ArticleJournal of neuro-oncology2024
Circadian regulation of MGMT expression and promoter methylation underlies daily rhythms in TMZ sensitivity in glioblastoma.
Article in Journal of neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Advances in monitoring mammalian circadian components and their rhythms using reporter systems.RSC chemical biology · 2026Review
- Label-Free Raman Spectroscopy Reveals Metabolic Signatures Associated with MGMT Promoter Methylation Status in Glioblastoma.Analytical chemistry · 2026Article
- Design considerations for hypertension chronotherapy trials: insights from experience and modelling.BMC medicine · 2026Review
- The Potential of Chronotherapy and Nanotherapy-Based Strategies for Glioblastoma Treatment.Pharmaceutics · 2026Review
- Daily locomotor activity declines with tumor growth and disease progression in glioblastoma.JCI insight · 2026Article
- Personalized chronotherapy in glioblastoma: integrating circadian profiling and PK-PD modelling to optimize temozolomide timing.NPJ precision oncology · 2025Article
- Article
- Circadian variation in MGMT promoter methylation and expression predicts sensitivity to temozolomide in glioblastoma.Journal of neuro-oncology · 2025Article
- Circadian rhythms in pediatric high-grade gliomas may contribute to treatment efficacy.Scientific reports · 2025Article
- Tracking Daily Variations in Rest-Wake to Guide Personalized Timing of Temozolomide for High-Grade Glioma Patients.Journal of biological rhythms · 2025Article
- Circadian-Tuned Peptide Drug/Gene Co-Delivery Nanocomplexes to Enhance Glioblastoma Targeting and Transfection.International journal of molecular sciences · 2025Article
- Correlation between levels of clock protein expression and effects on temozolomide-resistant glioblastoma and tumor progression.Human cell · 2025Article
- Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host.Cancer cell · 2025Article
- Stressing the importance of circadian time in treatment responses.Cancer cell · 2025Article
- Pharmacological Modulation of the Cytosolic Oscillator Affects Glioblastoma Cell Biology.Cellular and molecular neurobiology · 2024Article
- Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host.bioRxiv : the preprint server for biology · 2024Article
- Chronobiology of the Tumor Microenvironment: Implications for Therapeutic Strategies and Circadian-Based Interventions.Aging and disease · 2024Review
- Two decades of progress in glioma methylation research: the rise of temozolomide resistance and immunotherapy insights.Frontiers in neuroscience · 2024Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundGlioblastoma (GBM) is the most common primary brain tumor in adults. Despite extensive research and clinical trials, median survival post-treatment remains at 15 months. Thus, all opportunities to optimize current treatments and improve patient outcomes should be considered. A recent retrospective clinical study found that taking TMZ in the morning compared to the evening was associated with a 6-month increase in median survival in patients with MGMT-methylated GBM. Here, we hypothesized that TMZ efficacy depends on time-of-day and O METHODS AND
resultsIn vitro recordings using real-time bioluminescence reporters revealed that GBM cells have intrinsic circadian rhythms in the expression of the core circadian clock genes Bmal1 and Per2, as well as in the DNA repair enzyme, MGMT. Independent measures of MGMT transcript levels and promoter methylation also showed daily rhythms intrinsic to GBM cells. These cells were more susceptible to TMZ when delivered at the daily peak of Bmal1 transcription. We found that in vivo morning administration of TMZ also decreased tumor size and increased body weight compared to evening drug delivery in mice bearing GBM xenografts. Finally, inhibition of MGMT activity with O
conclusionWe conclude that chemotherapy with TMZ can be dramatically enhanced by delivering at the daily maximum of tumor Bmal1 expression and minimum of MGMT activity and that scoring MGMT methylation status requires controlling for time of day of biopsy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.