Molecular Mechanisms of Cancer-Induced Sleep Disruption

Abstract

Sleep is essential for health. Indeed, poor sleep is consistently linked to the development of systemic disease, including depression, metabolic syndrome, and cognitive impairments. Further evidence has accumulated suggesting the role of sleep in cancer initiation and progression (primarily breast cancer). Indeed, patients with cancer and cancer survivors frequently experience poor sleep, manifesting as insomnia, circadian misalignment, hypersomnia, somnolence syndrome, hot flushes, and nightmares. These problems are associated with a reduction in the patients’ quality of life and increased mortality. Due to the heterogeneity among cancers, treatment regimens, patient populations and lifestyle factors, the etiology of cancer-induced sleep disruption is largely unknown. Here, we discuss recent advances in understanding the pathways linking cancer and the brain and how this leads to altered sleep patterns. We describe a conceptual framework where tumors disrupt normal homeostatic processes, resulting in aberrant changes in physiology and behavior that are detrimental to health. Finally, we discuss how this knowledge can be leveraged to develop novel therapeutic approaches for cancer-associated sleep disruption, with special emphasis on host-tumor interactions.

Stress and Symptom Burden in Oncology Patients During the COVID-19 Pandemic

“… 25 Sleep disturbance is reported by 30%–88% of oncology patients. 26 , 27 Although findings from preclinical and clinical studies suggest that stress has a negative impact on the sleep-wake cycle, 28 , 29 no data are available on the relationship between stress and sleep disturbance in oncology patients. Similarly although increased stress can exacerbate chronic pain, 30 , 31 less is known about this relationship in patients with cancer.…”

Analysis of Changes in Cancer-Related Fatigue of Breast Cancer Patients Receiving an Integrative Medicine Program

“… 50 As reviewed in detail recently, CRF frequently occurs alongside and is interrelated with sleep disturbances and further neurophysiological symptoms, homeostatic processes under control of the master circadian clock in the subcortical brain. 51 Interventions that affect the biorhythm may therefore also influence mood and well-being, as well as might modulate fatigue symptoms.…”

Neurodevelopmental Consequences of Pediatric Cancer and Its Treatment: The Role of Sleep

“…Tumors produce IL 1-β in high quantities, which inhibits rapid-eye-movement (REM) and promotes NREM sleep and influences numerous neurotransmitters involved in sleep regulation (adenosine, prostaglandins, nitric oxide, GABA). IL-6 also seems to reduce REM sleep and increase slow-wave sleep; the same role seems to be played by TNF-α [57]. Hormones are also involved in the close connection between sleep and tumors: ghrelin, related to an increase in tumor progression and a reduction in survival, could act on orexinergic neurons by activating them; leptin, involved in the proliferation of cancer cells, can induce the production of IL-6 and TNF-α; moreover, it seems to activate hypothalamic neurons, in turn connected with orexinergic neurons.…”

“…Hormones are also involved in the close connection between sleep and tumors: ghrelin, related to an increase in tumor progression and a reduction in survival, could act on orexinergic neurons by activating them; leptin, involved in the proliferation of cancer cells, can induce the production of IL-6 and TNF-α; moreover, it seems to activate hypothalamic neurons, in turn connected with orexinergic neurons. Finally, neurons expressing calcitonin-gene-related peptide are sensitive to changes in pCO 2 and are involved in the onset of arousals and awakening [57].…”