Understanding Immunomodulation and Managing Cancer Cachexia: A Narrative Review

Abstract: Cancer cachexia is a complex, multifactorial syndrome commonly seen in patients with advanced cancer. Characterized by progressive weight loss, muscle and fat wasting, systemic inflammation, and impaired immune responses, cachexia involves a dysregulated host-tumor interaction that alters metabolism and disrupts immune homeostasis. Unlike malnutrition, cancer cachexia significantly affects the quality of life (QoL), treatment response, and overall survival. Despite its clinical relevance, particularly in cancers such as pancreatic, lung, liver, and gastrointestinal malignancies, there is a lack of standardized, effective treatments, and the immunological mechanisms underlying cachexia are not yet fully understood. Therefore, a better understanding of not just the pathways but also the underlying factors that influence the occurrence of cancer cachexia is vital to develop targeted therapeutic strategies. This review aims to explore the pathophysiology of cancer cachexia and also highlight a few key factors influencing cachexia occurrence, such as age, gender, comorbidities, cancer type, and stage. It also evaluates current and emerging therapeutic approaches, potential immunomodulatory strategies, and identifies the gaps in research and proposes future directions for the personalized management of cancer cachexia. Therapeutic strategies such as exercise, nutritional support, ghrelin agonists, myostatin inhibitors, and anti-inflammatory agents offer partial benefits. Promising immunomodulatory approaches, including agents like R-ketorolac and gut microbiota-targeted therapies, demonstrate potential in some clinical studies. However, cancer cachexia necessitates a multimodal treatment framework incorporating immunological insights and integrating physical activity and nutritional support along with pharmacological intervention, personalized as per the patients’ needs.