Understanding Immunomodulation and Managing Cancer Cachexia: A Narrative Review

Cancer cachexia is a multifactorial syndrome characterized by progressive muscle wasting, fat loss, and metabolic disruptions, commonly observed in cancer patients with advanced disease. It significantly impairs quality of life (QoL), reduces survival rates, and complicates treatment. The pathophysiology of cancer cachexia involves complex host-tumor interactions that lead to decreased appetite, metabolic shifts, and systemic inflammation. These alterations trigger muscle and fat degradation, making cachexia a critical component of cancer progression, particularly in patients with upper gastrointestinal, pancreatic, and lung cancers. Inflammatory markers, such as C-reactive protein, are key indicators of cachexia, and systemic inflammation plays a crucial role in the development of cachexia. Despite its severe impact, there are currently no standardized treatments for cancer cachexia. Clinical trials on immunomodulatory approaches have evaluated the beneficial potential of treating cancer cachexia. Immunomodulation, particularly through targeting multiple inflammatory cytokines, has shown benefit in mitigating cachexia-associated symptoms. Notably, the use of a newly identified immunomodulator, R-ketorolac, in animal models has demonstrated significant improvements in survival. Therefore, future research should focus on understanding the relationship between immune dysfunction and cachexia and developing personalized immunomodulation-based treatment strategies. Immunomodulators that repair destructive immune dysfunction hold promise for reversing cachexia symptoms, overall cancer treatment efficacy, patient survival, and QoL.