Biological rhythms impact all facets of life, including the hour we wake up and how our body metabolizes food. The research paper “Overlapping Central Clock Network Circuitry Regulates Circadian Feeding and Activity Rhythms in Drosophila” by Saurabh et al. centers on the brain's central circadian clock, which is responsible for feeding and activity patterns in Drosophila melanogaster, showcasing the intricate neural circuits that preserve homeostasis between various bodily functions. Interactions among dopaminergic signals from clock neurons produce rhythmic behaviors, exhibiting the complex boundary of circadian regulation. His research reveals the contribution of overlapping neural networks to these rhythms, and how, in turn, the feeding activity of the organism is synchronized with its internal clock.
His studies may be centered on fruit flies, but the implications reach well outside of entomology. Human biological systems are also driven by circadian rhythms, more so, in the context of disease. One fascinating example stems from oncology, since the development, progression, and treatments of cancer all depend on circadian rhythm. The research paper titled “Circadian Rhythms and Cancer: Implications for Timing in Therapy” by El-Tanani et al. discusses the importance of time in cancer therapies, such as chemotherapy and radiation. The paper also explores various ways to enhance treatment efficacy. Circadian biology and the timing of cancer treatment are interlinked, which is why it is important to treat patients in a way that optimizes therapeutic outcomes and quality of life while minimal side effects.
The research done by Saurabh et al. focuses on subsets of Drosophila circadian neurons and interactions between them during locomotion and feeding. The fly’s brain consists of two different groups of neurons called DN1p and LNv. These neurons seem to have distinct but related roles in the regulation of circadian behaviors. Notably, LNv neurons primarily regulate locomotor activities through pigment-dispersing factor (PDF) transmission, while DN1p neurons control feeding cycles through insulin signaling. The researchers also discuss how network disruptions result in unfed and unmoved states, which are similar to the consequences of dysregulation in the circadian systems of humans with diseases, such as cancer and metabolic syndromes.
Similarly, the Circadian Rhythms and Cancer paper demonstrates the effects of circadian rhythm misalignment in oncology, which is now common among shift workers and individuals with irregular sleeping patterns. Misalignment can significantly disrupt cellular homeostasis, which contributes towards tumorigenesis. The article discusses two major tumor-suppressing oncogenes, p53 and Myc. These genes are regulated by the circadian clock, suggesting that disruption of clocks is a significant factor in cancer development. However, in chemotherapy, the timing of drug administration has a major influence on both the drugs’ toxicity to the host and their metabolism. Experiments utilizing the chemotherapeutic drug cisplatin have demonstrated that the time of its use impacts both its effectiveness and side effects. When cisplatin is used in conjunction with the body’s circadian rhythms, the best results are achieved.
Chronotherapy, which is the timing of when to administer treatment to maximize its effects, is one of the most fascinating areas of circadian research. Specifically, Saurabh et al.’s research on the importance of synchronous neural control of feeding provides key information about how circadian rhythms modulate metabolic processes. This information is important for cancer treatment, since metabolism is critical to absorption and disposition of drugs.
The Circadian Rhythms and Cancer study provides concrete evidence that correct timing of treatment enhances results. It is clinically proven that the timing of chemotherapy influences the ability of healthy cells to tolerate treatment. For example, patients with colorectal cancer who have been given 5-fluorouracil (5-FU) and oxaliplatin through chronomodulated administration report improvements in tolerance and fewer side effects.
The goal of Saurabh et al.’s study serves as an important piece of the puzzle in understanding how circadian rhythms control physiological processes. Their research forms a foundation for investigating the homologous mechanisms in humans through the characterization of neural circuitry responsible for feeding and locomotion in flies. In light of the connection between circadian rhythms and cancer treatment timing, future research should aim at defining optimal times to treat various cancers, which could completely redefine oncology management.
As the intricacies of circadian rhythms are better understood by researchers, collaborative research between oncologists and chronobiologists can lead to targeted medicine approaches based on synchronizing treatment regimens with patients' own internal clocks. Combining data from clinical studies of cancer treatment with data derived from model organisms, such as Drosophila, can lead to novel directions of inquiry into enhancing patient outcome and reducing side effects of treatment, ultimately leading to life-saving developments in cancer treatment and demonstrating the extraordinary interrelatedness of circadian biology across species.
References
El-Tanani, M., Rabbani, S.A., Ali, A.A. et al. (2024). Circadian rhythms and cancer: implications for timing in therapy. Discov Onc, 15, 767. https://doi.org/10.1007/s12672-024-01643-4
Saurabh, S., Meier, R. J., Pireva, L. M., Mirza, R. A., & Cavanaugh, D. J. (2024). Overlapping Central Clock Network Circuitry Regulates Circadian Feeding and Activity Rhythms in Drosophila. Journal of biological rhythms, 39(5), 440–462. https://doi.org/10.1177/07487304241263734
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