Skip to main content

Advertisement

Log in

The biology of cancer-related fatigue: a review of the literature

  • Review Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

An Erratum to this article was published on 17 June 2015

Abstract

Purpose

Understanding the etiology of cancer-related fatigue (CRF) is critical to identify targets to develop therapies to reduce CRF burden. The goal of this systematic review was to expand on the initial work by the National Cancer Institute CRF Working Group to understand the state of the science related to the biology of CRF and, specifically, to evaluate studies that examined the relationships between biomarkers and CRF and to develop an etiologic model of CRF to guide researchers on pathways to explore or therapeutic targets to investigate.

Methods

This review was completed by the Multinational Association of Supportive Care in Cancer Fatigue Study Group–Biomarker Working Group. The initial search used three terms (biomarkers, fatigue, cancer), which yielded 11,129 articles. After removing duplicates, 9145 articles remained. Titles were assessed for the keywords “cancer” and “fatigue” resulting in 3811 articles. Articles published before 2010 and those with samples <50 were excluded, leaving 75 articles for full-text review. Of the 75 articles, 28 were further excluded for not investigating the associations of biomarkers and CRF.

Results

Of the 47 articles reviewed, 25 were cross-sectional and 22 were longitudinal studies. More than half (about 70 %) were published recently (2010–2013). Almost half (45 %) enrolled breast cancer participants. The majority of studies assessed fatigue using self-report questionnaires, and only two studies used clinical parameters to measure fatigue.

Conclusions

The findings from this review suggest that CRF is linked to immune/inflammatory, metabolic, neuroendocrine, and genetic biomarkers. We also identified gaps in knowledge and made recommendations for future research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Barsevick AM, Irwin MR, Hinds P et al (2013) Recommendations for high-priority research on cancer-related fatigue in children and adults. J Natl Cancer Inst 105:1432–1440. doi:10.1093/jnci/djt242

    Article  PubMed Central  PubMed  Google Scholar 

  2. Mustian KM, Peppone LJ, Palesh OG, Janelsins MC, Mohile SG, Purnell JQ, Darling TV (2009) Exercise and cancer-related fatigue. U S Oncol 5:20–23

    Google Scholar 

  3. Mustian KM, Sprod LK, Janelsins M, Peppone LJ, Mohile S (2012) Exercise recommendations for cancer-related fatigue, cognitive impairment, sleep problems, depression, pain, anxiety, and physical dysfunction: a review. Oncol Hematol Rev 8:81–88

    PubMed Central  PubMed  Google Scholar 

  4. Berger AM, Gerber LH, Mayer DK (2012) Cancer-related fatigue: implications for breast cancer survivors. Cancer 15:2261–2269. doi:10.1002/cncr.27475

    Article  Google Scholar 

  5. Campos MP, Hassan BJ, Riechelmann R, Del Giglio A (2011) Cancer-related fatigue: a practical review. Ann Oncol 22:1273–1279. doi:10.1093/annonc/mdq458

    Article  CAS  PubMed  Google Scholar 

  6. Ryan JL, Carroll JK, Ryan EP, Mustian KM, Fiscella K, Morrow GR (2007) Mechanisms of cancer-related fatigue. Oncologist 12:22–34

    Article  CAS  PubMed  Google Scholar 

  7. Wang XS, Woodruff JF (2014) Cancer-related and treatment-related fatigue. Gynecol Oncol. doi:10.1016/j.ygyno.2014.10.013

    PubMed Central  Google Scholar 

  8. Howell D, Keller-Olaman S, Oliver TK, Hack T, Broadfield L, Biggs K, Chung J, Esplen MJ, Gravelle D, Green E, Hamel M, Harth T, Johnston P, McLeod D, Swinton N, Syme A, Olson K, on behalf of the Cancer Journey Advisory Group of the Canadian Partnership Against Cancer (2011) A pan-Canadian practice guideline: screening, assessment and care of cancer-related fatigue in adults with cancer. Canadian Partnership Against Cancer (Cancer Journey Advisory Group) and the Canadian Association of Psychosocial Oncology, Toronto

