Why does cancer cause weight loss?

An international research team, led by La Trobe University, has uncovered the cause of the muscle-wasting disease cachexia in cancer patients. Their study, published in the journal Cell, brings hope to the large number of people — between 50 to 80% of those with solid tumours — who suffer from this wasting condition.

Cachexia is the unwanted loss of body weight that manifests as muscle loss, fat loss and overall metabolic imbalance. In advanced cachexia, cancer treatment is often withdrawn due to a person’s emaciated state; as a result, the condition is estimated to account for up to 30% of all cancer deaths.

“Cancer cachexia is such a serious complication of cancer and affects patients’ quality of life and ability to undergo punishing chemotherapy treatments,” said Dr Kate Murphy from the University of Melbourne, who collaborated on the new research. “There is no treatment for cachexia.”

It was always thought that cachexia was the result of cancer spreading and consuming the body, with loss of appetite and nutritional complications causing the body to waste away. But the researchers found that Fn14, a receptor on a cell’s membrane which is often present on cancer cells, can cause cachexia.

“Fn14 is normally absent on healthy and normal tissue, but it has some beneficial roles in the body, such as in the development of new tissue, like muscle, and also in the repair of damaged tissue,” said Dr Amelia Johnston from La Trobe University, the lead author on the study. “It’s normally switched on to do its job, and then it’s switched off when the job is finished.

“So what then happens in tumour setting is when Fn14 is present, it’s switched on. And it’s continually switched on. What this means is that the tumour cells send signals to the rest of the body, and it’s these signals that are responsible for causing the muscle wasting and the other symptoms of cachexia.”

While Dr Johnston said Fn14 has “been known to be involved in cancer”, she said it was a surprise to find out that it was also the cause of cachexia. By blocking Fn14, they could stop this wasting condition — regardless of the presence of a tumour.

The researchers have already started working on an antibody that is directed against Fn14. As noted by study co-author Nick Hoogenraad, a colleague of Dr Johnston’s, “If we can arrest cachexia it will give people extra time, improved quality of life, make them stronger and allow for therapy to continue.”

Dr Johnston spoke of the advantages of antibodies, stating, “Because antibodies are very specific to their target, this means treatment is less likely to come with the unwanted side effects of other therapies such as many chemotherapy drugs.” In fact, in some cases the antibody treatment has not only blocked cachexia, but also slowed the growth of the tumours.

The researchers are currently converting the antibody therapy into a treatment appropriate to trial in humans. “This is being done in collaboration with scientists at the Olivia Newton-John Cancer Research Institute,” said Dr Johnston. “After we have made an equivalent therapy for human use, clinical trials would be the next step.”