Article Impact Level: HIGH Data Quality: STRONG Summary of Cancer Cell, S1535610824004471. https://doi.org/10.1016/j.ccell.2024.11.012 Dr. Maria F. Gonzalez-Aponte et al.
Points
- Glioblastoma (GBM) tumor growth and gene expression exhibit daily rhythms synchronized with the host’s circadian clock, influenced by glucocorticoid signaling.
- Daily glucocorticoid fluctuations can promote or suppress GBM growth, depending on the time of day, with glucocorticoid receptor (GR) signaling playing a central role.
- In mouse models, morning administration of dexamethasone increased tumor size, while evening administration suppressed growth; lower GR expression in human GBM tumors correlated with a 60% longer patient survival rate.
- Tailoring treatment timing to align with individual circadian rhythms could optimize the efficacy of cancer therapies and minimize the risk of tumor progression due to glucocorticoid treatment.
- The study underscores the need for circadian-based interventions in GBM treatment, emphasizing personalized therapy timing based on tumor-specific and patient-specific circadian rhythms.
Summary
A recent study investigates the role of circadian rhythms and glucocorticoids in glioblastoma (GBM) progression and treatment outcomes. GBM, a highly aggressive brain tumor, has been shown to exhibit daily rhythms in tumor growth and gene expression, which are synchronized with the host’s circadian clock. The study reveals that daily glucocorticoid fluctuations influence tumor progression by modulating clock gene expression in cancer cells. Specifically, glucocorticoids promote or suppress GBM growth depending on the time of day, with glucocorticoid receptor (GR) signaling playing a key role in this process. The study found that blocking circadian signals such as glucocorticoid release dramatically slows GBM growth and disease progression in murine models.
Using a mouse model of glioblastoma, the researchers observed that the timing of glucocorticoid administration significantly influenced tumor growth. Administering the synthetic glucocorticoid dexamethasone (DEX) in the morning resulted in a significant increase in tumor size compared to evening administration, which suppressed tumor growth. Additionally, the presence of glucocorticoid receptor expression in human GBM tumors was linked to worse outcomes, with patients exhibiting a 60% longer survival rate when tumors expressed lower levels of the receptor. These findings suggest that circadian synchronization of therapy could optimize treatment efficacy and potentially prevent tumor progression associated with glucocorticoid treatment.
The study highlights the potential of chronotherapy, which tailors treatment timing based on individual circadian rhythms, to enhance the effectiveness of cancer therapies. This research suggests that timing glucocorticoid administration could improve patient outcomes in GBM, particularly by minimizing the risk of exacerbating tumor growth. The findings pave the way for future clinical trials exploring circadian-based cancer treatment interventions, emphasizing the need for personalized timing of therapies based on tumor-specific and patient-specific circadian rhythms.
Link to the article: https://www.cell.com/cancer-cell/fulltext/S1535-6108(24)00447-1
References Gonzalez-Aponte, M. F., Damato, A. R., Simon, T., Aripova, N., Darby, F., Jeon, M. S., Luo, J., Rubin, J. B., & Herzog, E. D. (2024). Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host. Cancer Cell, S1535610824004471. https://doi.org/10.1016/j.ccell.2024.11.012
