Roles of circadian clocks in cancer pathogenesis and treatment

Experimental & Molecular Medicine, Journal Year: 2021, Volume and Issue: 53(10), P. 1529 - 1538

Published: Oct. 1, 2021

Abstract Circadian clocks are ubiquitous timing mechanisms that generate approximately 24-h rhythms in cellular and bodily functions across nearly all living species. These internal clock systems enable organisms to anticipate respond daily changes their environment a timely manner, optimizing temporal physiology behaviors. Dysregulation of circadian by genetic environmental risk factors increases susceptibility multiple diseases, particularly cancers. A growing number studies have revealed dynamic crosstalk between cancer pathways, providing mechanistic insights into the therapeutic utility treatment. This review will discuss roles pathogenesis, highlighting recent advances chronotherapeutic approaches for improved

Language: Английский

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Circadian rhythms and cancers: the intrinsic links and therapeutic potentials

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: March 4, 2022

The circadian rhythm is an evolutionarily conserved time-keeping system that comprises a wide variety of processes including sleep-wake cycles, eating-fasting and activity-rest coordinating the behavior physiology all organs for whole-body homeostasis. Acute disruption may lead to transient discomfort, whereas long-term irregular will result in dysfunction organism, therefore increasing risks numerous diseases especially cancers. Indeed, both epidemiological experimental evidence has demonstrated intrinsic link between dysregulated cancer. Accordingly, rapidly understanding molecular mechanisms rhythms opening new options cancer therapy, possibly by modulating clock. In this review, we first describe general regulators their functions on addition, provide insights into underlying how several types (including sleep-wake, eating-fasting, activity-rest) can drive progression, which expand our development from clock perspective. Moreover, also summarize potential applications treatment, optional therapeutic strategy patients.

Language: Английский

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Circadian Rhythms, Disease and Chronotherapy

Journal of Biological Rhythms, Journal Year: 2021, Volume and Issue: 36(6), P. 503 - 531

Published: Sept. 22, 2021

Circadian clocks are biological timing mechanisms that generate 24-h rhythms of physiology and behavior, exemplified by cycles sleep/wake, hormone release, metabolism. The adaptive value is evident when internal body daily environmental mismatched, such as in the case shift work jet lag or even mistimed eating, all which associated with physiological disruption disease. Studies animal human models have also unraveled an important role functional circadian modulating cellular organismal responses to cues (ex., food intake, exercise), pathological insults (e.g. virus parasite infections), medical interventions medication). With growing knowledge molecular underlying pathophysiology, it becoming possible target for disease prevention treatment. In this review, we discuss recent advances research potential therapeutic applications take patient into account treating

Language: Английский

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Inorganic–inorganic nanohybrids for drug delivery, imaging and photo-therapy: recent developments and future scope

Chemical Science, Journal Year: 2021, Volume and Issue: 12(14), P. 5044 - 5063

Published: Jan. 1, 2021

The present review will be detailing about trending inorganic–inorganic nanohybrids that have been used for various biomedical applications including drug-delivery, bio-imaging and photo therapy.

Language: Английский

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Disrupting Circadian Rhythm via the PER1–HK2 Axis Reverses Trastuzumab Resistance in Gastric Cancer

Cancer Research, Journal Year: 2022, Volume and Issue: 82(8), P. 1503 - 1517

Published: March 7, 2022

Trastuzumab is the only approved targeted drug for first-line treatment of HER2-positive advanced gastric cancer, but high rate primary resistance and rapid emergence secondary limit its clinical benefits. We found that trastuzumab-resistant (TR) cancer cells exhibited glycolytic activity, which was controlled by hexokinase 2 (HK2)-dependent glycolysis with a circadian pattern [higher at zeitgeber time (ZT) 6, lower ZT18]. Mechanistically, HK2 oscillation regulated transcriptional complex composed PPARγ core clock gene PER1. In vivo in vitro experiments demonstrated silencing PER1 disrupted rhythm PER1-HK2 reversed trastuzumab resistance. Moreover, metformin, inhibits PER1, combined ZT6, significantly improved efficacy cancer. Collectively, these data introduce into therapy propose potentially effective chronotherapy strategy to reverse cancer.In fluctuates BMAL1-CLOCK-PER1-HK2 axis, can be metformin-based overcome

