[Multisystem interactive mechanisms of cancer-related fatigue: challenges of modern medical interventions and...

Cancer-related fatigue(CRF) is one of the most distressing symptoms in patients with malignant tumors, characterized by persistent physical and mental exhaustion that is not alleviated by rest, significantly impairing patients' quality of life. The pathogenesis of CRF involves complex multi-system interactions, which can be summarized as neuro-immune dysregulation and skeletal muscle and mitochondrial dysfunction. Currently, modern medicine faces significant challenges in the clinical management of CRF, including unclear mechanisms of pharmacological interventions, insufficient evidence-based support, and notable side effects. Although non-pharmacological interventions(such as exercise therapy, cognitive behavioral therapy, and light therapy) have been proven effective, they are limited by inadequate standardization of implementation protocols, low patient adherence, and difficulties in sustaining long-term therapeutic effects. In contrast, traditional medicine, especially TCM, demonstrates unique advantages in the holistic regulation of CRF. Chinese herbal medicine offers distinct strengths through multi-target modulation(such as immune regulation, HPA axis modulation, and energy metabolism). The strategy of treatment based on syndrome differentiation(such as replenishing Qi and nourishing blood, strengthening the spleen, and tonifying the kidney) has achieved remarkable clinical outcomes. Non-pharmacological TCM therapies(such as moxibustion and Tuina) have also been shown to alleviate CRF symptoms. This article systematically reviews the multi-system interactive mechanisms underlying CRF and the challenges in modern medical interventions, with a focused discussion on the integrative application prospects of TCM in CRF treatment. It aims to provide a theoretical foundation and research directions for establishing a new comprehensive treatment model that integrates TCM and western medicine, emphasizing individualized and precision-based approaches.