Liver protein linked to muscle and bone loss in colorectal cancer, in lab and mice

A cancer signal travels farther than the tumor. Researchers at the University of Colorado Anschutz and Indiana University School of Medicine found that colorectal cancer cells can prompt the liver to release IGFBP1, a protein that contributes to muscle and bone loss. In laboratory and mouse studies, blocking it preserved both tissues and improved muscle strength.

The relay begins with FGF21, a protein produced by the cancer cells. It signals the liver to make more IGFBP1, which then enters the bloodstream. In experiments, IGFBP1 made muscle cells shrink and increased the development of cells involved in breaking down bone. In people with colorectal cancer, IGFBP1 levels were about twice as high as in healthy individuals, particularly when the cancer had spread to the liver.

The researchers describe a potential target for cancer cachexia, the wasting condition that can leave patients weak, limit everyday activities and make treatment harder to tolerate. Blocking IGFBP1 in laboratory and preclinical colorectal cancer models preserved more muscle and bone and produced greater strength, but it did not consistently reduce the amount of cancer.

So what changes in practice? Not yet a treatment, but a possible second line of defense: protecting the body while oncology teams continue targeting the tumor. Preserving muscle and bone could help patients remain stronger, more mobile and better able to tolerate treatment, although that benefit still needs to be demonstrated in people.

The main uncertainty is safety. FGF21 and IGFBP1 also play roles in normal metabolism, so blocking the pathway could affect functions beyond cancer-related wasting. Andrea Bonetto, the study's senior and co-corresponding author, says the next challenge is determining whether the signal can be targeted safely in patients. The findings were published in Nature Communications.