Pancreatic Cancer Cachexia: Integrating Mechanistic Insights With Clinical Management.

Abstract

Cachexia is a multifactorial syndrome characterized by systemic inflammation, weight loss, and muscle wasting, affecting over 80% of patients with pancreatic cancer. It decreases treatment tolerance, quality of life, and survival. Yet, despite its well-recognized detrimental impact, cachexia remains underdiagnosed and undertreated in oncology clinics. This review synthesizes current understanding of pancreatic cancer cachexia with an emphasis on its complex pathophysiology involving inflammatory cytokines, tumor-derived catabolic factors, neuroendocrine disruption, and pancreatic insufficiency as advancing insight into these underlying mechanisms is driving the development of targeted therapies for cachexia. A narrative review of the literature was performed using PubMed, Embase, and Google Scholar to identify studies related to pancreatic cancer cachexia. Relevant peer-reviewed clinical trials, translational studies, and review articles focusing on pathophysiology, nutritional assessment, and management strategies were prioritized. Emerging therapeutic strategies targeting the underlying biology of cachexia, including growth differentiation factor-15 inhibition, inflammatory pathway blockade, and ghrelin receptor agonism, have demonstrated encouraging effects on weight, muscle preservation, appetite, and functional measures. Advances in nutritional assessment, body composition analysis, and biomarker development may further improve early detection and management. Pancreatic cancer cachexia should be recognized as an active and potentially modifiable process rather than an inevitable consequence of advanced disease. Earlier identification, multidisciplinary management, and emerging mechanism-based therapies may improve clinical outcomes and quality of life for patients with pancreatic cancer.