Sleep Disorders and Cancer: Difference between revisions

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== Introduction ==
== Introduction ==
There is a bidirectional correlation between cancer and sleep disorders. This means that having a sleep disorder may increase the risk of developing cancer in the future, and those with cancer are likely to experience sleep disorders during diagnosis, treatment and even ten years of survivorship. <ref name=":0">Mogavero MP, DelRosso LM, Fanfulla F, Bruni O, Ferri R. Sleep disorders and cancer: State of the art and future perspectives. Sleep Medicine Reviews. 2021 Apr 1;56:101409.</ref> <ref name=":1">Büttner-Teleagă A, Kim YT, Osel T, Richter K. [https://www.mdpi.com/1660-4601/18/21/11696 Sleep disorders in cancer—a systematic review]. International journal of environmental research and public health. 2021 Nov 7;18(21):11696.</ref> On this page, this correlation will be detailed for various sleep and cancer diseases. Underlying causes as well as preventive and curative treatment methods will also be included since sleep disorders decrease the quality of life by affecting the physical and mental health of people with cancer/tumors <ref name=":0" /> <ref name=":1" />.  
There is a bidirectional correlation between [[Oncology|cancer]] and [[Sleep Deprivation and Sleep Disorders|sleep disorders]]. This means that having a sleep disorder may increase the risk of developing cancer in the future, and those with cancer are likely to experience sleep disorders during diagnosis, treatment and even ten years of survivorship. <ref name=":0">Mogavero MP, DelRosso LM, Fanfulla F, Bruni O, Ferri R. Sleep disorders and cancer: State of the art and future perspectives. Sleep Medicine Reviews. 2021 Apr 1;56:101409.</ref> <ref name=":1">Büttner-Teleagă A, Kim YT, Osel T, Richter K. [https://www.mdpi.com/1660-4601/18/21/11696 Sleep disorders in cancer—a systematic review]. International journal of environmental research and public health. 2021 Nov 7;18(21):11696.</ref> On this page, this correlation will be detailed for various sleep and cancer diseases. Underlying causes as well as preventive and curative treatment methods will also be included since sleep disorders decrease the [[Quality of Life|quality of life]] by affecting the physical and [[Mental Health|mental health]] of people with cancer/tumors <ref name=":0" /> <ref name=":1" />.  


== Underlying Mechanism ==
== Underlying Mechanism ==
Sleep disorders in people with cancer are associated with the following: <ref>Walker WH, Borniger JC. [https://www.mdpi.com/1422-0067/20/11/2780 Molecular mechanisms of cancer-induced sleep disruption]. International journal of molecular sciences. 2019 Jun 6;20(11):2780.</ref>
Sleep disorders in people with cancer are associated with the following: <ref>Walker WH, Borniger JC. [https://www.mdpi.com/1422-0067/20/11/2780 Molecular mechanisms of cancer-induced sleep disruption]. International journal of molecular sciences. 2019 Jun 6;20(11):2780.</ref>


* '''Activation of the inflammatory response (even during chemotherapy)''': Cytokines activate microglia, thus astrocyte neurotoxic reaction.
* '''Activation of the inflammatory response (even during [[Chemotherapy Side Effects and Syndromes|chemotherapy]])''': [[Cytokines]] activate microglia, thus astrocyte neurotoxic reaction.
* '''Production of interleukins by tumours''': Interleukin-1 beta (IL-1 β) inhibits REM (rapid eye movement) sleep and affects the neurotransmitters involved in sleep (adenosine, prostaglandins, nitric oxide, GABA). Interleukin-6 (IL-6) produced in high quantities in [[Breast Cancer|breast]], [[Lung Cancer|lung]], liver and [[Prostate Cancer|prostate]] cancer also seems to reduce REM sleep and increase slow-wave sleep.
* '''Production of interleukins by tumours''': Interleukin-1 beta (IL-1 β) inhibits REM (rapid eye movement) sleep and affects the [[neurotransmitters]] involved in sleep (adenosine, prostaglandins, nitric oxide, [[GABA]]). Interleukin-6 (IL-6) produced in high quantities in [[Breast Cancer|breast]], [[Lung Cancer|lung]], liver and [[Prostate Cancer|prostate]] cancer also seems to reduce REM sleep and increase slow-wave sleep.
* '''The factors activating the hypothalamic orexin (also called hypocretin) neurons''': Ghrelin (correlated with an increase in tumour), leptin (produced in [[Breast Cancer|breast]], [[Prostate Cancer|prostate]], pancreas, ovary, [[Lung Cancer|lung]] and [[Colorectal Cancer|colorectal]] cancer and involved in the proliferation of cancer cells), a reduction in pH, [[hypoglycemia]] and some amino acids.
* '''The factors activating the hypothalamic orexin (also called hypocretin) neurons''': Ghrelin (correlated with an increase in tumour), leptin (produced in breast, prostate, pancreas, ovary, lung and [[Colorectal Cancer|colorectal]] cancer and involved in the proliferation of cancer cells), a reduction in pH, [[hypoglycemia]] and some amino acids.
* '''Changes in the serotonergic, dopaminergic, GABAergic and noradrenergic circuits induced by tumours'''
* '''Changes in the serotonergic, dopaminergic, GABAergic and noradrenergic circuits induced by tumours'''


