Potential pathophysiological mechanism of cancer-related fatigue and current management

Cancer-related fatigue (CRF) is a common and crucial disease entity encountered by oncologists, which has been well defined in the International Classification of Diseases (10^th Revision). However, CRF is under recognized and difficult to treat. Cancer-related fatigue is frequently associated with advance-staged tumors and cancer therapies such as surgery, chemotherapy, and radiotherapy. Several studies have evaluated the use of drug interventions in CRF management but have conflicting results, depending on the population studied and the outcome measures used. Cancer-related fatigue is apparently associated with systemic inflammation that involves chronic activation/deregulation of the immune system. Traditional Chinese medicine (TCM) approaches may modulate immune functions. Botanical supplements are used worldwide to enhance immune responses and reduce pathogen-associated symptoms. This minireview includes an assessment of the efficacy of drug treatment in managing CRF, and a translational investigation of the anti-CRF activity of TCMs and their isolated components. In addition, we explored the possible mechanisms of action underlying TCM-mediated effects and their roles in immunomodulation. Furthermore, TCMs have demonstrated a spectrum of activities. For instance, TCMs inhibit cyclooxygenase and nitric oxide synthesis, promote free radical scavenging activity, and reduce inflammatory cytokines. In addition, evidence supports that TCMs restore impaired T cell functions, improve the M1/M2 macrophage ratio and cytokine balance, inhibit CD4⁺CD25⁺ regulatory T (Treg) cells, and suppress chemoradio-resistance in patients with cancer, which suggest TCMs are promising candidates for the development of new drug therapies against CRF.