    Google Scholar 

  9. Bower JE, Bak K, Berger A, Breitbart W, Escalante CP, Ganz PA, Schnipper HH, Lacchetti C, Ligibel JA, Lyman GH, Ogaily MS, Pirl WF, Jacobsen PB, American Society of Clinical Oncology (2014) Screening, assessment, and management of fatigue in adult survivors of cancer: an American Society of Clinical oncology clinical practice guideline adaptation. J Clin Oncol 32:1840–1850. doi:10.1200/JCO.2013.53.4495

    Article  PubMed Central  PubMed  Google Scholar 

  10. Mitchell SA, Hoffman AJ, Clark JC, DeGennaro RM, Poirier P, Robinson CB, Weisbrod BL (2014) Putting evidence into practice: an update of evidence-based interventions for cancer-related fatigue during and following treatment. Clin J Oncol Nurs 18(Suppl):38–58. doi:10.1188/14.CJON.S3.38-58

    Article  PubMed  Google Scholar 

  11. National Comprehensive Cancer Network (NCCN) Guidelines Version 2.2015 Panel Members Cancer-Related Fatigue (2015) NCCN clinical practice guidelines in oncology: cancer-related fatigue. www.nccn.org/professionals/physician_gls/f_guidelines.asp#fatigue Accessed 27 April 2015

  12. Massacesi C, Terrazzino S, Marcucci F, Rocchi MB, Lippe P, Bisonni R, Lombardo M, Pilone A, Mattioli R, Leon A (2006) Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism predicts the risk of gastrointestinal toxicity and fatigue induced by irinotecan-based chemotherapy. Cancer 106:1007–1016. doi:10.1002/cncr.21722

    Article  CAS  PubMed  Google Scholar 

  13. Booker R, Olson K, Pilarski LM, Noon JP, Bahlis NJ (2009) The relationships among physiologic variables, quality of life, and fatigue in patients with multiple myeloma. Oncol Nurs Forum 36:209–216. doi:10.1188/09.ONF.209-216

    Article  PubMed  Google Scholar 

  14. Gerber LH, Stout N, McGarvey C, Soballe P, Shieh CY, Diao G, Springer BA, Pfalzer LA (2011) Factors predicting clinically significant fatigue in women following treatment for primary breast cancer. Support Care Cancer 19:1581–1591. doi:10.1007/s00520-010-0986-7

    Article  PubMed Central  PubMed  Google Scholar 

  15. Fernández-de-las-Pẽnas C, Fernández-Lao C, Cantarero-Villanueva I, Ambite-Quesada S, Rivas-Martínez I, del Moral-Avila R, Arroyo-Morales M (2012) Catechol-O-methyltransferase genotype (Val158met) modulates cancer-related fatigue and pain sensitivity in breast cancer survivors. Breast Cancer Res Treat 133:405–412. doi:10.1007/s10549-011-1757-y

    Article  PubMed  Google Scholar 

  16. Fernández-de-Las-Pẽnas C, Cantarero-Villanueva I, Fernández-Lao C, Ambite-Quesada S, Díaz-Rodríguez L, Rivas-Martínez I, del Moral-Avila R, Arroyo-Morales M (2012) Influence of catechol-o-methyltransferase genotype (Val158Met) on endocrine, sympathetic nervous and mucosal immune systems in breast cancer survivors. Breast 21:199–203. doi:10.1016/j.breast.2011.09.012

    Article  PubMed  Google Scholar 

  17. Weinrib AZ, Sephton SE, Degeest K, Penedo F, Bender D, Zimmerman B, Kirschbaum C, Sood AK, Lubaroff DM, Lutgendorf SK (2010) Diurnal cortisol dysregulation, functional disability, and depression in women with ovarian cancer. Cancer 116:4410–4419. doi:10.1002/cncr.25299