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* '''Increase in oxidative stress and inflammatory mechanisms''':  It triggers cellular degeneration processes in cascade. <ref>Koyanagi I, Akers KG, Vergara P, Srinivasan S, Sakurai T, Sakaguchi M. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263001/ Memory consolidation during sleep and adult hippocampal neurogenesis]. Neural regeneration research. 2019 Jan;14(1):20.</ref>
* '''Increase in oxidative stress and inflammatory mechanisms''':  It triggers cellular degeneration processes in cascade. <ref>Koyanagi I, Akers KG, Vergara P, Srinivasan S, Sakurai T, Sakaguchi M. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263001/ Memory consolidation during sleep and adult hippocampal neurogenesis]. Neural regeneration research. 2019 Jan;14(1):20.</ref>
* '''Increase in tau protein''': The accumulation of this protein induces neurodegeneration <ref>Holth JK, Fritschi SK, Wang C, Pedersen NP, Cirrito JR, Mahan TE, Finn MB, Manis M, Geerling JC, Fuller PM, Lucey BP. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410369/ The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans]. Science. 2019 Feb 22;363(6429):880-4.</ref> and a bidirectional correlation between neurodegeneration and cancer exists <ref>Houck AL, Seddighi S, Driver JA. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519136/ At the crossroads between neurodegeneration and cancer: a review of overlapping biology and its implications]. Current aging science. 2018 May 1;11(2):77-89.</ref>.  
* '''Increase in [[Tauopathy|tau]] protein''': The accumulation of this protein induces [[Neurodegenerative Disease|neurodegeneration]] <ref>Holth JK, Fritschi SK, Wang C, Pedersen NP, Cirrito JR, Mahan TE, Finn MB, Manis M, Geerling JC, Fuller PM, Lucey BP. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410369/ The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans]. Science. 2019 Feb 22;363(6429):880-4.</ref> and a bidirectional correlation between neurodegeneration and cancer exists <ref>Houck AL, Seddighi S, Driver JA. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519136/ At the crossroads between neurodegeneration and cancer: a review of overlapping biology and its implications]. Current aging science. 2018 May 1;11(2):77-89.</ref>.  


== Sleep Disorders As a Risk Factor in Cancer ==
== Sleep Disorders As a Risk Factor in Cancer ==
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|-
|-
|Circadian Rhythm Disorders
|Circadian Rhythm Disorders
|Gastrointestinal and [[Breast Cancer|breast]] cancer, squamous cell carcinoma, [[Thyroid Cancer|thyroid]] and [[Prostate Cancer|prostate]] cancer (although, the evidence for it is questionable), [[Lymphoma|lymphomas]] and chronic myeloid [[Leukemia|leukaemia]]
|Gastrointestinal and breast cancer, squamous cell carcinoma, [[Thyroid Cancer|thyroid]] and prostate cancer (although, the evidence for it is questionable), [[Lymphoma|lymphomas]] and chronic myeloid [[Leukemia|leukaemia]]
|-
|-
|Insomnia
|Insomnia
|Greater risk of [[Breast Cancer|breast]], nose, trachea, liver, oral cavity, colon, [[Thyroid Cancer|thyroid]], [[Prostate Cancer|prostate]], bladder, [[Renal Cancer|kidney]] and lymphatic tumours; to a lesser extent, multiple myeloma and cervical cancer.  
|Greater risk of breast, nose, trachea, liver, oral cavity, colon, [[Thyroid Cancer|thyroid]], prostate, bladder, [[Renal Cancer|kidney]] and lymphatic tumours; to a lesser extent, multiple myeloma and cervical cancer.  
|-
|-
|[[Narcolepsy]]
|[[Narcolepsy]]
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|-
|-
|Obstructive [[Sleep Apnea]]
|Obstructive [[Sleep Apnea]]
|Greater risk of melanoma and [[Breast Cancer|breast]], uterus, [[Renal Cancer|kidney]], pancreas, [[Colorectal Cancer|colorectal]], central nervous system (but not medullary) cancer and, to a lesser extent, bladder cancer.  
|Greater risk of melanoma and breast, uterus, [[Renal Cancer|kidney]], pancreas, colorectal, central nervous system (but not medullary) cancer and, to a lesser extent, bladder cancer.  
|-
|-
|Parasomnias
|Parasomnias
|[[Breast Cancer|Breast]] and oral cavity cancer.  
|Breast and oral cavity cancer.  
|}
|}


