Metastasis is the most common event that determines survival in patients with breast cancer. The benefits of appropriate sleep in enhancing cancer patients' prognosis have been demonstrated. Likewise, emerging evidence has noted the positive impacts of regular circadian rhythm on cancer survival. Proper sleep and regular circadian rhythm can help to improve the cancer prognosis by enhancing the immune system. Besides, circadian rhythm disruption can assist cancer progression by promoting systemic inflammation. However, a recent study by Diamantopoulou et al. titled “The Metastatic Spread of Breast Cancer Accelerates during Sleep” demonstrated that sleep can aggravate breast cancer metastasis. This article outlines how the study design can affect this controversy.

http://journal.waocp.org/article_90512_7b7352bc67336a1dc562f3e6de65eb69.pdf

The Metastatic Spread of Breast Cancer Accelerates during Sleep: How the Study Design can Affect the Results

The molecular machinery of the circadian clock regulates the expression of many genes and processes in the organism, allowing the adaptation of cellular activities to the daily light-dark cycles. Disruption of the circadian rhythm can lead to various pathologies, including cancer. Thus, disturbance of the normal circadian clock at both genetic and environmental levels has been described as an independent risk factor for cancer. In addition, researchers have proposed that circadian genes may have a tissue-dependent and/or context-dependent role in tumorigenesis and may function both as tumor suppressors and oncogenes. Finally, circadian clock core genes may trigger or at least be involved in different hallmarks of cancer. Hence, expanding the knowledge of the molecular basis of the circadian clock would be helpful to identify new prognostic markers of tumorigenesis and potential therapeutic targets. 

Interactions of circadian clock genes with the hallmarks of cancer.

Developmental impact of peripheral injury on neuroimmune signaling

Chronic liver diseases including hepatocellular carcinoma (HCC) create a state of chronic inflammation that affects the brain via the liver–brain axis leading to an alteration of neurotransmission and cognition. However, little is known about the effects of HCC on the hippocampus, the key brain region for learning and memory. Moreover, radiotherapy used to treat HCC has severe side effects that impair patients’ life quality. Thus, designing optimal strategies, such as chronotherapy, to enhance the efficacy and reduce the side effects of HCC treatment is critically important. We addressed the effects of HCC and the timed administration of radiotherapy in mice on the expression of pro-inflammatory cytokines, clock genes, markers for glial activation, oxidative stress, neuronal activity and proliferation in the hippocampal neurogenic niche. Our data showed that HCC induced the upregulation of genes encoding for pro-inflammatory cytokines, altered clock gene expressions and reduced proliferation in the hippocampus. Radiotherapy, in particular when applied during the light/inactive phase enhanced all these effects in addition to glial activation, increased oxidative stress, decreased neuronal activity and increased levels of phospho(p)-ERK. Our results suggested an interaction of the circadian molecular clockwork and the brain’s innate immune system as key players in liver–brain crosstalk in HCC and that radiotherapy when applied during the light/inactive phase induced the most profound alterations in the hippocampus.

/pdf/radiotherapy-of-the-hepatocellular-carcinoma-in-mice-has-a-3rvd9if0.pdf

Radiotherapy of the Hepatocellular Carcinoma in Mice Has a Time-Of-Day-Dependent Impact on the Mouse Hippocampus

These cancer cells wake up when people sleep.

https://doi.org/10.1016/j.bbih.2022.100428

Sophie Debs

Papers

Disrupting circadian rhythms promotes cancer-induced inflammation in mice

Pain-resolving immune mechanisms in neuropathic pain