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 of the biology of CRF. 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, 7,175 articles remained. Titles were assessed for the keywords, “cancer” and “fatigue” resulting in 3,811 articles. Articles published before 2010 and those with samples <50 were excluded, leaving 75 articles for full-text review. Of the 75 articles, 25 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. Less than half (44%) were published recently (2010-2013). Almost half (46%) enrolled breast cancer participants. A 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.

Background Although telomere shortening occurs as a natural part of aging, there is now a robust body of research that suggests that there is a relationship between psychosocial, environmental, and behavioral factors and changes in telomere length. These factors need to be considered when integrating telomere measurement in biobehavioral research studies. Objectives This article provides a brief summary of the known facts about telomere biology and an integrative review of current human research studies that assessed relationships between psychosocial, environmental, or behavioral factors and telomere length. Methods An integrative review was conducted to examine human research studies that focused on psychosocial, environmental, and behavioral factors affecting telomere length and telomerase activity using the electronic databases PubMed/Medline and CINAHL from 2003 to the present. In addition to the known individual factors that are associated with telomere length, the results of the integrative review suggest that perceived stress, childhood adversities, major depressive disorder, educational attainment, physical activity, and sleep duration should also be measured. Discussion Multiple factors have been shown to affect telomere length. To advance understanding of the role of telomere length in health and disease risk, it will be important to further elucidate the mechanisms that contribute to telomere shortening.

Fatigue is often described by patients as a lack of energy, mental or physical tiredness, diminished endurance, and prolonged recovery after physical activity. Etiologic mechanisms underlying fatigue are not well understood; however, fatigue is a hallmark symptom of mitochondrial disease, making mitochondrial dysfunction a putative biological mechanism for fatigue. Therefore, this review examined studies that investigated the association of markers of mitochondrial dysfunction with fatigue and proposes possible research directions to enhance understanding of the role of mitochondrial dysfunction in fatigue. A thorough search using PubMed, Scopus, Web of Science, and Embase databases returned 1,220 articles. After application of inclusion and exclusion criteria, a total of 25 articles meeting eligibility criteria were selected for full review. Dysfunctions in the mitochondrial structure, mitochondrial function (mitochondrial enzymes and oxidative/nitrosative stress), mitochondrial energy metabolism (ATP production and fatty acid metabolism), immune response, and genetics were investigated as potential contributors to fatigue. Carnitine was the most investigated mitochondrial function marker. Dysfunctional levels were reported in all the studies investigating carnitine; however, the specific type of carnitine that was dysfunctional varied. Genetic profiles were the second most studied mitochondrial parameter. Six common pathways were proposed: metabolism, energy production, protein transport, mitochondrial morphology, central nervous system dysfunction and post-viral infection. Coenzyme Q10 was the most commonly investigated mitochondrial enzyme. Low levels of Coenzyme Q10 were consistently associated with fatigue. Potential targets for further investigation were identified as well as gaps in the current literature.