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!'''Sleep Disorders'''
!'''Sleep Disorders'''
|-
|-
|Brain (craniopharyngioma), [[Breast Cancer|breast]] and [[Lung Cancer|lung]] cancer.  
|Brain (craniopharyngioma), breast and lung cancer.  
|Circadian Rhythm Disorders
|Circadian Rhythm Disorders
|-
|-
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A review study <ref name=":0" /> summarised the treatment options for sleep disorders in oncology rehabilitation as follows:
A review study <ref name=":0" /> summarised the treatment options for sleep disorders in oncology rehabilitation as follows:


* Melatonin <ref>Talib WH. [https://www.mdpi.com/1420-3049/23/3/518 Melatonin and cancer hallmarks]. Molecules. 2018 Feb 26;23(3):518.</ref><ref>Farhood B, Goradel NH, Mortezaee K, Khanlarkhani N, Najafi M, Sahebkar A. Melatonin and cancer: From the promotion of genomic stability to use in cancer treatment. Journal of cellular physiology. 2019 May;234(5):5613-27.</ref><ref>Mortezaee K, Najafi M, Farhood B, Ahmadi A, Potes Y, Shabeeb D, Musa AE. [https://www.sciencedirect.com/science/article/abs/pii/S0024320519303479 Modulation of apoptosis by melatonin for improving cancer treatment efficiency: An updated review]. Life sciences. 2019 Jul 1;228:228-41.</ref><ref>Li Y, Li S, Zhou Y, Meng X, Zhang JJ, Xu DP, Li HB. Melatonin for the prevention and treatment of cancer. Oncotarget 8 (24): 39896–39921.</ref>
* [[Melatonin]] <ref>Talib WH. [https://www.mdpi.com/1420-3049/23/3/518 Melatonin and cancer hallmarks]. Molecules. 2018 Feb 26;23(3):518.</ref><ref>Farhood B, Goradel NH, Mortezaee K, Khanlarkhani N, Najafi M, Sahebkar A. Melatonin and cancer: From the promotion of genomic stability to use in cancer treatment. Journal of cellular physiology. 2019 May;234(5):5613-27.</ref><ref>Mortezaee K, Najafi M, Farhood B, Ahmadi A, Potes Y, Shabeeb D, Musa AE. [https://www.sciencedirect.com/science/article/abs/pii/S0024320519303479 Modulation of apoptosis by melatonin for improving cancer treatment efficiency: An updated review]. Life sciences. 2019 Jul 1;228:228-41.</ref><ref>Li Y, Li S, Zhou Y, Meng X, Zhang JJ, Xu DP, Li HB. Melatonin for the prevention and treatment of cancer. Oncotarget 8 (24): 39896–39921.</ref>
* [[Cognitive Behavioural Therapy]] <ref>Aricò D, Raggi A, Ferri R. [https://www.frontiersin.org/articles/10.3389/fpsyg.2016.01162/full Cognitive behavioral therapy for insomnia in breast cancer survivors: a review of the literature]. Frontiers in psychology. 2016 Aug 3;7:1162.</ref><ref>Irwin MR. [https://academic.oup.com/jnci/article/110/8/799/4881761 Innovation in the treatment of insomnia in breast cancer survivors]. JNCI: Journal of the National Cancer Institute. 2018 Aug 1;110(8):799-800.</ref>
* [[Cognitive Behavioural Therapy]] <ref>Aricò D, Raggi A, Ferri R. [https://www.frontiersin.org/articles/10.3389/fpsyg.2016.01162/full Cognitive behavioral therapy for insomnia in breast cancer survivors: a review of the literature]. Frontiers in psychology. 2016 Aug 3;7:1162.</ref><ref>Irwin MR. [https://academic.oup.com/jnci/article/110/8/799/4881761 Innovation in the treatment of insomnia in breast cancer survivors]. JNCI: Journal of the National Cancer Institute. 2018 Aug 1;110(8):799-800.</ref>
* Antidepressants/ GABAergic drugs <ref>Tanimukai H, Murai T, Okazaki N, Matsuda Y, Okamoto Y, Kabeshita Y, Ohno Y, Tsuneto S. An observational study of insomnia and nightmare treated with trazodone in patients with advanced cancer. American Journal of Hospice and Palliative Medicine®. 2013 Jun;30(4):359-62.</ref><ref>Avan R, Janbabaei G, Hendouei N, Alipour A, Borhani S, Tabrizi N, Salehifar E. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040148/ The effect of pregabalin and duloxetine treatment on quality of life of breast cancer patients with taxane-induced sensory neuropathy: a randomized clinical trial]. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences. 2018;23.</ref>
* Antidepressants/ GABAergic drugs <ref>Tanimukai H, Murai T, Okazaki N, Matsuda Y, Okamoto Y, Kabeshita Y, Ohno Y, Tsuneto S. An observational study of insomnia and nightmare treated with trazodone in patients with advanced cancer. American Journal of Hospice and Palliative Medicine®. 2013 Jun;30(4):359-62.</ref><ref>Avan R, Janbabaei G, Hendouei N, Alipour A, Borhani S, Tabrizi N, Salehifar E. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040148/ The effect of pregabalin and duloxetine treatment on quality of life of breast cancer patients with taxane-induced sensory neuropathy: a randomized clinical trial]. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences. 2018;23.</ref>

