gsk3b inhibitor Introduction Cancer related fatigue CRF

Introduction Cancer-related fatigue (CRF) is a common health concern among cancer survivors and patients with cancer; however, the mechanisms underlying the development and persistence of this symptom remain unclear. An overactivation of the gsk3b inhibitor may induce CRF, which is mediated by proinflammatory cytokines. Several studies have suggested inflammation has a crucial role in CRF, but data are limited with virtually no longitudinal data for such patients. We reviewed the currently available evidence regarding the potential pathophysiological mechanisms that cause CRF and regarding the management of CRF. The proposed biological and genetic mechanisms of CRF include cytokine dysregulation, hypothalamic–pituitary–adrenal axis dysfunction, 5-hydroxytryptophan (5-HT) neurotransmitter dysregulation, circadian rhythm disruption, alterations in adenosine triphosphate and muscle metabolism, and vagal afferent activation. In addition, studies have investigated genetic mechanisms, which include candidate genes, genome-wide scanning, and gene expression. Furthermore, several behavioral interventions have been evaluated regarding their ability to reduce CRF among patients with psychosocial risk factors. Recent data suggest that psychopharmacologic interventions may be effective in the management of CRF. Despite these promising findings, no clinical practice guidelines have been documented for the effective management of psychosocial risk factors in CRF. This review aims to elaborate the current understanding of CRF and to provide evidence-based advice to patients with CRF. Summary of key points of the minireview:
Cancer-related fatigue: an unmet medical need Advances in cancer treatment have improved survival rates and have prolonged the natural history of the disease. However, the improved survival rates are mitigated by the adverse effects associated with the therapeutic interventions, thereby resulting in a lower quality of life (QOL) for cancer survivors. Cancer-related fatigue (CRF) is a very commonly reported symptom with a prevalence rate of 59–100%, depending on the clinical status of the disease. Unlike the other types of fatigue caused by noncancerous factors, CRF is a complex symptom that is not resolved by resting. Cancer-related fatigue is multifactorial and is highly prevalent during various cancer treatments such as surgery and chemoradiotherapy and in patients with advanced cancers. In addition, CRF can develop as a chronic symptom in disease-free patients and in individuals who have been successfully treated for cancer. Cancer-related fatigue confers negative effects on mood, social relationships, daily activities, and overall QOL in patients with cancer. Therefore, translational research on CRF is particularly crucial because of its prevalence and because available treatments are limited and nonspecific. Cancer-related fatigue has been recently accepted as a diagnosis in the International Classification of Diseases 10th Revision—Clinical Modification. It may be characterized as a multidimensional phenomenon that develops in patients with cancer over time, and is associated with diminishing energy, mental capacity, and psychological condition (Table 1). According to the revised National Cancer Institute Common Toxicity Criteria, CRF is associated with lethargy, malaise, and asthenia. These classifications may improve awareness regarding fatigue and the reporting of such a condition. Despite the high prevalence of CRF, the mechanisms underlying its onset and persistence among patients with cancer have not been determined. Few studies have proposed the involvement of various biological mechanisms, although none of these studies reported a correlation between the assessed biological parameters (e.g., hematocrit, hemoglobin, albumin, and thyroid hormone levels) and CRF. A possible mechanism for the development of CRF is activation of the immune system in response to the tumor itself or to the treatments administered for the disease. In particular, the production of proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) are part of the host immune response to the tumor, tissue damage, or depletion of the immune cell subsets associated with cancer treatment. These cytokines confer a wide spectrum of peripheral and central effects that contribute to host defense, which include its effects on energy consumption.