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Cancers
Special Issues
Circadian Rhythms, Cancers and Chronotherapy
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Circadian Rhythms, Cancers and Chronotherapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 31 March 2025 | Viewed by 11209

Special Issue Editors

Prof. Dr. Francis Levi

E-Mail Website
Guest Editor
1. UPR “Chronotherapy, Cancer and Transplantation”, Medical School, Paris-Saclay University, 94800 Villejuif, France
2. Cancer Chronotherapy Team, Cancer Research Centre, Division of Biomedical Sciences, Warwick Medical School, Coventry CV4 7AL, UK
3. Centre Hépato Biliaire, AP-HP, Hôpital Paul Brousse (APHP), 94800 Villejuif, France
Interests: circadian clocks; biological rhythms; chronopharmacology; chronotherapy; gastro-intestinal oncology; biomakers; digital health
Dr. Pasquale F. Innominato

E-Mail Website
Guest Editor
1. Oncology Department, Ysbyty Gwynedd, Betsi Cadwaladr University Health Board, Bangor LL57 2PW, UK
2. Cancer Research Centre, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
3. UPR “Chronotherapy, Cancers and Transplantation”, Faculty of Medicine, Paris-Saclay University, 94800 Villejuif, France
Interests: cancer chronotherapeutics; circadian rhythms; supportive care; digital health
Dr. Esra Tasali

E-Mail Website
Guest Editor
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Interests: sleep and circadian rhythms; sleep disorders; energy metabolism

Special Issue Information

Dear Colleagues,

This Special Issue on “Circadian rhythms, Cancers and Chronotherapy” aims at advancing precision and personalized cancer medicine. Toward such goal, we are pleased to invite you to submit original or review scientific or biomedical articles on these topics. We welcome original contributions reporting new challenging scientific results and/or highlighting novel approaches regarding the molecular, cellular, and physiologic interactions between circadian rhythms and cancer processes and treatments, as well as their healthcare implications. Indeed, a hierarchical network of cellular clocks, consisting of a system of 15 clock genes, orchestrates cellular metabolism, proliferation, and survival, as well as physiology and responses to therapeutic agents, over a 24 h timescale. Accumulating evidence supports an important role of circadian rhythms both for carcinogenesis processes from initiation to progression and metastasis, and for the tolerability and efficacy of all kinds of cancer treatments. However, circadian rhythms can differ as a function of sex, age, environment, genetics, or other biological factors in experimental cancer models, among people at risk of cancer, and among cancer patients. Manuscripts on the relevance of circadian or other biological clocks in the following research areas may include (but are not limited to):

  • In vitro and in vivo experimental cancer models
  • Drug development and chronotherapy
  • Chemotherapy, immunotherapy, targeted agents, radiotherapy, surgery
  • Circadian host or tumor biomarkers
  • Electronic patient-reported outcomes
  • Circadian rhythms and sleep
  • Sex- and age specificities
  • Clinical trial designs
  • Mathematical models and artificial intelligence
  • Digital healthcare, telemedicine, logistics

We look forward to receiving your contributions.

Prof. Dr. Francis Levi
Dr. Pasquale F. Innominato
Dr. Esra Tasali
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • circadian rhythms
  • clock genes
  • carcinogenesis
  • chronotherapy, biomarkers
  • patient-reported outcomes
  • sleep
  • sex
  • precision oncology
  • artificial intelligence

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Published Papers (5 papers)