    Article  PubMed Central  PubMed  Google Scholar 

  18. Schrepf A, Clevenger L, Christensen D et al (2013) Cortisol and inflammatory processes in ovarian cancer patients following primary treatment: relationships with depression, fatigue, and disability. Brain Behav Immun 30(Suppl):S126–S134. doi:10.1016/j.bbi.2012.07.022

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Alexander S, Minton O, Andrews P, Stone P (2009) A comparison of the characteristics of disease-free breast cancer survivors with or without cancer-related fatigue syndrome. Eur J Cancer 45:384–392. doi:10.1016/j.ejca.2008.09.010

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Capuano G, Pavese I, Satta F, Tosti M, Palladino A, Del Grosso A, Di Palma M (2008) Correlation between anemia, unintentional weight loss and inflammatory status on cancer-related fatigue and quality of life before chemo and radiotherapy. e-SPEN Eur e-J Clin Nutr Metab 3:e147–e151. doi:10.1016/j.eclnm.2008.04.008

    Article  Google Scholar 

  21. Rausch SM, Clark MM, Patten C, Liu H, Felten S, Li Y, Sloan J, Yang P (2010) Relationship between cytokine gene single nucleotide polymorphisms and symptom burden and quality of life in lung cancer survivors. Cancer 116:4103–4113. doi:10.1002/cncr.25255

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Gélinas C, Fillion L (2004) Factors related to persistent fatigue following completion of breast cancer treatment. Oncol Nurs Forum 31:269–278. doi:10.1188/04.ONF.269-278

    Article  PubMed  Google Scholar 

  23. Pusztai L, Mendoza TR, Reuben JM et al (2004) Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy. Cytokine 25:94–102. doi:10.1016/j.cyto.2003.10.004

    Article  CAS  PubMed  Google Scholar 

  24. Meyers CA, Albitar M, Estey E (2005) Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome. Cancer 104:788–793. doi:10.1002/cncr.21234

    Article  CAS  PubMed  Google Scholar 

  25. Collado-Hidalgo A, Bower JE, Ganz PA, Cole SW, Irwin MR (2006) Inflammatory biomarkers for persistent fatigue in breast cancer survivors. Clin Cancer Res 12:2759–2766. doi:10.1158/1078-0432.CCR-05-2398

    Article  CAS  PubMed  Google Scholar 

  26. Orre IJ, Murison R, Dahl AA, Ueland T, Aukrust P, Fosså SD (2009) Levels of circulating interleukin-1 receptor antagonist and C-reactive protein in long-term survivors of testicular cancer with chronic cancer-related fatigue. Brain Behav Immun 23:868–874. doi:10.1016/j.bbi.2009.04.003

    Article  CAS  PubMed  Google Scholar 

  27. Steel JL, Kim KH, Dew MA, Unruh ML, Antoni MH, Olek MC, Geller DA, Carr BI, Butterfield LH, Gamblin TC (2010) Cancer-related symptom clusters, eosinophils, and survival in hepatobiliary cancer: an exploratory study. J Pain Symptom Manage 39:859–871. doi:10.1016/j.jpainsymman.2009.09.019

    Article  PubMed Central  PubMed  Google Scholar 

  28. Wang XS, Shi Q, Williams LA, Mao L, Cleeland CS, Komaki RR, Mobley GM, Liao Z (2010) Inflammatory cytokines are associated with the development of symptom burden in patients with NSCLC undergoing concurrent chemoradiation therapy. Brain Behav Immun 24:968–974. doi:10.1016/j.bbi.2010.03.009

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Bower JE, Ganz PA, Irwin MR, Kwan L, Breen EC, Cole SW (2011) Inflammation and behavioral symptoms after breast cancer treatment: do fatigue, depression, and sleep disturbance share a common underlying mechanism? J Clin Oncol 29:3517–3522. doi:10.1200/JCO.2011.36.1154

    Article  PubMed Central  PubMed  Google Scholar 

  30. Orre IJ, Reinertsen KV, Aukrust P, Dahl AA, Fosså SD, Ueland T, Murison R (2011) Higher levels of fatigue are associated with higher CRP levels in disease-free breast cancer survivors. J Psychosom Res 71:136–141. doi:10.1016/j.jpsychores.2011.04.003

