Circadian regulation of MGMT expression and promoter methylation underlies daily rhythms in TMZ sensitivity in glioblastoma.

ABSTRACT:

Background

Glioblastoma (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 O⁶-Methylguanine-DNA Methyltransferase (MGMT) activity in murine and human models of GBM.

Methods and results

In vitro recordings using real-time bioluminescence reporters revealed that GBM cells have intrinsic circadian rhyt

SUBMITTER: Gonzalez-Aponte MF 

PROVIDER: S-EPMC11301575 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature