Roles of circadian clocks in cancer pathogenesis and treatment

Experimental & Molecular Medicine, Год журнала: 2021, Номер 53(10), С. 1529 - 1538

Опубликована: Окт. 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

Язык: Английский

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Circadian rhythms and cancers: the intrinsic links and therapeutic potentials

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Март 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.

Язык: Английский

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Circadian Rhythms, Disease and Chronotherapy

Journal of Biological Rhythms, Год журнала: 2021, Номер 36(6), С. 503 - 531

Опубликована: Сен. 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

Язык: Английский

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

Chemical Science, Год журнала: 2021, Номер 12(14), С. 5044 - 5063

Опубликована: Янв. 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.

Язык: Английский

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

Cancer Research, Год журнала: 2022, Номер 82(8), С. 1503 - 1517

Опубликована: Март 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

Язык: Английский

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Chronotherapy in Glioblastoma: state of the art and future perspectives

EBioMedicine, Год журнала: 2023, Номер 89, С. 104470 - 104470

Опубликована: Фев. 15, 2023

Язык: 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, Год журнала: 2021, Номер 19, С. 5170 - 5183

Опубликована: Янв. 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.

Язык: Английский

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

Immunotherapy, Год журнала: 2023, Номер 15(11), С. 819 - 826

Опубликована: Май 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.

Язык: 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, Год журнала: 2024, Номер 37, С. 100506 - 100506

Опубликована: Фев. 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.

Язык: Английский

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Circadian clock as a possible control point in colorectal cancer progression (Review)

International Journal of Oncology, Год журнала: 2022, Номер 61(6)

Опубликована: Окт. 17, 2022

The circadian rhythm is generated at the cellular level by a molecular clock system that involves specific genes. Studies have revealed disruption control point in cancer progression. Colorectal (CRC) one of cancers closely associated with disruption. In present review, involvement CRC development was summarized. Abnormal expression certain genes has been found patients and their correlation clinicopathological features also explored. period cryptochrome 2 (Cry2), Sirtuin1 (SIRT1) neuronal PAS domain protein (NPAS2) were reported to tumour suppressor properties. Conversely, Cry1, brain muscle ARNT‑like‑1, locomotor output cycles kaput (CLOCK) timeless may aggravate progression, but these findings are not consistent require be confirmed further research. Circadian scheduling indicated advantages chemotherapy treatments for increasing maximum tolerated doses decreasing toxicities. Dysfunction CLOCK disrupted processes accelerate colon tumorigenesis, such as metabolism, cell cycle, DNA damage repair, proliferation apoptosis, epithelial‑mesenchymal transition stemness. gene network how dynamics influence discussed.

Язык: Английский

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