Georgia Regents University Cancer Center, Georgia Regents University, Augusta, Georgia.
Department of Psychiatry and Health Behavior, Georgia Regents University, Augusta, Georgia.
Cancer. 2015 Jul 1;121(13):2129-36. doi: 10.1002/cncr.29302. Epub 2015 Feb 27.
Cancer-related fatigue (CRF) is a common complication of cancer and its treatment that can significantly impair quality of life. Although the specific mechanisms remain poorly understood, inflammation is now considered to be a distinct component of CRF in addition to effects of depression, anxiety, insomnia, and other factors. One key biological pathway that may link inflammation and CRF is indoleamine 2,3-dioxygenase (IDO). Induced by inflammatory stimuli, IDO catabolizes tryptophan to kynurenine (KYN), which is subsequently converted into neuroactive metabolites. Here we summarize current knowledge concerning the relevance of the IDO pathway to CRF, including activation of the IDO pathway in cancer patients and, as a consequence, accumulation of neurotoxic KYN metabolites and depletion of serotonin in the brain. Because IDO inhibitors are already being evaluated as therapeutic agents in cancer, the elucidation of the relationship between IDO activation and CRF in cancer patients may lead to novel diagnostic and clinical approaches to managing CRF and its debilitating consequences.
癌症相关性疲劳（CRF）是癌症及其治疗的常见并发症，可显著降低生活质量。尽管其具体机制仍不清楚，但炎症现在被认为是 CRF 的一个独特组成部分，除了抑郁、焦虑、失眠和其他因素的影响外。可能将炎症与 CRF 联系起来的一个关键生物学途径是吲哚胺 2,3-双加氧酶（IDO）。IDO 被炎症刺激诱导，将色氨酸代谢为犬尿氨酸（KYN），随后 KYN 转化为神经活性代谢物。在这里，我们总结了 IDO 途径与 CRF 相关的现有知识，包括 IDO 途径在癌症患者中的激活，以及由此导致的神经毒性 KYN 代谢物的积累和大脑中 5-羟色胺的耗竭。由于 IDO 抑制剂已被评估为癌症的治疗剂，因此阐明 IDO 激活与癌症患者 CRF 之间的关系可能会导致针对 CRF 及其进行性后果的新的诊断和临床方法。
