By Admin at 4 Nov 2015, 12:14 PM

Muscle weakness can be a debilitating symptom of advanced cancer, leading to significantly reduced quality of life. Earlier this year, researchers discovered that such muscle weakness is often the result of tumor cells that have metastasized into bone.

This disrupts normal bone remodeling, including stimulating excessive osteoclast activity (osteoclasts are a type of bone cell that break down bone tissue). This, in turn, causes the release of growth factors stored in the bone matrix, fueling a “feed-forward vicious cycle of tumor growth in bone and bone destruction.”

The bone-derived growth factors, it was uncovered, also appear to act systemically to cause muscle weakness. Currently, there is no effective treatment for cancer-related muscle weakness, but a new study conducted by researchers from Indiana University and colleagues may change that.

They examined tumors from breast, prostate, lung and multiple myeloma cancers, which are examples of cancers that often spread to bone. They identified four molecular pathways that appear to be related to muscle weakness and were able to target the pathways using four different drugs, leading to improved muscle function in mice.

Specifically, inhibiting a growth factor called TGF-β, which is often released from bone as a result of metastasis-induced bone destruction, led to improved muscle function. In addition to working in the mouse model, inhibiting the growth factor also improved muscle function in human muscle samples from patients with cancer in bone.

Lead researcher Theresa Guise, M.D., the Jerry and Peggy Throgmartin Professor of Oncology at the IU School of Medicine and a researcher at the Indiana University Melvin and Bren Simon Cancer Center, told EurekAlert

"Advanced cancer often spreads to the bone and patients can have muscle weakness because of that. This weakness can severely reduce the quality of life in patients and increase the risk to fracture bone.

We previously showed that when cancer spreads and causes bone destruction it releases growth factors into the circulation. In the present study, we found that these factors can cause muscle weakness.

… In mice with cancer in bone, muscle weakness could be prevented by drugs that inhibit bone destruction or block the growth factor activity or stabilize calcium in the muscle. These drugs have the potential to prevent muscle weakness in patients with cancer in the bone."

Plans are in place to study the potential new therapies over the next few years. In the meantime, if you or a loved one is suffering from cancer-related muscle weakness talk with your physician about available options to help manage the symptoms and whether there are any related clinical trials available to join in your area.


Sources
Nature Medicine October 12, 2015
EurekAlert October 12, 2015
BoneKEy Reports May 13, 2015

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