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Research

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20 pages, 1719 KiB  
Article
Variances in the Expression Profile of Circadian Clock-Related Genes in Astrocytic Brain Tumors
by Rafał Staszkiewicz, Dawid Sobański, Wojciech Pulka, Dorian Gładysz, Marcin Gadzieliński, Damian Strojny and Beniamin Oskar Grabarek
Cancers 2024, 16(13), 2335; https://doi.org/10.3390/cancers16132335 - 26 Jun 2024
Viewed by 2196
Abstract
This study explores the role of circadian clock genes in the progression of astrocytic tumors, a prevalent type of brain tumor. The aim was to assess the expression patterns of these genes in relation to the tumor grade. Using microarray analysis, qRT-PCR, and [...] Read more.
This study explores the role of circadian clock genes in the progression of astrocytic tumors, a prevalent type of brain tumor. The aim was to assess the expression patterns of these genes in relation to the tumor grade. Using microarray analysis, qRT-PCR, and methylation-specific PCR, we examined gene expression, DNA methylation patterns, and microRNA interactions in tumor samples from 60 patients. Our results indicate that the expression of key circadian clock genes, such as clock circadian regulator (CLOCK), protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2), protein kinase AMP-activated non-catalytic subunit beta 1 (PRKAB1), protein kinase AMP-activated non-catalytic subunit beta 2 (PRKAB2), period circadian regulator 1 (PER1), period circadian regulator 2 (PER2) and period circadian regulator 3 (PER3), varies significantly with the tumor grade. Notably, increased CLOCK gene expression and protein levels were observed in higher-grade tumors. DNA methylation analysis revealed that the promoter regions of PER1-3 genes were consistently methylated, suggesting a mechanism for their reduced expression. Our findings also underscore the complex regulatory mechanisms involving miRNAs, such as hsa-miR-106-5p, hsa-miR-20b-5p, and hsa-miR-30d-3p, which impact the expression of circadian clock-related genes. This underscores the importance of circadian clock genes in astrocytic tumor progression and highlights their potential as biomarkers and therapeutic targets. Further research is needed to validate these results and explore their clinical implications. Full article
(This article belongs to the Special Issue Circadian Rhythms, Cancers and Chronotherapy)
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17 pages, 13335 KiB  
Article
Time-Restricted Feeding Attenuates Metabolic Dysfunction-Associated Steatohepatitis and Hepatocellular Carcinoma in Obese Male Mice
by Manasi Das, Deepak Kumar, Consuelo Sauceda, Alexis Oberg, Lesley G. Ellies, Liping Zeng, Lily J. Jih, Isabel G. Newton and Nicholas J. G. Webster
Cancers 2024, 16(8), 1513; https://doi.org/10.3390/cancers16081513 - 16 Apr 2024
Cited by 3 | Viewed by 2398
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) has surpassed the hepatitis B virus and hepatitis C virus as the leading cause of chronic liver disease in most parts of the Western world. MASLD (formerly known as NAFLD) encompasses both simple steatosis and more aggressive [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has surpassed the hepatitis B virus and hepatitis C virus as the leading cause of chronic liver disease in most parts of the Western world. MASLD (formerly known as NAFLD) encompasses both simple steatosis and more aggressive metabolic dysfunction-associated steatohepatitis (MASH), which is accompanied by inflammation, fibrosis, and cirrhosis, and ultimately can lead to hepatocellular carcinoma (HCC). There are currently very few approved therapies for MASH. Weight loss strategies such as caloric restriction can ameliorate the harmful metabolic effect of MASH and inhibit HCC; however, it is difficult to implement and maintain in daily life, especially in individuals diagnosed with HCC. In this study, we tested a time-restricted feeding (TRF) nutritional intervention in mouse models of MASH and HCC. We show that TRF abrogated metabolic dysregulation induced by a Western diet without any calorie restriction or weight loss. TRF improved insulin sensitivity and reduced hyperinsulinemia, liver steatosis, inflammation, and fibrosis. Importantly, TRF inhibited liver tumors in two mouse models of obesity-driven HCC. Our data suggest that TRF is likely to be effective in abrogating MASH and HCC and warrant further studies of time-restricted eating in humans with MASH who are at higher risk of developing HCC. Full article
(This article belongs to the Special Issue Circadian Rhythms, Cancers and Chronotherapy)
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14 pages, 275 KiB  
Article
Rotating Night Shift Work, Sleep, and Thyroid Cancer Risk in the Nurses’ Health Study 2
by Kyriaki Papantoniou, Peter Konrad, Shahab Haghayegh, Susanne Strohmaier, A. Heather Eliassen and Eva Schernhammer
Cancers 2023, 15(23), 5673; https://doi.org/10.3390/cancers15235673 - 30 Nov 2023
Cited by 6 | Viewed by 2757
Abstract
Night shift work has been associated with breast, prostate, and colorectal cancer, but evidence on other types of cancer is limited. We prospectively evaluated the association of rotating night shift work, sleep duration, and sleep difficulty with thyroid cancer risk in the Nurses’ [...] Read more.
Night shift work has been associated with breast, prostate, and colorectal cancer, but evidence on other types of cancer is limited. We prospectively evaluated the association of rotating night shift work, sleep duration, and sleep difficulty with thyroid cancer risk in the Nurses’ Health Study 2 (NHS2). We assessed rotating night shift work duration (years) at baseline and throughout follow-up (1989–2015) and sleep characteristics in 2001. Cox proportional hazard models, adjusted for potential confounders, were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for (a) shift work duration, (b) sleep duration, and (c) difficulty falling or staying asleep. We stratified the analyses of night shift work by sleep duration and sleep difficulty. Over 26 years of follow-up, 588 incident cases were identified among 114,534 women in the NHS2 cohort. We observed no association between night shift work and the risk of thyroid cancer. Difficulty falling or staying asleep was suggestively associated with a higher incidence of thyroid cancer when reported sometimes (HR 1.26, 95% CI 0.95, 1.66) and all or most of the time (HR 1.35, 95% CI 1.00, 1.81). Night shift workers (10+ years) with sleep difficulty all or most of the time (HR 1.47; 0.58–3.73) or with >7 h of sleep duration (HR 2.17; 95% CI, 1.21–3.92) had a higher risk of thyroid cancer. We found modest evidence for an increased risk of thyroid cancer in relation to sleep difficulty, which was more pronounced among night shift workers. Full article
(This article belongs to the Special Issue Circadian Rhythms, Cancers and Chronotherapy)