Revision as of 07:57, 10 November 2023

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Introduction[edit | edit source]

There is a bidirectional correlation between cancer and sleep disorders. This means that having a sleep disorder may increase the risk of developing cancer in the future, and those with cancer are likely to experience sleep disorders during diagnosis, treatment and even ten years of survivorship. [1] [2] On this page, this correlation will be detailed for various sleep and cancer diseases. Underlying causes as well as preventive and curative treatment methods will also be included since sleep disorders decrease the quality of life by affecting the physical and mental health of people with cancer/tumors [1] [2].

Underlying Mechanism[edit | edit source]

Sleep disorders in people with cancer are associated with the following: [3]

  • Activation of the inflammatory response (even during chemotherapy): Cytokines activate microglia, thus astrocyte neurotoxic reaction.
  • Production of interleukins by tumours: Interleukin-1 beta (IL-1 β) inhibits REM (rapid eye movement) sleep and affects the neurotransmitters involved in sleep (adenosine, prostaglandins, nitric oxide, GABA). Interleukin-6 (IL-6) produced in high quantities in breast, lung, liver and prostate cancer also seems to reduce REM sleep and increase slow-wave sleep.
  • The factors activating the hypothalamic orexin (also called hypocretin) neurons: Ghrelin (correlated with an increase in tumour), leptin (produced in breast, prostate, pancreas, ovary, lung and colorectal cancer and involved in the proliferation of cancer cells), a reduction in pH, hypoglycemia and some amino acids.
  • Changes in the serotonergic, dopaminergic, GABAergic and noradrenergic circuits induced by tumours


Sleep disorders as a risk factor for developing cancer can be explained with the reasons below:

  • Increase in oxidative stress and inflammatory mechanisms:  It triggers cellular degeneration processes in cascade. [4]
  • Increase in tau protein: The accumulation of this protein induces neurodegeneration [5] and a bidirectional correlation between neurodegeneration and cancer exists [6].