    Article  PubMed  Google Scholar 

  31. Alfano CM, Imayama I, Neuhouser ML et al (2012) Fatigue, inflammation, and ω-3 and ω-6 fatty acid intake among breast cancer survivors. J Clin Oncol 30:1280–1287. doi:10.1200/JCO.2011.36.4109

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Clevenger L, Schrepf A, Christensen D et al (2012) Sleep disturbance, cytokines, and fatigue in women with ovarian cancer. Brain Behav Immun 26:1037–1044. doi:10.1016/j.bbi.2012.04.003

    Article  PubMed Central  PubMed  Google Scholar 

  33. de Raaf PJ, Sleijfer S, Lamers CH, Jager A, Gratama JW, van der Rijt CC (2012) Inflammation and fatigue dimensions in advanced cancer patients and cancer survivors: an explorative study. Cancer 118:6005–6011. doi:10.1002/cncr.27613

    Article  PubMed  Google Scholar 

  34. Fagundes CP, Glaser R, Alfano CM et al (2012) Fatigue and herpesvirus latency in women newly diagnosed with breast cancer. Brain Behav Immun 26:394–400. doi:10.1016/j.bbi.2011.09.014

    Article  PubMed Central  PubMed  Google Scholar 

  35. Liu L, Mills PJ, Rissling M, Fiorentino L, Natarajan L, Dimsdale JE, Sadler GR, Parker BA, Ancoli-Israel S (2012) Fatigue and sleep quality are associated with changes in inflammatory markers in breast cancer patients undergoing chemotherapy. Brain Behav Immun 26:706–713. doi:10.1016/j.bbi.2012.02.001

    Article  PubMed Central  PubMed  Google Scholar 

  36. Courtier N, Gambling T, Enright S, Barrett-Lee P, Abraham J, Mason MD (2013) Psychological and immunological characteristics of fatigued women undergoing radiotherapy for early-stage breast cancer. Support Care Cancer 21:173–181. doi:10.1007/s00520-012-1508-6

    Article  PubMed  Google Scholar 

  37. Fung FY, Li M, Breunis H, Timilshina N, Minden MD, Alibhai SM (2013) Correlation between cytokine levels and changes in fatigue and quality of life in patients with acute myeloid leukemia. Leuk Res 37:274–279. doi:10.1016/j.leukres.2012.11.013

    Article  CAS  PubMed  Google Scholar 

  38. Hamre H, Zeller B, Kanellopoulos A et al (2013) Serum cytokines and chronic fatigue in adults surviving after childhood leukemia and lymphoma. Brain Behav Immun 30:80–87. doi:10.1016/j.bbi.2013.01.006

    Article  CAS  PubMed  Google Scholar 

  39. Laird BJ, McMillan DC, Fayers P, Fearon K, Kaasa S, Fallon MT, Klepstad P (2013) The systemic inflammatory response and its relationship to pain and other symptoms in advanced cancer. Oncologist 18:1050–1055. doi:10.1634/theoncologist.2013-0120

    Article  PubMed Central  PubMed  Google Scholar 

  40. Paiva CE, Paiva BS (2013) Prevalence, predictors, and prognostic impact of fatigue among Brazilian outpatients with advanced cancers. Support Care Cancer 21:1053–1060. doi:10.1007/s00520-012-1625-2

    Article  PubMed  Google Scholar 

  41. Pertl MM, Hevey D, Boyle NT, Hughes MM, Collier S, O’Dwyer AM, Harkin A, Kennedy MJ, Connor TJ (2013) C-reactive protein predicts fatigue independently of depression in breast cancer patients prior to chemotherapy. Brain Behav Immun 34:108–119. doi:10.1016/j.bbi.2013.07.177

