Personalized chronotherapy in glioblastoma: integrating circadian profiling and PK-PD modelling to optimize temozolomide timing.

ABSTRACT: Glioblastoma (GBM) remains one of the most lethal brain tumors, with limited benefit from current standard therapies, including temozolomide (TMZ). Chronotherapy-aligning treatment with the circadian clock-has shown improved cancer outcomes, but its clinical efficacy in GBM remains inconsistent, potentially due to a lack of personalization. Here, we present an integrated experimental and computational approach to investigate personalized TMZ chronotherapy. Using a GBM in vitro model, along with genetic and pharmacological manipulation of clock genes (BMAL1, NR1D1, PER2), we show that TMZ sensitivity is time-of-day dependent. Clock gene disruption reduced TMZ efficacy, likely through altered DNA repair regulation. Co-treatment with clock modulators modulated TMZ response dependent on clock

SUBMITTER: Nelson N 

PROVIDER: S-EPMC12796165 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature