Figure 1. The involvement of an expanded tumor macroenvironment in cancer cachexia.

The illustration depicts the original tumor macroenvironment in cancer cachexia described as the Cori cycle involving metabolite and signaling crosstalks between tumor, adipose, skeletal muscle, and liver tissues leading to catabolism (atrophy and lipolysis) and weight loss (unshaded region). More recently, signaling axes have been identified originating from different tumor types that reveal an expanded tumor macroenvironment in cancer cachexia involving crosstalk between brain to muscle; bone to muscle; and gut microbiota to adipose and muscle that contributes to tissue catabolism (shaded region).