Sleep Disorders As a Risk Factor in Cancer[edit | edit source]

The table below summarises the types of sleep disorders and related cancers revealed by different studies. [1]

Table 1: Sleep disorder types and their associated cancer types
Sleep Disorders Risk Factor For
Circadian Rhythm Disorders Gastrointestinal and breast cancer, squamous cell carcinoma, thyroid and prostate cancer (although, the evidence for it is questionable), lymphomas and chronic myeloid leukaemia
Insomnia Greater risk of breast, nose, trachea, liver, oral cavity, colon, thyroid, prostate, bladder, kidney and lymphatic tumours; to a lesser extent, multiple myeloma and cervical cancer.
Narcolepsy Head-neck and gastric cancer
Obstructive Sleep Apnea Greater risk of melanoma and breast, uterus, kidney, pancreas, colorectal, central nervous system (but not medullary) cancer and, to a lesser extent, bladder cancer.
Parasomnias Breast and oral cavity cancer.

Cancer Induced Sleep Disorders[edit | edit source]

According to the literature, 30-50% of individuals diagnosed with cancer are reported to experience sleep disorders. [7]

The factors affecting the sleep of people with cancer include stress, mental disorders (such as depression and anxiety), pain and treatment side effects (see the page on chemotherapy side effects and syndrome). [2]

The table below summarises reported sleep problems in different cancer types. [1]

Table 2: Cancer types and their reported sleep disorders
Cancer Diseases Sleep Disorders
Brain (craniopharyngioma), breast and lung cancer. Circadian Rhythm Disorders
All types of tumours, especially of the head, neck, breast and lung. Insomnia
Brain tumours Hypersomnia (including Narcolepsy)
Melanoma and head-neck and lung cancers. Obstructive Sleep Apnea
Gastrointestinal and renal tumours. REM Sleep Behavior Disorder (a type of parasomnia)
Hematological malignancies (multiple myeloma and polycythemia) Restless Legs Syndrome
Breast cancer Periodic Leg Movements During Sleep

Treatment Options[edit | edit source]

A review study [1] summarised the treatment options for sleep disorders in oncology rehabilitation as follows:

Interventions[edit | edit source]

A meta-analysis [24] on exercise intervention for sleep problems in cancer patients concluded that engaging in regular aerobic exercise, regardless of different durations and weekly volumes, has the potential to enhance the quality of sleep among individuals.

A randomised controlled study [25] showed that music therapy effectively reduced pain and anxiety and improved sleep quality in lung cancer patients undergoing platinum-based chemotherapy.

Resources[edit | edit source]

A booklet for the patients by American Cancer Society

References[edit | edit source]

