Evidence map›Paper›PMID 40909807›Full record

ArticleResearch square2025

Circadian variation in MGMT promoter methylation and expression predicts sensitivity to Temozolomide in glioblastoma.

Maria F Gonzalez-Aponte, Yitong Huang, William A Leidig, Tatiana Simon, Omar H Butt, Marc D Ruben, Albert H Kim, Joshua B Rubin, Erik D Herzog, Olivia J Walch

Abstract readPreprint
In one paragraph

Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Maria F Gonzalez-AponteDepartment of Biology, Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO, 63130, USA.ORCID 0000-0002-8139-312X
Yitong HuangDepartment of Mathematical Sciences, Smith College, MA, 01063, USA.ORCID 0000-0002-5200-8077
William A LeidigDepartment of Neurosurgery, Washington University School of Medicine, St Louis, Missouri, USA.ORCID 0009-0008-3127-3905
Tatiana SimonDepartment of Biology, Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO, 63130, USA.ORCID 0000-0001-5686-8798
Omar H ButtDivision of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA.ORCID 0000-0003-2252-3673
Marc D RubenDivisions of Pulmonary Medicine and Biomedical Informatics, Cincinnati Children's Hospital, USA.ORCID 0000-0002-7893-0238
Albert H KimDepartment of Neurosurgery, Washington University School of Medicine, St Louis, Missouri, USA.ORCID 0000-0002-1751-8493
Joshua B RubinDepartment of Pediatrics, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, MO, 63110, USA.ORCID 0000-0002-7395-1937
Erik D HerzogDepartment of Biology, Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO, 63130, USA.ORCID 0000-0001-7209-5174
Olivia J WalchArcascope Inc., Arlington, VA, 22203, USA.ORCID 0000-0002-7881-6910

Funding

MAXIMIZING STUDENT DIVERSITY IN THE BIOMEDICAL SCIENCES AT WASHINGTON UNIVERSITYR25GM103757 · NIGMS · WASHINGTON UNIVERSITY · PI SKEATH, JAMES BENJAMIN · 2013 to 2022
$4.5M
Neuroscience Training Program at Washington UniversityT32NS121881 · NINDS · WASHINGTON UNIVERSITY · PI Martha W Bagnall, Daniel Kerschensteiner · 2021 to 2026
$3.1M
Mechanisms of SOX2 Regulation in GlioblastomaR01NS128470 · NINDS · WASHINGTON UNIVERSITY · PI Albert Hong-Jae Kim · 2022 to 2026
$1.9M
Circadian interventions against glioblastomaR01NS134885 · NINDS · WASHINGTON UNIVERSITY · PI Erik Herzog, Joshua B Rubin · 2024 to 2026
$1.3M
Chronotherapy for glioblastomaR21NS120003 · NINDS · WASHINGTON UNIVERSITY · PI HERZOG, ERIK, RUBIN, JOSHUA B · 2021 to 2022
$433k
NIGMS NIH HHS R25 GM103757NINDS NIH HHS R01 NS128470NINDS NIH HHS R01 NS134885NINDS NIH HHS R21 NS120003NINDS NIH HHS T32 NS121881
6 · The paper itself

Abstract

Purpose: Recent studies show that glioblastoma (GBM) is more sensitive to Temozolomide (TMZ) in the morning. In cells, inhibiting O6-Methylguanine-DNA-Methyltransferase (MGMT) abolished time-dependent TMZ efficacy, suggesting that circadian regulation of this DNA repair enzyme underlies daily TMZ sensitivity. Here, we tested the hypotheses that MGMT-promoter methylation and protein abundance vary with time-of-day in GBM, resulting in daily rhythms in TMZ efficacy. Methods: We assessed daily rhythms in Results: We found daily rhythms in Conclusion: Our findings suggest that the likelihood of diagnosis of MGMT-promoter methylation varies with time of biopsy in GBM. Furthermore, we predict that efforts to deliver TMZ after the daily peak of MGMT activity, with exact time being dose-dependent, will significantly enhance its therapeutic efficacy.

Indexed as

ChronodiagnosisChronotherapyGBMMGMT expression and promoter methylationTMZ

Identifiers

PMID40909807
PMCPMC12408013

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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.