Language: Английский

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Chronotherapy in Glioblastoma: state of the art and future perspectives

EBioMedicine, Journal Year: 2023, Volume and Issue: 89, P. 104470 - 104470

Published: Feb. 15, 2023

Language: Английский

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A mathematical model of the circadian clock and drug pharmacology to optimize irinotecan administration timing in colorectal cancer

Computational and Structural Biotechnology Journal, Journal Year: 2021, Volume and Issue: 19, P. 5170 - 5183

Published: Jan. 1, 2021

Scheduling anticancer drug administration over 24 h may critically impact treatment success in a patient-specific manner. Here, we address personalization of timing using novel mathematical model irinotecan cellular pharmacokinetics and –dynamics linked to representation the core clock predict toxicity colorectal cancer (CRC) model. The is fitted three different scenarios: mouse liver, where metabolism mainly occurs, two human cell lines representing an vitro experimental system for progression. Our successfully recapitulates quantitative circadian datasets mRNA protein expression together with timing-dependent cytotoxicity data. also discriminates time-dependent between cells, suggesting that can be optimized according their clock. results show degradation mediating activation, as well oscillation death rate play important role variations toxicity. In future, this used support personalized scheduling by predicting optimal based on patient's gene profile.

Language: Английский

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Association of Circadian Timing of Initial Infusions of Immune Checkpoint Inhibitors with Survival in Advanced Melanoma

Immunotherapy, Journal Year: 2023, Volume and Issue: 15(11), P. 819 - 826

Published: May 16, 2023

Aims: Chronomodulation of immune checkpoint inhibitors (ICIs) is not well understood. The authors evaluated the circadian timing initial ICI infusions. Patients & methods: A retrospective cohort study patients with advanced melanoma (n = 121) was conducted. Results: Exclusive afternoon first four infusions associated worse overall survival (5.5 vs 24.9 months; p < 0.001) and progression-free (3.3 7.6 0.009) on Kaplan–Meier curves. In multivariable Cox analysis, rate lower in who received all versus ≥1 morning (hazard ratio: 2.4; 0.004). Conclusion: Deliberate scheduling for several treatments may improve patient-centered outcomes.

Language: Английский

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A perspective on emerging therapies in metastatic colorectal cancer: Focusing on molecular medicine and drug resistance

Cell Biochemistry and Function, Journal Year: 2024, Volume and Issue: 42(1)

Published: Jan. 1, 2024

Abstract The majority of cancer cases are colorectal cancer, which is also the second largest cause cancer‐related deaths worldwide. Metastasis leading death for patients with cancer. Metastatic incidence on rise due to a tiny percentage tumors developing resistant medicines despite advances in treatment tactics. Cutting‐edge targeted medications now go‐to option customized and all‐encompassing CRC care. Specifically, multitarget kinase inhibitors, antivascular endothelial growth factors, epidermal factor receptors widely used clinical practice CRC‐targeted treatments. Rare targets metastatic becoming more well‐known developments precision diagnostics extensive use second‐generation sequencing technology. These include KRAS mutation, BRAF V600E HER2 overexpression/amplification, MSI‐H/dMMR. Incorporating certain into trials has significantly increased patient survival rates, opening new avenues bringing fresh viewpoints treating focused therapies change how treated, giving hope better results. markers can transform individualize therapy regimens. They could open door precisely effective medicines, improving outcomes quality life. fast‐growing body knowledge regarding molecular biology latest gene directly responsible this advancement.

Language: Английский

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Shaping the future of precision oncology: Integrating circadian medicine and mathematical models for personalized cancer treatment

Current Opinion in Systems Biology, Journal Year: 2024, Volume and Issue: 37, P. 100506 - 100506

Published: Feb. 29, 2024

The growing numbers of cancer cases represent a medical and societal burden worldwide. More than half all patients are treated with chemotherapy. Yet, chemotherapeutic drugs kill not only cells, but also healthy tissue, causing massive adverse side effects. Recent research on circadian medicine suggests that side-effects can be reduced, treatment efficacy increased, by considering the biological clock patients. Integrating profiles molecular markers in personalized mathematical models simulate individual dynamics drug uptake, action cellular response to This requires advanced computational tools balance prediction quality overfitting. Personalized will eventually lead an optimal alignment timing inner patient, reducing effects, increasing enhancing patient well-being.

Language: Английский

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