    Article  CAS  PubMed  Google Scholar 

  42. Meyerhardt JA, Sloan JA, Sargent DJ et al (2005) Associations between plasma insulin-like growth factor proteins and C-peptide and quality of life in patients with metastatic colorectal cancer. Cancer Epidemiol Biomarkers Prev 14:1402–1410. doi:10.1158/1055-9965.epi-04-0862

    Article  CAS  PubMed  Google Scholar 

  43. Thornton LM, Andersen BL, Blakely WP (2010) The pain, depression, and fatigue symptom cluster in advanced breast cancer: covariation with the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Health Psychol 29:333–337. doi:10.1037/a0018836

    Article  PubMed Central  PubMed  Google Scholar 

  44. Fagundes CP, Murray DM, Hwang BS, Gouin JP, Thayer JF, Sollers JJ 3rd, Shapiro CL, Malarkey WB, Kiecolt-Glaser JK (2011) Sympathetic and parasympathetic activity in cancer-related fatigue: more evidence for a physiological substrate in cancer survivors. Psychoneuroendocrinology 36:1137–1147. doi:10.1016/j.psyneuen.2011.02.005

    Article  PubMed Central  PubMed  Google Scholar 

  45. Miaskowski C, Dodd M, Lee K et al (2010) Preliminary evidence of an association between a functional interleukin-6 polymorphism and fatigue and sleep disturbance in oncology patients and their family caregivers. J Pain Symptom Manage 40:531–544. doi:10.1016/j.jpainsymman.2009.12.006

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Jim HS, Park JY, Permuth-Wey J, Rincon MA, Phillips KM, Small BJ, Jacobsen PB (2012) Genetic predictors of fatigue in prostate cancer patients treated with androgen deprivation therapy: preliminary findings. Brain Behav Immun 26:1030–1036. doi:10.1016/j.bbi.2012.03.001

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Bower JE, Ganz PA, Irwin MR, Castellon S, Arevalo J, Cole SW (2013) Cytokine genetic variations and fatigue among patients with breast cancer. J Clin Oncol 31:1656–1661. doi:10.1200/jco.2012.46.2143

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Reyes-Gibby CC, Wang J, Spitz M, Wu X, Yennurajalingam S, Shete S (2013) Genetic variations in interleukin-8 and interleukin-10 are associated with pain, depressed mood, and fatigue in lung cancer patients. J Pain Symptom Manage 46:161–172. doi:10.1016/j.jpainsymman.2012.07.019

    Article  PubMed Central  PubMed  Google Scholar 

  49. Wratten C, Kilmurray J, Nash S, Seldon M, Hamilton CS, O’Brien PC, Denham JW (2004) Fatigue during breast radiotherapy and its relationship to biological factors. Int J Radiat Oncol Biol Phys 59:160–167. doi:10.1016/j.ijrobp.2003.10.008

    Article  PubMed  Google Scholar 

  50. Rich T, Innominato PF, Boerner J, Mormont MC, Iacobelli S, Baron B, Jasmin C, Levi F (2005) Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and dampened 24-hour rest-activity patterns in patients with metastatic colorectal cancer. Clin Cancer Res 11:1757–1764. doi:10.1158/1078-0432.ccr-04-2000

    Article  CAS  PubMed  Google Scholar 

  51. Shafqat A, Einhorn LH, Hanna N, Sledge GW, Hanna A, Juliar BE, Monahan P, Bhatia S (2005) Screening studies for fatigue and laboratory correlates in cancer patients undergoing treatment. Ann Oncol 16:1545–1550. doi:10.1093/annonc/mdi267

    Article  CAS  PubMed  Google Scholar 

  52. Landmark-Hoyvik H, Reinertsen KV, Loge JH, Fossa SD, Borresen-Dale AL, Dumeaux V (2009) Alterations of gene expression in blood cells associated with chronic fatigue in breast cancer survivors. Pharmacogenomics J 9:333–340. doi:10.1038/tpj.2009.27

