A multidisciplinary perspective on the complex interactions between sleep, circadian, and metabolic disruption in cancer patients

Abstract

Sleep is a basic need that is frequently set aside in modern societies. This leads to profound but complex physiological maladaptations in the body commonly referred to as circadian disruption, which recently has been characterized as a carcinogenic factor and reason for poor treatment outcomes, shortened survival, and reduced quality of life in cancer patients. As sleep and circadian physiology in cancer patients spans several disciplines including nursing science, neurology, oncology, molecular biology and medical technology, there is a lack of comprehensive and integrated approaches to deal with this serious and growing issue and at best a fractionated understanding of only part of the problem among researchers within each of these segments. Here, we take a multidisciplinary approach to comprehensively review the diagnosis and impact of sleep and circadian disruption in cancer patients. We discuss recent discoveries on molecular regulation of the circadian clock in healthy and malignant cells, the neurological and endocrine pathways controlling sleep and circadian rhythmicity, and their inputs to and outputs from the organism. The benefits and drawbacks of the various technologies, devices, and instruments used to assess sleep and circadian function, as well as the known consequences of sleep disruption and how sleep can be corrected in cancer patients, will be analyzed. We will throughout the review highlight the extensive crosstalk between sleep, circadian rhythms, and metabolic pathways involved in malignancy and identify current knowledge gaps and barriers for addressing the issue of sleep and circadian disruption in cancer patients. By addressing these issues, we hope to provide a foundation for further research as well as better and more effective care for the patients in the future.

Opposing inflammatory biomarker responses to sleep disruption in cancer patients before and during oncological therapy

“…Furthermore, both the oncology infrastructure at the study site and differences in the motivation and workload among patient-recruiting nurses within different specialities may also play a role in determining the distribution of patients across different diagnoses in this study. Other studies looking at sleep disruption in cancer patients and correlating this to effects of treatments have similar cohort sizes to that of the present study (Innominato et al, 2012;Jensen et al, 2021), but are focusing on more defined patient populations. Innominato et al (2012), for example, studied circadian disruption using Actigraph accelerometers worn on the wrist for 3 days and found that sleep disruption in 77 patients with metastatic colorectal cancer undergoing medical treatment with 5-FU, Oxaliplatin and/or Leucovorin had significantly shortened survival compared to those with non-disrupted sleep (Innominato et al, 2012).…”

“…While this is a somewhat crude assessment of sleep disruption, these guidelines represent the first attempt to include this important issue in routine cancer care. Within clinical research, however, numerous questionnaires and other instruments have been developed to investigate sleep disruption in cancer patients [recently reviewed by Jensen et al (2021) ]. The most commonly used is the extensive 19-item Pittsburgh Sleep Quality Index ( Divani et al, 2022 ), which however is time-consuming to both fill and analyze.…”

“…On the other hand, sleep disruption is also linked to augmented inflammatory processes through their cytokine- and chemokine-mediated control mechanisms ( Irwin et al, 2013 ; Wright et al, 2015 ). As such, pro-inflammatory cytokines are often found at elevated levels in both cancer patients and people suffering from poor sleep [reviewed in Jensen et al (2021) ], and are associated with nausea, depression and a generalized feeling of illness ( Vgontzas et al, 2007 ; Kapsimalis et al, 2008 ; Vumma et al, 2017 ). In addition to inflammatory cytokines and chemokines, C-reactive protein (CRP) is a commonly used biomarker of inflammation ( Sproston and Ashworth, 2018 ).…”

B serum proteome profiles revealed dysregulated proteins and mechanisms associated with insomnia patients: A preliminary study

“…MMP9 (matrix metallopeptidase 9) is involved in the proteolytic modification of ECM proteins, which affects neuronal plasticity and the synaptic properties of neurons ( Hayashi et al, 2013 ). In addition, melatonin has also a regulatory effect on the MMP9 pathway and ECM remodeling ( Jensen et al, 2021 ). These results further confirmed a link between the immune-inflammatory response and insomnia.…”

Holistic Needs Assessment of Cancer Survivors—Supporting the Process Through Digital Monitoring of Circadian Physiology

“… 41 Circadian disruption could also account for digestive complaints, 101 sleep troubles, 102 and altered metabolism. 103 Thus, the accurate evaluation of circadian function through remote monitoring of cancer patients 83 could represent a biomarker of physiological and behavioral alteration, 75 a surrogate of symptom burden and of subjective complaints, 100 , 104 , 105 as well as a potential novel target of intervention, both pharmacological and behavioral. 79 …”