It was a tremendous privilege to work on this important research project with Young-Mee Kim. This project took more than 5 years to complete but we hope that in some small way, it will contribute to improving the health of cancer survivors.

Furthermore, Activin-A and other tumor factors could be similarly causing problems in other organs beyond the muscles by impairing the function of additional blood vessels.

This raises a broader question about cardiovascular or - more specifically - vascular health in cancer patients. Ensuring vascular health early on, even during the treatment of the cancer, could be very important for the preservation of muscle function.

Our discovery adds to the body of literature on muscle loss, cachexia, muscle fatigue in cancer survivors. We do not think that blood vessel dysfunction is the only cause of muscle issues in cancer, but it is one contributor that can be treated.

The good news is that we could prevent this by targeting Activin-A with an antibody. We also found that Activin-A suppresses the PGC1-alpha pathway in blood vessel endothelial cells. Gene therapy to upregulate PGC1-alpha in the blood vessels reversed the muscle loss!

One of the primary negative effects of Activin-A is the reduction of the number of functional blood vessels in the skeletal muscle

Through extensive molecular studies, we found that the molecule Activin-A is released into the blood by tumors, and this factor sets in motion a cascade of molecular signals in the blood vessel endothelial cells

This suggested that blood vessel problems in the muscle appear first, even during earlier stages of the tumor, and may actually cause worsening of the muscle loss.

In the mouse studies, we were able to perform a time experiment and we saw the the blood vessels in the muscles of mice bearing tumors showed a reduction of blood vessels in the muscle, and a loss of normal blood vessel function BEFORE muscle loss

The loss of blood vessels in the human muscles did not allow us to address what happened first. Did the cancer patients first lose their muscle mass, and then the muscle blood vessels wither away? Or did the blood vessel loss come first and actually make muscle loss worse?

We therefore specifically looked at the blood vessels in the muscles. Muscles of patients with cancer had reduced blood vessels, even when the tumor was far away from the muscles. The same was true for multiple mouse models of cancer.

Blood vessels supply nutrients and oxygen to all tissues - including muscles. Blood vessels also seem to do more than just serve as a supply pipeline, they appear to send signals or cues to various organs and tissues, and facilitate their regeneration

We wondered whether the tumors cause changes in the muscles which make it difficult for exercise and increased nutrition to work. This would explain why many cancer survivors have such a difficult time regaining their strength and building muscle mass

One of the biggest challenges that many cancer survivors face is the loss of muscle mass (cachexia) which emerges during the cancer, and often persists even after successful cancer treatment. For many survivors, attempts to increase food intake or exercise does not suffice

During the past couple of decades, new cancer treatments have substantially improved survival of #cancer patients. These successes now have to be accompanied by approaches to improve the #healthspan and quality of life of cancer survivors.

Thank you for sharing it!