    Article  CAS  PubMed  Google Scholar 

  53. Reinertsen KV, Cvancarova M, Loge JH, Edvardsen H, Wist E, Fossa SD (2010) Predictors and course of chronic fatigue in long-term breast cancer survivors. J Cancer Surviv 4:405–414. doi:10.1007/s11764-010-0145-7

    Article  PubMed Central  PubMed  Google Scholar 

  54. Reinertsen KV, Grenaker Alnaes GI, Landmark-Hoyvik H, Loge JH, Wist E, Kristensen VN, Fossa SD, Edvardsen H (2011) Fatigued breast cancer survivors and gene polymorphisms in the inflammatory pathway. Brain Behav Immun 25:1376–1383. doi:10.1016/j.bbi.2011.04.001

    Article  CAS  PubMed  Google Scholar 

  55. Kurz K, Fiegl M, Holzner B, Giesinger J, Pircher M, Weiss G, Denz HA, Fuchs D (2012) Fatigue in patients with lung cancer is related with accelerated tryptophan breakdown. PLoS One 7, e36956. doi:10.1371/journal.pone.0036956

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Minton O, Strasser F, Radbruch L, Stone P (2012) Identification of factors associated with fatigue in advanced cancer: a subset analysis of the European palliative care research collaborative computerized symptom assessment data set. J Pain Symptom Manage 43:226–235. doi:10.1016/j.jpainsymman.2011.03.025

    Article  PubMed  Google Scholar 

  57. Wang XS, Williams LA, Krishnan S et al (2012) Serum sTNF-R1, IL-6, and the development of fatigue in patients with gastrointestinal cancer undergoing chemoradiation therapy. Brain Behav Immun 26:699–705. doi:10.1016/j.bbi.2011.12.007

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Kwak SM, Choi YS, Yoon HM et al (2012) The relationship between interleukin-6, tumor necrosis factor-α, and fatigue in terminally ill cancer patients. Palliat Med 26:275–282. doi:10.1177/0269216311406991

    Article  PubMed  Google Scholar 

  59. Kiecolt-Glaser JK, Bennett JM, Andridge R, Peng J, Shapiro CL, Malarkey WB, Emery CF, Layman R, Mrozek EE, Glaser R (2014) Yoga’s impact on inflammation, mood, and fatigue in breast cancer survivors: a randomized controlled trial. J Clin Oncol 32(10):1040–1049

    Article  PubMed Central  PubMed  Google Scholar 

  60. Lee YW, Cho HJ, Lee WH, Sonntag WE (2012) Whole brain radiation-induced cognitive impairment: pathophysiological mechanisms and therapeutic targets. Biomol Ther (Seoul) 20:357–370. doi:10.4062/biomolther.2012.20.4.357

    Article  CAS  Google Scholar 

  61. McDonald B, Conroy S, Ahles T, West J, Saykin A (2010) Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study. Breast Cancer Res Treat 123:819–828. doi:10.1007/s10549-010-1088-4

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Schagen SB, Muller MJ, Boogerd W, Mellenbergh GJ, van Dam FSAM (2006) Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients. J Natl Cancer Inst 98:1742–1745

    Article  CAS  PubMed  Google Scholar 

  63. Trinchieri G (2012) Cancer and inflammation: an old intuition with rapidly evolving new concepts. Annu Rev Immunol 30:677–706. doi:10.1146/annurev-immunol-020711-075008

    Article  CAS  PubMed  Google Scholar 

  64. Filler K, Lyon D, Bennett J, McCain N, Elswick R, Lukkahatai N, Saligan LN (2014) Association of mitochondrial dysfunction and fatigue: a review of literature. BBA Clin 1:12–23

    Article  PubMed Central  PubMed  Google Scholar 

  65. Christensen JF, Jones LW, Andersen JL, Daugaard G, Rorth M, Hojman P (2014) Muscle dysfunction in cancer patients. Ann Oncol 25:947–958. doi:10.1093/annonc/mdt551

