Chemotherapy-Induced Weakness and Fatigue in Skeletal Muscle: The Role of Oxidative Stress

Significance: Fatigue is one of the most common symptoms of cancer and its treatment, manifested in the clinic through weakness and exercise intolerance. These side effects not only compromise patient's quality of life (QOL), but also diminish physical activity, resulting in limited treatment and increased morbidity. Recent Advances: Oxidative stress, mediated by cancer or chemotherapeutic agents, is an underlying mechanism of the drug-induced toxicity. Nontargeted tissues, such as striated muscle, are severely affected by oxidative stress during chemotherapy, leading to toxicity and dysfunction. Critical Issues: These findings highlight the importance of investigating clinically applicable interventions to alleviate the debilitating side effects. This article discusses the clinically available chemotherapy drugs that cause fatigue and oxidative stress in cancer patients, with an in-depth focus on the anthracycline doxorubicin. Doxorubicin, an effective anticancer drug, is a primary example of how chemotherapeutic agents disrupt striated muscle function through oxidative stress. Future Directions: Further research investigating antioxidants could provide relief for cancer patients from debilitating muscle weakness, leading to improved quality of life. Antioxid. Redox Signal. 15, 2543-2563.