Watching the clock in glioblastoma

Jun 16, 2023Neuro-oncology

Timing and Progression in Glioblastoma Brain Tumors

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Glioblastoma () accounts for 14.2% of all diagnosed tumors and 50.1% of all malignant tumors, with a median survival time of approximately 8 months.

Positive regulators of the circadian clock, BMAL1 and CLOCK, are highly expressed in GBM and correlate with poor patient outcomes.
These proteins contribute to the maintenance of GBM stem cells and create a tumor microenvironment that supports cancer growth.
Targeting BMAL1 and CLOCK may enhance treatment strategies for GBM.

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

Key numbers

80%–90%

Proportion of tumors with TERT mutations

TERT mutations occur in the majority of cases.

8 months

Survival time without treatment

Median survival time for patients is approximately 8 months.

50.1%

prevalence among malignant brain tumors

accounts for over half of all malignant brain tumors.

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Watching the clock in glioblastoma

Abstract

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