    Article  CAS  PubMed  Google Scholar 

  66. Reid MB, Moylan JS (2011) Beyond atrophy: redox mechanisms of muscle dysfunction in chronic inflammatory disease. J Physiol 589:2171–2179. doi:10.1113/jphysiol.2010.203356

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Cumiskey D, Pickering M, O’Connor JJ (2007) Interleukin-18 mediated inhibition of LTP in the rat dentate gyrus is attenuated in the presence of mGluR antagonists. Neurosci Lett 412:206–210

    Article  CAS  PubMed  Google Scholar 

  68. Irwin MR, Olmstead RE, Ganz PA, Haque R (2013) Sleep disturbance, inflammation and depression risk in cancer survivors. Brain Behav Immun 30(Suppl):S58–S67. doi:10.1016/j.bbi.2012.05.002

    Article  PubMed Central  PubMed  Google Scholar 

  69. Morris G, Berk M, Galecki P, Walder K, Maes M (2015) The neuro-immune pathophysiology of central and peripheral fatigue in systemic immune-inflammatory and neuro-immune diseases. Mol Neurobiol. doi:10.1007/s12035-015-9090-9

  70. Santello M, Bezzi P, Volterra A (2011) TNFα controls glutamatergic gliotransmission in the hippocampal dentate gyrus. Neuron 69:988–1001. doi:10.1016/j.neuron.2011.02.003

    Article  CAS  PubMed  Google Scholar 

  71. Fowler JA, Mundy GR, Lwin ST, Edwards CM (2012) Bone marrow stromal cells create a permissive microenvironment for myeloma development. Cancer Res 72:2183–2189. doi:10.1158/0008-5472.CAN-11-2067

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Nefedova Y, Landowski TH, Dalton WS (2003) Bone marrow stromal-derived soluble factors and direct cell contact contribute to de novo drug resistance of myeloma cells by distinct mechanisms. Leukemia 17:1175–1182

    Article  CAS  PubMed  Google Scholar 

  73. Serhan CN (2010) Novel lipid mediators and resolution mechanisms in acute inflammation: to resolve or not? Am J Pathol 177:1576–1591. doi:10.2353/ajpath.2010.100322

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  74. Kanczkowski W, Alexaki VI, Tran N et al (2013) Hypothalamo-pituitary and immune-dependent adrenal regulation during systemic inflammation. Proc Natl Acad Sci U S A 110:14801–14806. doi:10.1073/pnas.1313945110

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  75. Monk JP, Phillips G, Waite R et al (2006) Assessment of tumour necrosis factor alpha blockade as an intervention to improve tolerability of dose-intensive chemotherapy in cancer patients. J Clin Oncol 24:1852–1859

    Article  CAS  PubMed  Google Scholar 

  76. Tookman AJ, Jones CL, DeWitte M, Lodge PJ (2008) Fatigue in patients with advanced cancer: a pilot study of an intervention with infliximab. Support Care Cancer 16:1131–1140. doi:10.1007/s00520-008-0429-x

    Article  CAS  PubMed  Google Scholar 

  77. Yennurajalingam S, Frisbee-Hume S, Palmer JL et al (2013) Reduction of cancer-related fatigue with dexamethasone: a double-blind, randomized, placebo-controlled trial in patients with advanced cancer. J Clin Oncol 31:3076–3082. doi:10.1200/JCO.2012.44.4661

    Article  CAS  PubMed  Google Scholar 

  78. Minton O, Richardson A, Sharpe M, Hotopf M, Stone P (2008) A systematic review and meta-analysis of the pharmacological treatment of cancer-related fatigue. J Natl Cancer Inst 100:1155–1166. doi:10.1093/jnci/djn250

    Article  CAS  PubMed  Google Scholar 

  79. Bower JE, Crosswell AD, Stanton AL, Crespi CM, Winston D, Arevalo J, Ma J, Cole SW, Ganz PA (2014) Mindfulness meditation for younger breast cancer survivors: a randomized controlled trial. Cancer. doi:10.1002/cncr.29194

