Loss of body weight due to progressive muscle wasting with or without the loss of fat stores is seen in many cancer patients. It is caused by cachexia, a metabolic disorder. Cachexia is seen in 50-80 per cent of patients with advanced solid tumours and during the terminal stages of many chronic illnesses.
In the case of cancer patients, it reduces patient survival and ability to tolerate intensive chemotherapy. As a result, the condition severely restricts treatment options for people with late-stage cancers and may account for about 25 per cent of all cancer deaths. Unlike in mice, in humans, cachexia “usually progresses slowly, with an average loss of 5 per cent body mass over 12 months.”
Now, for the first time, researchers know what is causing cachexia. Fn14, a receptor on a cell’s membrane which is often present on cancer cells, causes cachexia. With the identification of the receptor responsible for cachexia, there is hope that weight loss can be stopped by blocking Fn14, regardless of the presence of a tumour.
The results of a study to understand the role of Fn14 receptor were published today (September 11) in the journal Cell by Amelia J. Johnston, the senior author from La Trobe University, Melbourne, Australia.
Fn14 has been known to be involved in cancer, so when the researchers expressed Fn14 on tumours, they were surprised to see severe weight loss and overall decline in health of mice. While tumours can even suppress appetite, loss of weight in the animals was not due to a tumour effect on feeding, the paper notes.
To ascertain the role of Fn14 in causing cachexia, the researchers used an antibody that was specific to Fn14 receptor. The antibody prevented the Fn14 from causing muscle mass loss from all of the major skeletal muscles in mice. The antibodies helped in retaining body mass, muscle mass, adipose tissue and also bring about marginal effect on tumour growth.
“Muscle function, along with fat stores, was also retained in the antibody-treated mice,” they write. The study has brought them a step closer in finding a way to prevent or stop cachexia; stoping cachexia may have implications in fighting cancer, too.
“The Fn14 antibodies may be a promising approach to treat cachexia, thereby extending lifespan and improving quality of life for cancer patients,” they write.
While the mechanism of action remains unclear, “there is no doubt that tumour-localized Fn14 induces cachexia in the models presented here, and antibody therapy ablates this condition,” they stress.
Till date, it was always thought that weight-loss was due to cancer spreading and consuming the body, with loss of appetite and nutritional complications causing the body to waste away. As a result, all attempts to cure cachexia by increasing appetite or nutrition have proved unsuccessful.
“Our findings are a positive step in the right direction for developing a treatment for cancer-cachexia. We are currently converting the antibody therapy into a treatment appropriate to trial in humans,” Dr. Johnston said in a release.
“A therapy that directly targets cancer-associated cachexia is desperately needed. We have demonstrated that anti-Fn14 reagents present a tangible treatment and must now be tested for their efficacy in cancer patients presenting with hallmarks of cachexia,” they conclude.
