New Insights Into Cancer Chronotherapies

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 13, 2021

Circadian clocks participate in the coordination of various metabolic and biological activities to maintain homeostasis. Disturbances circadian rhythm cancers are closely related. clock genes differentially expressed many tumors, accelerate development progression tumors. In addition, tumor tissues exert varying compared normal due resetting altered rhythms. Thus, chronotherapeutics used for cancer treatment should exploit timing rhythms achieve higher efficacy mild toxicity. Due interpatient differences functions, our findings advocate an individualized precision approach chronotherapy. Herein, we review specific association between cancers. focus on chronotherapies personalized biomarkers The understanding will provide a rationale more effective clinical

Language: Английский

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Differences in toxicity and outcome associated with circadian variations between patients undergoing daytime and evening radiotherapy for prostate adenocarcinoma

Chronobiology International, Journal Year: 2016, Volume and Issue: 33(2), P. 210 - 219

Published: Jan. 28, 2016

This retrospective study tested the hypothesis that disease control and treatment-related toxicity in patients undergoing high-dose radiotherapy (HDRT) for prostate cancer varies a circadian manner. Patients with localized adenocarcinoma receiving HDRT (median 78 Gy) to involved seminal vesicle(s) without elective pelvic irradiation were divided into daytime treatment (before 5 PM) group (n = 267) evening (after 142). Biochemical failure (Phoenix definition), acute late gastrointestinal (GI) genitourinary toxicities (Common Terminology Criteria Adverse Events version 4), biochemical failure-free survival (BFFS) freedom from assessed. Analyses performed by binary logistic regression Cox proportional hazard regression. The median follow-up was 68 months, 75% of ≥70 years old. Evening significantly associated worse ≥grade 2 GI complications (hazard ratio 2.96; p < 0.001). detrimental effect significant older than 70 old (p 0.001) but not younger 0.63). In subgroup propensity score-matched cohort T2b-T3 154), 5-year BFFS (72% vs. 85%, 1.95, 0.05). Our indicates may lead more complications, especially patients, disease.

Language: Английский

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Timing gone awry: distinct tumour suppressive and oncogenic roles of the circadian clock and crosstalk with hypoxia signalling in diverse malignancies

Journal of Translational Medicine, Journal Year: 2019, Volume and Issue: 17(1)

Published: April 23, 2019

The circadian clock governs a large variety of fundamentally important physiological processes in all three domains life. Consequently, asynchrony timekeeping mechanisms could give rise to cellular dysfunction underpinning many disease pathologies including human neoplasms. Yet, detailed pan-cancer evidence supporting this notion has been limited.In an integrated approach uniting genomic, transcriptomic and clinical data 21 cancer types (n = 18,484), we interrogated copy number transcript profiles 32 genes identify putative loss-of-function (ClockLoss) gain-of-function (ClockGain) players. Kaplan-Meier, Cox regression receiver operating characteristic analyses were employed evaluate the prognostic significance both gene sets.ClockLoss ClockGain associated with tumour-suppressing tumour-promoting roles respectively. Downregulation ClockLoss resulted significantly higher mortality rates five cohorts 2914): bladder (P 0.027), glioma < 0.0001), pan-kidney 0.011), clear cell renal 0.0001) stomach 0.0007). In contrast, patients high expression oncogenic had poorer survival outcomes 2784): 0.0034), 0.014), lung 0.046) pancreas 0.0059). Both sets independent other clinicopathological features permit further delineation tumours within same stage. Circadian reprogramming tumour genomes activation numerous pathways those stem cells, suggesting that may influence self-renewal mechanisms. Within hypoxic microenvironment, dysregulation is exacerbated by hypoxia glioma, renal, pancreatic cancers, resulting additional death risks. Tumour suppressive negatively correlated inducible factor-1A targets patients, providing novel framework for investigating hypoxia-clock signalling axis.Loss fidelity promotes progression influences outcomes. offer druggable improving patient prognosis. can be used stratification adjuvant chronotherapy treatment. Emerging interactions between harnessed achieve therapeutic advantage using hypoxia-modifying compounds combination first-line treatments.

Language: Английский

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An Optimal Time for Treatment—Predicting Circadian Time by Machine Learning and Mathematical Modelling

Cancers, Journal Year: 2020, Volume and Issue: 12(11), P. 3103 - 3103

Published: Oct. 23, 2020

Tailoring medical interventions to a particular patient and pathology has been termed personalized medicine. The outcome of cancer treatments is improved when the intervention timed in accordance with patient’s internal time. Yet, one challenge medicine how consider biological time patient. Prerequisite for this so-called chronotherapy an accurate characterization circadian As alternative time-consuming measurements sleep-laboratory, recent studies chronobiology predict by applying machine learning approaches mathematical modelling easier accessible observables such as gene expression. Embedding these results into dynamics between clock mammals, we review precision predictions potential usage respect treatment discuss whether observables, may provide additional indication individualized timing. Besides health improvement, timing imply financial advantages, ameliorating side effects treatments, thus reducing costs. Summarizing advances years, brings together current clinical standard measuring time, general assessment rhythmicity, rhythmic variables models rhythmicity.

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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