A liver signaling pathway may explain why colorectal cancer weakens muscle and bone

Researchers at the University of Colorado Anschutz and Indiana University School of Medicine have discovered a signaling pathway that may explain why colorectal cancer leads to muscle and bone deterioration, particularly in advanced stages. This condition, known as cancer cachexia, weakens patients, hampers daily activities, and makes cancer treatment more challenging.

Published in Nature Communications, the study reveals that colorectal cancer cells communicate with the liver, triggering the production of a protein called IGFBP1. Once released into the bloodstream, IGFBP1 contributes to muscle and bone loss. Blocking IGFBP1 in laboratory and preclinical models helped maintain muscle and bone mass, enhancing muscle strength, even when cancer persisted.

The study's senior author, Andrea Bonetto, Ph.D., suggests this pathway offers a new way to address cancer-related wasting and a potential target to protect patients from its effects. Colorectal cancer cells produce FGF21, which signals the liver to produce more IGFBP1, which then enters the bloodstream and contributes to muscle and bone loss.

Elevated IGFBP1 levels were found in colorectal cancer patients, especially those with liver metastases. In laboratory and mouse models, blocking FGF21–IGFBP1 signaling preserved muscle, bone, and strength without consistently reducing tumor growth. The researchers emphasize that this approach could help protect patients from cancer-induced damage, enhancing their quality of life and survival, rather than directly attacking the tumor.

However, the research is still in its early stages, and further studies are needed to assess the safety and efficacy of targeting this pathway in humans.