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

Gonzalez-Aponte, Maria F.; Damato, Anna R.; Trebucq, Laura Lucía; Simon, Tatiana; Cárdenas-García, Sandra P.; Cho, Kevin; Patti, Gary J.; Golombek, Diego A.; Chiesa, Juan José; Rubin, Joshua B.; Herzog, Erik D.

doi:10.1007/s11060-023-04535-9

Cited by 3 publications

References 42 publications

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Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host

Gonzalez-Aponte,

Damato,

Simon

et al. 2024

Preprint

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Glioblastoma (GBM) is the most common primary brain tumor in adults with a poor prognosis despite aggressive therapy. A recent, retrospective clinical study found that administering Temozolomide in the morning increased patient overall survival by 6 months compared to evening. Here, we tested the hypothesis that daily host signaling regulates tumor growth and synchronizes circadian rhythms in GBM. We found daily Dexamethasone promoted or suppressed GBM growth depending on time of day of administration and on the clock gene, Bmal1. Blocking circadian signals, like VIP or glucocorticoids, dramatically slowed GBM growth and disease progression. Finally, mouse and human GBM models have intrinsic circadian rhythms in clock gene expression in vitro and in vivo that entrain to the host through glucocorticoid signaling, regardless of tumor type or host immune status. We conclude that GBM entrains to the circadian circuit of the brain, which modulates its growth through clock-controlled cues, like glucocorticoids.

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Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host

Gonzalez-Aponte,

Damato,

Simon

et al. 2024

Preprint

Self Cite

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Chronobiology of the Tumor Microenvironment: Implications for Therapeutic Strategies and Circadian-Based Interventions

Li,

Yu,

et al. 2024

Aging and disease

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Numerous research works have emphasized the critical role that circadian rhythm plays in the tumor microenvironment (TME). The goal of clarifying chrono-pharmacological strategies for improving cancer treatment in clinical settings is a continuous endeavor. Consequently, to enhance the use of time-based pharmaceutical therapies in oncology, combining existing knowledge on circadian rhythms' roles within the TME is essential. This perspective elucidates the functions of circadian rhythms in the TME across various stages of cancer development, progression, and metastasis. Specifically, aging, angiogenesis, and inflammation are implicated in modulating circadian rhythm within the TME. Furthermore, circadian rhythm exerts a profound influence on current cancer treatments and thereby generates chronotheray to manage tumors. From a TME perspective, circadian rhythm offers promising opportunities for cancer prevention and treatment; nevertheless, further study is needed to address unanswered scientific problems.

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Daily Glucocorticoids Promote Glioblastoma Growth and Circadian Synchrony to the Host

Gonzalez-Aponte,

Damato,

Simon

et al. 2024

Preprint

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

Cited by 3 publications

References 42 publications

Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host

Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host

Chronobiology of the Tumor Microenvironment: Implications for Therapeutic Strategies and Circadian-Based Interventions

Daily Glucocorticoids Promote Glioblastoma Growth and Circadian Synchrony to the Host

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