Watching the clock in glioblastoma

Neuro-Oncology, Год журнала: 2023, Номер 25(11), С. 1932 - 1946

Опубликована: Июнь 16, 2023

Abstract Glioblastoma (GBM) is the most prevalent malignant primary brain tumor, accounting for 14.2% of all diagnosed tumors and 50.1% tumors, median survival time approximately 8 months irrespective whether a patient receives treatment without significant improvement despite expansive research (Ostrom QT, Price M, Neff C, et al. CBTRUS statistical report: other central nervous system in United States 2015–2019. Neurooncology. 2022; 24(suppl 5):v1–v95.). Recently, important roles circadian clock GBM tumorigenesis have been reported. Positive regulators circadian-controlled transcription, muscle ARNT-like 1 (BMAL1), locomotor output cycles kaput (CLOCK), are highly expressed also correlated with poor prognosis. BMAL1 CLOCK promote maintenance stem cells (GSCs) establishment pro-tumorigenic tumor microenvironment (TME), suggesting that targeting core proteins may augment treatment. Here, we review findings highlight critical role plays biology strategies by which can be leveraged clinic moving forward.

Язык: Английский

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Chronoradiobiology of Breast Cancer: The Time Is Now to Link Circadian Rhythm and Radiation Biology

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1331 - 1331

Опубликована: Янв. 25, 2022

Circadian disruption has been linked to cancer development, progression, and radiation response. Clinical evidence date shows that circadian genetic variation time of treatment affect response toxicity for women with breast cancer. At the molecular level, there is interplay between clock regulators such as PER1, which mediates ATM p53-mediated cell cycle gating apoptosis. These alterations may govern aggressive phenotypes, outcomes, Exploiting various mechanisms enhance therapeutic index by decreasing toxicity, increasing disease control, improving outcomes. We will review body's natural rhythms gene-regulation while exploring preclinical clinical implicates chronobiological disruptions in etiology discuss radiobiological principles regulation DNA damage responses. Lastly, we present potential rational approaches target pathways improve outcomes Understanding implications optimal timing ways entrain biology light, diet, agents like melatonin provide an avenue enhancing radiotherapy.

Язык: Английский

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XRCC1: a potential prognostic and immunological biomarker in LGG based on systematic pan-cancer analysis

Aging, Год журнала: 2024, Номер unknown

Опубликована: Янв. 12, 2024

X-ray repair cross-complementation group 1 (XRCC1) is a pivotal contributor to base excision repair, and its dysregulation has been implicated in the oncogenicity of various human malignancies. However, comprehensive pan-cancer analysis investigating prognostic value, immunological functions, epigenetic associations XRCC1 remains lacking. To address this knowledge gap, we conducted systematic investigation employing bioinformatics techniques across 33 cancer types. Our encompassed expression levels, diagnostic implications, profiles, immune molecular subtypes, Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), checkpoints, infiltration, leveraging data from TCGA, GTEx, CELL, Human Protein Atlas, Ualcan, cBioPortal databases. Notably, displayed both positive negative correlations with prognosis different tumors. Epigenetic revealed between DNA methylation patterns 10 types, as well enhanced phosphorylation. Furthermore, demonstrated TMB MSI majority Interestingly, gene exhibited correlation cell infiltration except for M1 M2 macrophages monocytes most cancers. Additionally, observed significant checkpoint levels. Lastly, our findings replication processes, shedding light on precise mechanisms underlying oncogenic effects. Overall, study highlights potential biomarker, thereby offering novel target tumor immunotherapy.

Язык: Английский

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Chronobiologie in der Onkologie: Onkologische Therapien am besten zur individuell optimalen Tageszeit

Deutsches Ärzteblatt, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

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Personalization of Cancer Treatment: Exploring the Role of Chronotherapy in Immune Checkpoint Inhibitor Efficacy

Cancers, Год журнала: 2025, Номер 17(5), С. 732 - 732

Опубликована: Фев. 21, 2025

In the era of precision medicine, mounting evidence suggests that time therapy administration, or chronotherapy, has a great impact on treatment outcomes. Chronotherapy involves planning timing by considering circadian rhythms, which are 24 h oscillations in behavior and physiology driven synchronized molecular clocks throughout body. The value chronotherapy cancer is currently under investigation, notably effects efficacy side effects. Immune checkpoint inhibitor (ICI) promising treatment. However, many patients still experience disease progression need to stop early due There accumulating day at ICI administered can have substantial effect efficacy. Thus, it important investigate intersections this review, we provide brief overview rhythms context immunity cancer. Additionally, outline current applications for We synthesize 29 studies conducted date examine time-of-day administration therapy, its associated effects, sex differences both also discuss potential mechanisms underlying these observed results. Finally, highlight challenges area future directions research, including chronotherapeutic personalized medicine approach tailors individual patients’ rhythms.

