This paper outlines a systemic framework for understanding cancer cachexia, defining it as a tumor-driven collapse of whole-body homeostasis rather than a simple byproduct of malnutrition. It explains how malignancies function as signaling hubs, releasing a complex secretome of cytokines and vesicles that reprogram the host’s metabolic, immune, and neuroendocrine systems. This process triggers a maladaptive cascade across multiple organs, leading to profound skeletal muscle wasting, adipose tissue loss, and chronic inflammation. Consequently, patients suffer from functional decline, reduced treatment tolerance, and increased mortality. The authors advocate for multimodal therapeutic strategies and biomarker-guided trials that address these integrated circuits rather than isolated symptoms.

References:

• Zhang Y, Nipp R D, Janowitz T, et al. Cancer cachexia: A tumor-driven disorder of whole-body homeostasis[J]. Cancer Cell, 2026.