RESUMEN
Cancer-related fatigue (CRF) is a distressing side effect of cancer and treatment, affecting both patients during active treatment and survivors, negatively impacting quality of life. While its exact cause remains uncertain, various mechanisms such as immune dysfunction, HPA-axis dysfunction, and treatment toxicity are proposed. Inflammatory biomarkers of CRF have been explored in previous research, but non-inflammatory markers have not been comprehensively studied. This systematic review analysed 33 studies to identify non-inflammatory peripheral blood biomarkers associated with CRF. Promising markers included Hb, blood coagulation factors, BDNF, tryptophan, GAA, mtDNA, platinum, CA125, and cystatin-C. Inconsistent findings were observed for other markers like VEGF, leptin, and stress hormones. Most studies focused on adults. Research in pediatrics is limited. This review showed partial evidence for the inflammaging hypothesis (neurotoxicity due to neuro-inflammation) laying at the basis of CRF. Further research, especially in pediatrics, is needed to confirm this hypothesis and guide future biomarker studies.