Review

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31 pages, 7387 KiB  
Review
Impact of Modern Lifestyle on Circadian Health and Its Contribution to Adipogenesis and Cancer Risk
by Oxana Dobrovinskaya, Javier Alamilla and Miguel Olivas-Aguirre
Cancers 2024, 16(21), 3706; https://doi.org/10.3390/cancers16213706 - 1 Nov 2024
Viewed by 1677
Abstract
Background: Recent research underscores a crucial connection between circadian rhythm disruption and cancer promotion, highlighting an urgent need for attention. Objectives: Explore the molecular mechanisms by which modern lifestyle factors—such as artificial light exposure, shift work, and dietary patterns—affect cortisol/melatonin regulation and cancer [...] Read more.
Background: Recent research underscores a crucial connection between circadian rhythm disruption and cancer promotion, highlighting an urgent need for attention. Objectives: Explore the molecular mechanisms by which modern lifestyle factors—such as artificial light exposure, shift work, and dietary patterns—affect cortisol/melatonin regulation and cancer risk. Methods: Employing a narrative review approach, we synthesized findings from Scopus, Google Scholar, and PubMed to analyze lifestyle impacts on circadian health, focusing on cortisol and melatonin chronobiology as molecular markers. We included studies that documented quantitative changes in these markers due to modern lifestyle habits, excluding those lacking quantitative data or presenting inconclusive results. Subsequent sections focused solely on articles that quantified the effects of circadian disruption on adipogenesis and tumor microenvironment modifications. Results: This review shows how modern habits lead to molecular changes in cortisol and melatonin, creating adipose microenvironments that support cancer development. These disruptions facilitate immune evasion, chemotherapy resistance, and tumor growth, highlighting the critical roles of cortisol dysregulation and melatonin imbalance. Conclusions: Through the presented findings, we establish a causal link between circadian rhythm dysregulation and the promotion of certain cancer types. By elucidating this relationship, the study emphasizes the importance of addressing lifestyle factors that contribute to circadian misalignment, suggesting that targeted interventions could play a crucial role in mitigating cancer risk and improving overall health outcomes. Full article
(This article belongs to the Special Issue Circadian Rhythms, Cancers and Chronotherapy)
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14 pages, 1497 KiB  
Review
Chronobiology of Cancers in the Liver and Gut
by Jessica M. Ferrell
Cancers 2024, 16(17), 2925; https://doi.org/10.3390/cancers16172925 - 23 Aug 2024
Viewed by 1187
Abstract
Circadian rhythms dictate the timing of cellular and organismal physiology to maintain homeostasis. Within the liver and gut, circadian rhythms influence lipid and glucose homeostasis, xenobiotic metabolism, and nutrient absorption. Disruption of this orchestrated timing is known to negatively impact human health and [...] Read more.
Circadian rhythms dictate the timing of cellular and organismal physiology to maintain homeostasis. Within the liver and gut, circadian rhythms influence lipid and glucose homeostasis, xenobiotic metabolism, and nutrient absorption. Disruption of this orchestrated timing is known to negatively impact human health and contribute to disease progression, including carcinogenesis. Dysfunctional core clock timing has been identified in malignant growths and may be used as a molecular signature of disease progression. Likewise, the circadian clock and its downstream effectors also represent potential for novel therapeutic targets. Here, the role of circadian rhythms in the pathogenesis of cancers of the liver and gut will be reviewed, and chronotherapy and chronopharmacology will be explored as potential treatment options. Full article
(This article belongs to the Special Issue Circadian Rhythms, Cancers and Chronotherapy)
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