4.6 Review

Sleep Disruption and Cancer: Chicken or the Egg?

Journal

FRONTIERS IN NEUROSCIENCE
Volume 16, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2022.856235

Keywords

sleep disruption; cancer; anti-tumor immunity; stress; inflammation; HPA axis; sympathetic nervous system; hypocretin; orexin

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Sleep plays a crucial role in evolutionary fitness, and chronic disruption of sleep can lead to various physiological problems, including cancer. The interaction between sleep and cancer is bidirectional, with evidence suggesting that sleep disturbances may promote cancer development and vice versa.
Sleep is a nearly ubiquitous phenomenon across the phylogenetic tree, highlighting its essential role in ensuring fitness across evolutionary time. Consequently, chronic disruption of the duration, timing, or structure of sleep can cause widespread problems in multiple physiological systems, including those that regulate energy balance, immune function, and cognitive capacity, among others. Many, if not all these systems, become altered throughout the course of cancer initiation, growth, metastatic spread, treatment, and recurrence. Recent work has demonstrated how changes in sleep influence the development of chronic diseases, including cancer, in both humans and animal models. A common finding is that for some cancers (e.g., breast), chronic disruption of sleep/wake states prior to disease onset is associated with an increased risk for cancer development. Additionally, sleep disruption after cancer initiation is often associated with worse outcomes. Recently, evidence suggesting that cancer itself can affect neuronal circuits controlling sleep and wakefulness has accumulated. Patients with cancer often report difficulty falling asleep, difficulty staying asleep, and severe fatigue, during and even years after treatment. In addition to the psychological stress associated with cancer, cancer itself may alter sleep homeostasis through changes to host physiology and via currently undefined mechanisms. Moreover, cancer treatments (e.g., chemotherapy, radiation, hormonal, and surgical) may further worsen sleep problems through complex biological processes yet to be fully understood. This results in a chicken or the egg phenomenon, where it is unclear whether sleep disruption promotes cancer or cancer reciprocally disrupts sleep. This review will discuss existing evidence for both hypotheses and present a framework through which the interactions between sleep and cancer can be dissociated and causally investigated.

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