Язык: Английский

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The Interrelationship Between Circadian Rhythms and Sleep Quality: Mechanisms, Influencing Factors, and Therapeutic Approaches

Advances in Psychology, Год журнала: 2025, Номер 15(04), С. 111 - 118

Опубликована: Янв. 1, 2025

Язык: Английский

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The Impact of Genetic Variations on Radiotherapy Toxicity in Breast Cancer Patients: A Meta-Analysis of Acute and Late Skin Adverse Effects

Cancers, Год журнала: 2025, Номер 17(11), С. 1880 - 1880

Опубликована: Июнь 4, 2025

Background/Objectives: Radiotherapy is a cornerstone in the treatment of breast cancer, yet its use frequently accompanied by skin toxicities that vary severity and timing among patients. The objective this meta-analysis to systematically evaluate pooled impact genetic variations on risk acute late side effects from radiotherapy cancer Materials Methods: A systematic literature search was conducted across PubMed, Embase, Scopus identify studies published between 2014 2024 examined associations polymorphisms radiotherapy-induced toxicity. Studies were selected based predefined inclusion exclusion criteria, data synthesized using random-effects model. bias evaluated ROBINS-I tool, publication assessed through funnel plots Egger’s test. Results: total 11 involving patients included, identifying various gene analysis revealed with specific variants had 53% increased 44% effects. Notable implicated genes included XRCC2, IFNG, ATM, TGFB1, PER3. Significant heterogeneity noted studies, warranting cautious interpretation. Conclusions: This highlights role variation predicting toxicity These findings support future development predictive biomarkers personalized strategies minimize treatment-related

Язык: Английский

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Chronotherapeutics for Solid Tumors

Pharmaceutics, Год журнала: 2023, Номер 15(8), С. 2023 - 2023

Опубликована: Июль 26, 2023

Circadian rhythms are internal manifestations of the 24-h solar day that allow for synchronization biological and behavioral processes to external day. This precise regulation physiology behavior improves adaptive function survival. Chronotherapy takes advantage circadian in physiological optimize timing drug administration achieve maximal therapeutic efficacy minimize negative side effects. cancer treatment was first demonstrated be beneficial more than five decades ago has favorable effects across diverse types. However, implementation chronotherapy clinic remains limited. The present review examines evidence chronotherapeutic solid tumors. Specifically, studies examining chrono-chemotherapy, chrono-radiotherapy, alternative chronotherapeutics (e.g., hormone therapy, TKIs, antiangiogenic immunotherapy) discussed. In addition, we propose areas needed research identify challenges field remain addressed.

Язык: Английский

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Temporal Considerations in Brain Metastases Radiation Therapy: The Intersection of Chronobiology and Patient Profiles

Опубликована: Янв. 24, 2024

Background: The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assesses timing's impact on whole-brain radiotherapy outcomes in brain metastases personalized therapy insights. Aim: Evaluate influence radiation timing its correlation with clinical outcomes. Identify patient populations benefiting from interventions synchronizing rhythms, considering subgroup differences potential disparities related to social determinants of health (SDoH). Design: IRB-approved retrospective analysis 237 patients undergoing (2017–2021), receiving over 80% treatments the morning or afternoon. Survival analyses utilized Kaplan–Meier curves. Setting/Participants: Single-institution involving radiotherapy. Collected demographic, disease, socioeconomic parameters electronic medical records. Results: Morning (n=158) showed trend towards improved overall survival vs. afternoon (n=79), median 158 79 days (p=0.20, HR=0.84, CI95% 0.84–0.91). Subgroup benefits females (p=0.04) trends controlled primary disease (p=0.11) breast (p=0.08). SDoH-based observed, Black lower-income exhibiting diminished influence. Conclusions: Emphasizes chronobiological factors' relevance therapy. correlates survival, particularly specific subgroups. Identifies based SDoH, laying foundation rhythms enhanced efficacy.

Язык: Английский

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Impact of Circadian Rhythms on the Development and Clinical Management of Genitourinary Cancers

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Март 9, 2022

The circadian system is an innate clock mechanism that governs biological processes on a near 24-hour cycle. Circadian rhythm disruption (i.e., misalignment of rhythms), which results from the lack synchrony between master located in suprachiasmatic nuclei (SCN) and environment exposure to day light) or peripheral clocks, has been associated with increased risk unfavorable cancer outcomes. Growing evidence supports link prevalence mortality genitourinary cancers (GU) including prostate, bladder, renal cancer. also plays essential role timely implementation chronopharmacological treatments, such as melatonin chronotherapy, reduce tumor progression, improve therapeutic response negative therapy side effects. potential benefits manipulating rhythms clinical setting GU detection treatment remain be exploited. In this review, we discuss current influence (disease) development hope elucidate unmet need defining extensive involvement predicting for alleviating burden implementing anti-cancer therapies.

Язык: Английский

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