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Mogavero MP, DelRosso LM, Fanfulla F, Bruni O, Ferri R. Sleep disorders and cancer: State of the art and future perspectives. Sleep Medicine Reviews. 2021 Apr 1;56:101409.
  2. ↑ 2.0 2.1 2.2 Büttner-Teleagă A, Kim YT, Osel T, Richter K. Sleep disorders in cancer—a systematic review. International journal of environmental research and public health. 2021 Nov 7;18(21):11696.
  3. ↑ Walker WH, Borniger JC. Molecular mechanisms of cancer-induced sleep disruption. International journal of molecular sciences. 2019 Jun 6;20(11):2780.
  4. ↑ Koyanagi I, Akers KG, Vergara P, Srinivasan S, Sakurai T, Sakaguchi M. Memory consolidation during sleep and adult hippocampal neurogenesis. Neural regeneration research. 2019 Jan;14(1):20.
  5. ↑ Holth JK, Fritschi SK, Wang C, Pedersen NP, Cirrito JR, Mahan TE, Finn MB, Manis M, Geerling JC, Fuller PM, Lucey BP. The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans. Science. 2019 Feb 22;363(6429):880-4.
  6. ↑ Houck AL, Seddighi S, Driver JA. At the crossroads between neurodegeneration and cancer: a review of overlapping biology and its implications. Current aging science. 2018 May 1;11(2):77-89.
  7. ↑ Strik H, Cassel W, Teepker M, Schulte T, Riera-Knorrenschild J, Koehler U, Seifart U. Why Do Our Cancer Patients Sleep so badly? Sleep Disorders in cancer patients: A frequent symptom with multiple causes. Oncology Research and Treatment. 2021 Jul 20;44(9):469-75.
  8. ↑ Talib WH. Melatonin and cancer hallmarks. Molecules. 2018 Feb 26;23(3):518.
  9. ↑ Farhood B, Goradel NH, Mortezaee K, Khanlarkhani N, Najafi M, Sahebkar A. Melatonin and cancer: From the promotion of genomic stability to use in cancer treatment. Journal of cellular physiology. 2019 May;234(5):5613-27.
  10. ↑ Mortezaee K, Najafi M, Farhood B, Ahmadi A, Potes Y, Shabeeb D, Musa AE. Modulation of apoptosis by melatonin for improving cancer treatment efficiency: An updated review. Life sciences. 2019 Jul 1;228:228-41.
  11. ↑ Li Y, Li S, Zhou Y, Meng X, Zhang JJ, Xu DP, Li HB. Melatonin for the prevention and treatment of cancer. Oncotarget 8 (24): 39896–39921.
  12. ↑ Aricò D, Raggi A, Ferri R. Cognitive behavioral therapy for insomnia in breast cancer survivors: a review of the literature. Frontiers in psychology. 2016 Aug 3;7:1162.
  13. ↑ Irwin MR. Innovation in the treatment of insomnia in breast cancer survivors. JNCI: Journal of the National Cancer Institute. 2018 Aug 1;110(8):799-800.
  14. ↑ Tanimukai H, Murai T, Okazaki N, Matsuda Y, Okamoto Y, Kabeshita Y, Ohno Y, Tsuneto S. An observational study of insomnia and nightmare treated with trazodone in patients with advanced cancer. American Journal of Hospice and Palliative Medicine®. 2013 Jun;30(4):359-62.
  15. ↑ Avan R, Janbabaei G, Hendouei N, Alipour A, Borhani S, Tabrizi N, Salehifar E. The effect of pregabalin and duloxetine treatment on quality of life of breast cancer patients with taxane-induced sensory neuropathy: a randomized clinical trial. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences. 2018;23.
  16. ↑ Gharib SA, Seiger AN, Hayes AL, Mehra R, Patel SR. Treatment of obstructive sleep apnea alters cancer-associated transcriptional signatures in circulating leukocytes. Sleep. 2014 Apr 1;37(4):709-14.
  17. ↑ Xie X, Pan L, Ren D, Du C, Guo Y. Effects of continuous positive airway pressure therapy on systemic inflammation in obstructive sleep apnea: a meta-analysis. Sleep medicine. 2013 Nov 1;14(11):1139-50.
  18. ↑ Baessler A, Nadeem R, Harvey M, Madbouly E, Younus A, Sajid H, Naseem J, Asif A, Bawaadam H. Treatment for sleep apnea by continuous positive airway pressure improves levels of inflammatory markers-a meta-analysis. Journal of inflammation. 2013 Dec;10(1):1-0.
  19. ↑ Lin CC, Liaw SF, Chiu CH, Chen WJ, Lin MW, Chang FT. Effects of nasal CPAP on exhaled SIRT1 and tumor necrosis factor-α in patients with obstructive sleep apnea. Respiratory physiology & neurobiology. 2016 Jul 1;228:39-46.
  20. ↑ Graybill NL, Weissig V. A review of orexin’s unprecedented potential as a novel, highly-specific treatment for various localized and metastatic cancers. SAGE open medicine. 2017 Nov 1;5:2050312117735774.
  21. ↑ Couvineau A, Dayot S, Nicole P, Gratio V, Rebours V, Couvelard A, Voisin T. The anti-tumoral properties of orexin/hypocretin hypothalamic neuropeptides: an unexpected therapeutic role. Frontiers in endocrinology. 2018 Sep 27;9:573.
  22. ↑ Xu TR, Yang Y, Ward R, Gao L, Liu Y. Orexin receptors: multi-functional therapeutic targets for sleeping disorders, eating disorders, drug addiction, cancers and other physiological disorders. Cellular signalling. 2013 Dec 1;25(12):2413-23.
  23. ↑ Ozturk N, Ozturk D, Halil Kavakli I, Okyar A. Molecular aspects of circadian pharmacology and relevance for cancer chronotherapy. International journal of molecular sciences. 2017 Oct 17;18(10):2168.
  24. ↑ Fang YY, Hung CT, Chan JC, Huang SM, Lee YH. Meta‐analysis: Exercise intervention for sleep problems in cancer patients. European journal of cancer care. 2019 Sep;28(5):e13131.
  25. ↑ Tang H, Chen L, Wang Y, Zhang Y, Yang N, Yang N. The efficacy of music therapy to relieve pain, anxiety, and promote sleep quality, in patients with small cell lung cancer receiving platinum-based chemotherapy. Supportive Care in Cancer. 2021 Dec;29(12):7299-306.
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