    Google Scholar 

  80. Bower JE (2014) Cancer-related fatigue—mechanisms, risk factors, and treatments. Nat Rev Clin Oncol 11:597–609. doi:10.1038/nrclinonc.2014.127

    Article  CAS  PubMed  Google Scholar 

  81. NCCN Guidelines Version 2.2015 Panel Members Cancer- and Chemotherapy-Induced Anemia (2015) NCCN clinical practice guidelines in oncology: cancer- and chemotherapy-induced anemia. www.nccn.org/professionals/physician_gls/pdf/anemia.pdf Accessed 27 April 2015

  82. McEwen BS, Seeman T (1999) Protective and damaging effects of mediators of stress: elaborating and testing the concepts of allostasis and allostatic load. Ann N Y Acad Sci 896:30–47

    Article  CAS  PubMed  Google Scholar 

  83. Glaus A, Boehme C, Thürlimann B, Ruhstaller T, Hsu Schmitz SF, Morant R, Senn HJ, von Moos R (2006) Fatigue and menopausal symptoms in women with breast cancer undergoing hormonal cancer treatment. Ann Oncol 17:801–806. doi:10.1093/annonc/mdl030

    Article  CAS  PubMed  Google Scholar 

  84. Banthia R, Malcarne VL, Ko CM, Varni JW, Sadler GR (2009) Fatigued breast cancer survivors: the role of sleep quality, depressed mood, stage and age. Psychol Health 24:965–980. doi:10.1080/08870440802110831

    Article  PubMed  Google Scholar 

  85. Butt Z, Rao AV, Lai JS, Abernethy AP, Rosenbloom SK, Cella D (2010) Age-associated differences in fatigue among patients with cancer. J Pain Symptom Manage 40:217–223. doi:10.1016/j.jpainsymman.2009.12.016

    Article  PubMed Central  PubMed  Google Scholar 

  86. Kyrdalen AE, Dahl AA, Hernes E, Hem E, Fossa SD (2010) Fatigue in prostate cancer survivors treated with definitive radiotherapy and LHRH analogs. Prostate 70:1480–1489. doi:10.1002/pros.21183

    Article  PubMed  Google Scholar 

  87. Luctkar-Flude M, Groll D, Woodend K, Tranmer J (2009) Fatigue and physical activity in older patients with cancer: a six-month follow-up study. Oncol Nurs Forum 36:194–202. doi:10.1188/09.onf.194-202

    Article  PubMed  Google Scholar 

  88. Singer S, Kuhnt S, Zwerenz R et al (2011) Age- and sex-standardised prevalence rates of fatigue in a large hospital-based sample of cancer patients. Br J Cancer 105:445–451. doi:10.1038/bjc.2011.251

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  89. Soltow D, Given BA, Given CW (2010) Relationship between age and symptoms of pain and fatigue in adults undergoing treatment for cancer. Cancer Nurs 33:296–303. doi:10.1097/NCC.0b013e3181ce5a1a

    Article  PubMed  Google Scholar 

  90. Winters-Stone KM, Bennett JA, Nail L, Schwartz A (2008) Strength, physical activity, and age predict fatigue in older breast cancer survivors. Oncol Nurs Forum 35:815–821. doi:10.1188/08.onf.815-821

    Article  PubMed  Google Scholar 

  91. Storey DJ, McLaren DB, Atkinson MA, Butcher I, Frew LC, Smyth JF, Sharpe M (2012) Clinically relevant fatigue in men with hormone-sensitive prostate cancer on long-term androgen deprivation therapy. Ann Oncol 23:1542–1549. doi:10.1093/annonc/mdr447

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by the Multinational Association of Supportive Care in Cancer and the Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, and Grants NCI K07CA120025, UG1 CA189961 and R01 CA181064.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to Leorey N. Saligan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saligan, L.N., Olson, K., Filler, K. et al. The biology of cancer-related fatigue: a review of the literature. Support Care Cancer 23, 2461–2478 (2015). https://doi.org/10.1007/s00520-015-2763-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-015-2763-0

Keywords

Navigation