associated poor outcomes, fatigue, anorexia, sleep disorders, short progression-free overall survival. Novel, minimally invasive devices have enabled continuous assessment non-hospitalized patients. They revealed 12-hour differences individual phase. Taken together, data support personalization chronotherapy. method aims at adjustment delivery according rhythms, using programmable-in-time pumps or novel release formulations, order increase both efficacy tolerability. A fixed oxaliplatin, 5-fluorouracil leucovorin chronotherapy protocol prolonged median survival men colorectal by 3.3 months as compared conventional delivery, a meta-analysis (P = 0.009). Further analyses need prevention restoration robust function chronotherapy, optimize effects. strengthening external synchronizers could meet such goal, through programmed exercise, meal timing, light exposure, improved social support, scheduling, properly timed administration drugs that target clocks. Chrono-rehabilitation warrants clinical testing improving quality life

Language: Английский

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Disrupted seasonal biology impacts health, food security and ecosystems

Proceedings of the Royal Society B Biological Sciences, Journal Year: 2015, Volume and Issue: 282(1817), P. 20151453 - 20151453

Published: Oct. 15, 2015

The rhythm of life on earth is shaped by seasonal changes in the environment. Plants and animals show profound annual cycles physiology, health, morphology, behaviour demography response to environmental cues. Seasonal biology impacts ecosystems agriculture, with consequences for humans biodiversity. Human populations robust rhythms health well-being, birth month can have lasting effects that persist throughout life. This review emphasizes need a better understanding against backdrop its rapidly progressing disruption through climate change, human lifestyles other anthropogenic impact. Climate change modifying which numerous organisms adapted, potential industries relating food security. Disconcertingly, under artificial conditions eternal summer provide most extreme example disconnect from natural seasons, making vulnerable increased morbidity mortality. In this review, we introduce scenarios disruption, highlight key aspects summarize biomedical, anthropological, veterinary, agricultural perspectives recent evidence desynchronization between factors internal rhythms. Because are pervasive across biological systems, they common framework trans-disciplinary research.

Language: Английский

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Circadian clocks, epigenetics, and cancer

Current Opinion in Oncology, Journal Year: 2014, Volume and Issue: 27(1), P. 50 - 56

Published: Nov. 15, 2014

Purpose of review The interplay between circadian rhythm and cancer has been suggested for more than a decade based on the observations that shift work incidence are linked. Accumulating evidence implicates clock in survival proliferation pathways. At molecular level, multiple control mechanisms have proposed to link transcription cell-cycle tumorigenesis. Recent findings gating cell cycle subsequent is an area active investigation. Moreover, transcriptional system intricately regulated at epigenetic level. Interestingly, landscape level histone modifications, DNA methylation, small regulatory RNAs differentially controlled cells. This concept raises possibility common thread linking with cancer, though little scientific known date. Summary focuses speculates possible connections could further tumor initiation or progression.

Language: Английский

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Circadian Clock Gene Bmal1 Inhibits Tumorigenesis and Increases Paclitaxel Sensitivity in Tongue Squamous Cell Carcinoma

Cancer Research, Journal Year: 2016, Volume and Issue: 77(2), P. 532 - 544

Published: Nov. 8, 2016

Circadian clock genes regulate cancer development and chemotherapy susceptibility. Accordingly, chronotherapy based on circadian phenotypes might be applied to improve therapeutic efficacy. In this study, we investigated whether the gene Bmal1 inhibited tumor increased paclitaxel sensitivity in tongue squamous cell carcinoma (TSCC). expression was downregulated its rhythmic pattern of affected TSCC samples lines. Ectopic proliferation, migration invasion vitro, growth mouse xenograft models TSCC. After exposure paclitaxel, Bmal1-overexpressing cells displayed a relative increase apoptosis were more susceptible treatment vivo Mechanistic investigations suggested regulatory connection between Bmal1, TERT, oncogenic transcriptional repressor EZH2 (enhancer zeste homolog 2), recruitment which TERT promoter paclitaxel-induced inhibition. Clinically, efficacy correlated positively with levels Overall, our results identified as novel suppressor that elevates potential implications timing biomarker Cancer Res; 77(2); 532-44. ©2016 AACR.

Language: Английский

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Circadian rhythm in pharmacokinetics and its relevance to chronotherapy

Biochemical Pharmacology, Journal Year: 2020, Volume and Issue: 178, P. 114045 - 114045

Published: May 22, 2020

Language: Английский

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The Circadian Clock and Viral Infections

Journal of Biological Rhythms, Journal Year: 2020, Volume and Issue: 36(1), P. 9 - 22

Published: Nov. 9, 2020

The circadian clock controls several aspects of mammalian physiology and orchestrates the daily oscillations biological processes behavior. Our rhythms are driven by an endogenous central in brain that synchronizes with clocks peripheral tissues, thereby regulating our immune system severity infections. These affect pharmacokinetics efficacy therapeutic agents vaccines. core regulatory circuits clock-regulated host pathways provide fertile ground to identify novel antiviral therapies. An increased understanding role systems play virus infection response will inform clinical management these diseases. This review provides overview experimental evidence reporting on interplay between viral infections, highlighting importance virus-clock research.

Language: Английский

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