Tumors can destroy the blood vessels of muscles even when the muscles are nowhere close to the tumor. That is the key finding of a new study that my colleagues and I recently published in the journal Nature Cancer.
Muscle loss in cancer patients is a major health problem, but the exact causes of how precisely tumors affect muscles remain an active area of research.
Scientists in my lab were curious whether one explanation for the muscle loss in cancer patients could be that the cancer impairs the blood vessels that are necessary to supply nutrients and oxygen to muscles. Healthy blood vessels ensure that blood containing oxygen and nutrients is transported from the heart to all tissues and organs in the body, and then circulates back to the heart. Unhealthy blood vessels lose the ability to circulate sufficient blood and develop leaks, with nutrients seeping into the tissue prematurely and thereby cutting off the supply of nutrients to tissues that are further downstream.
To tackle this question, my colleagues and I worked with several other scientific research teams with expertise in advanced microscopy, cancer research and metabolism. We used animal models to study several kinds of tumors – lung cancer, skin cancer, colon cancer and pancreatic cancer. We consistently observed that the blood vessels in the muscles became fewer and leakier even before the muscle weakness set in.
We also found that tumors release a protein called Activin-A, which acts on blood vessels to cause the leakiness and, ultimately, loss of blood vessels in the muscle. When we used a gene therapy to restore blood vessel health by counteracting the effects of Activin-A, we were able to prevent the muscle loss.
So we examined the muscles of patients who had passed away because of cancer and found that the muscles of cancer patients contained fewer blood vessels than expected.
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Why Activin-A matters
Millions of cancer survivors struggle with muscle weakness, which can be so profound that they may have difficulties walking up a couple of flights of stairs or going shopping for groceries on their own.
Severe muscle weakness and muscle loss during cancer is called cancer cachexia, which occurs in up to 80% of patients with advanced cancer.
Recent research indicates that cachexia is far more common among cancer patients than previously suspected, with approximately half the patients who see their cancer doctor for the first time already showing signs of muscle weakness.
Importantly, cachexia can persist even after the cancer is successfully treated and cured. This can have a devastating impact on the quality of life for cancer survivors.
Our discovery that the loss of blood vessel function in the muscles occurs early on during the progression of the cancer suggests that fixing blood vessels in cancer patients and cancer survivors could be a new way to prevent or reverse cachexia.
The reasons for the muscle loss in cancer are complicated and involve poor nutrition due to loss of appetite and inflammation, which are initially caused by the tumor but persist even when the tumor is removed.
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What other research is being done
There are currently no treatments approved by the Food and Drug Administration for cachexia, but new therapies are on the horizon.
One such therapy is an antibody drug that targets the molecule GDF-15, a protein that is thought to suppress appetite.
Other studies are using a combination of targeted nutrition and exercise programs to help patients with cancer cachexia regain muscle mass and muscle strength.
All these studies suggest that we will need a combination of approaches to enhance exercise, nutrition, appetite, muscle regeneration and – as we propose – blood vessel health.
What’s next
We are now evaluating drugs and exercise programs that are known to improve blood vessel health. Repurposing these treatments that are traditionally designed for cardiovascular patients could be a rapid way to help cancer patients regain muscle strength.
We hope that our work highlights how important it is for cancer patients to receive comprehensive medical care, which includes improving cardiovascular health and overall quality of life.
The Research Brief is a short take on interesting academic work.
